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RecruitingNCT04628767Updated Nov 12, 2026

Testing the Addition of MEDI4736 (Durvalumab) to Chemotherapy Before Surgery for Patients With High-Grade Upper Urinary Tract Cancer

A Phase 2/3 interventional study of Biopsy Procedure and Biospecimen Collection in Renal Pelvis and Ureter Urothelial Carcinoma, sponsored by National Cancer Institute (NCI). Recruiting at 258 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-11-12.

Sponsored by National Cancer Institute (NCI) · Phase 2/3, Interventional, and Treatment

From the registry’s dates

  • Started Nov 2021; still recruiting 5 years later.
Updated Nov 9, 2026Site recruiting status changed3 sites added+1 moreGo to Updates ↓

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Phase
Phase 2/3
Study type
Interventional
Enrollment
131
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This phase II/III trial compares the effect of adding durvalumab to chemotherapy versus chemotherapy alone before surgery in treating patients with upper urinary tract cancer. Immunotherapy with monoclonal antibodies, such as durvalumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Chemotherapy drugs, such as methotrexate, vinblastine, doxorubicin, cisplatin, and gemcitabine work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Durvalumab in combination with chemotherapy before surgery may enhance the shrinking of the tumor compared to chemotherapy alone.

Read the detailed description

PRIMARY OBJECTIVES:

I. To compare event-free survival (EFS) between patients with upper tract urothelial cancer (UTUC) randomized to neoadjuvant accelerated methotrexate, vinblastine, Adriamycin, cisplatin (aMVAC) alone or in combination with durvalumab. (Cisplatin eligible patients [Arms A and B]) II. Evaluation of pathologic complete response at radical nephroureterectomy (RNU) (pathologic complete response [pCR], ypT0N0/Nx). (Cisplatin ineligible patients [Arm C]).

SECONDARY OBJECTIVES:

I. To assess pathologic complete response (pCR) at surgery. (Cisplatin eligible cohort) II. Event-free survival (EFS) will be evaluated for the cisplatin ineligible cohort as a secondary endpoint. (Cisplatin ineligible cohort) III. Overall survival in all, and by post chemotherapy response (ypT0N0, yp =\< T1N0, yp >= T2Nany). (All patients) IV. To evaluate disease-free survival (DFS) in each arm of the trial separately. (All patients) V. To evaluate cancer-specific survival of patients in each arm of the trial separately. (All patients) VI. To evaluate renal function outcomes following systemic treatment and following surgery ([RNU) in each arm of the trial separately. (All patients) VII. To evaluate safety and tolerability of neoadjuvant aMVAC alone or in combination with durvalumab prior to RNU. (All patients)

OUTLINE: Patients eligible for cisplatin are randomized to Arms A or B. Patients ineligible for cisplatin are assigned to Arm C.

ARM A: Patients receive durvalumab intravenously (IV) over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

ARM B: Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

ARM C: Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery.

Patients also undergo tissue biopsy and blood sample collection on study, and computed tomography (CT) or magnetic resonance imaging (MRI) throughout the trial.

After completion of study treatment, patients are followed up within 30 days and then every 3-6 months for up to 5 years from study entry.

02

Conditions studied

  • Renal Pelvis and Ureter Urothelial Carcinoma
03

In context

Lead sponsor

National Cancer Institute (NCI) is the lead sponsor of 3,556 studies on the registry; 336 are open to participants now.

Of its 412 completed or terminated interventional studies of FDA-regulated products, 374 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

Counted across the registry records on this site, refreshed daily.

04

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

Eligibility criteria

Inclusion Criteria:

  • STEP 1 REGISTRATION AND RANDOMIZATION
  • Patients must be >= 18 years of age
  • Patient must have the ability to understand and the willingness to sign a written document. Patients with impaired decision-making capacity (IDMC) who have a legally authorized representative (LAR) or caregiver and/or family member available will also be considered eligible

  • Patient must have a diagnosis of high grade upper tract urothelial carcinoma expected within 14 weeks (98 days) prior to registration/randomization with one of the following:

    • (gold standard, preferred) and either upper urinary tract mass on cross-sectional imaging or tumor directly visualized during upper urinary tract endoscopy

    • High grade cytology and clinically estimated invasive upper urinary tract mass on cross-sectional imaging (e.g., including presence of tumor-related hydronephrosis) or tumor directly visualized during upper urinary tract endoscopy

      • NOTE: Universal histologic testing of UTUC with additional studies, such as immunohistochemistry and/or microsatellite instability, is strongly recommended to identify patients with high probability of Lynch-related or other germline mutation related cancers whom clinicians should refer for genetic counseling and germline testing (this is not required for eligibility)

        • Due to the anatomy of upper urinary tract and lack of muscularis propria, pathologic evidence of cT2 on biopsy is usually not possible
  • Patients must not have any component of small cell/neuroendocrine carcinoma. Other histologic subtypes (variants) are permitted provided the half or predominant (>= 50%) subtype is conventional urothelial carcinoma
  • Leukocytes >= 3,000/mcL (obtained =\< 14 days prior to registration/randomization)
  • >= 100,000/mcL (obtained =\< 14 days prior to registration/randomization)
  • Total =\< 1.2 mg/dL (or ≤ 2 mg/dL for patients with Gilbert's disease)
  • (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =\< 2 x institutional (obtained =\< 14 days prior to registration/randomization)

  • (Hgb) >= 9 g/dL (obtained =\< 14 days prior to registration/randomization)

    • NOTE: Packed red blood transfusion is allowed to achieve this parameter as per treating investigator
  • Patients must not be pregnant or breast-feeding due to the potential harm to an unborn fetus and possible risk for adverse events in nursing infants with the treatment regimens being used. All patients of must have a blood test or urine study within 14 days prior to registration to rule out pregnancy. A patient of childbearing potential is defined as any patient, regardless of whether they have undergone tubal ligation, who meets the following criteria: 1) has achieved menarche at some point, 2) has not undergone a hysterectomy or bilateral oophorectomy; or 3) has not been naturally (amenorrhea following cancer therapy does not rule out childbearing potential) for at least 24 consecutive months (i.e., has had menses at any time in the preceding 24 consecutive months)
  • Patients of childbearing potential and sexually active patients must not expect to conceive or father children, either by using accepted and effective method(s) of or by abstaining from sexual intercourse from the time of registration, while on study treatment and for at least 6 months after the last dose of protocol treatment

  • Patients must have no evidence of disease or clinically enlarged regional lymph nodes (>= 1.5 cm short axis) on imaging required within 28 days prior to registration (Non-regional findings >=1.5 cm short axis that in the opinion of the investigator are not concerning for involvement based on radiographic characteristics, chronicity, avidity on positron emission tomography (PET) scan or other imaging or other criteria can be eligible based on investigator discretion).

    • NOTE: Patients with elevated alkaline phosphatase, calcium or suspicious bone pain/tenderness can also undergo baseline bone scan to evaluate for bone metastasis at the discretion of local provider.

  • Patient must meet below criteria for prior/current history:

    • Non-urothelial cancer malignancy history:

      • Patient must not have another active (or within two years) second malignancy other than resected non-melanoma skin cancers, resected in situ breast, cervical or other in situ carcinoma, and either clinically insignificant per the investigator (e.g. =\< Gleason 3+4) on active surveillance (or watchful waiting) or previously treated prostate cancer with no rising prostate specific antigen (PSA) and no plan to treat

        • NOTE: Patients with prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the regimen are eligible for this trial.

      • Urothelial cancer malignancy history:

        • Patient may have a history of resectable urothelial cancer as long as patients meet one of the following:
        • T0, Ta or Tis at any time
        • T1-4a N0 and no evidence of disease (NED) for more than 2 years from the latest therapy [e.g., radical surgery, transurethral resection of bladder tumor (TURBT), radiation, chemotherapy ( or adjuvant, or with radiation)]. Prior systemic is not allowed.
        • Patient with history of >= pT4b, N+, and/or M1 UC is not eligible.
        • NOTE: Patients in whom concomitant or prior bladder/urethra predominant (>= 50%) urothelial carcinoma have been surgically resected and demonstrated to be only Ta or carcinoma in situ (CIS) (\< cT1 N0) are eligible regardless of time elapsed
  • Patient must not have any uncontrolled illness including, but not limited to, ongoing or active infection including tuberculosis (clinical evaluation that includes clinical history, physical examination and radiographic findings, and tuberculosis testing in line with local practice), symptomatic congestive heart failure (CHF), myocardial infarction (MI) or unstable angina pectoris, significant uncontrolled cardiac arrhythmia, liver cirrhosis, interstitial lung disease, or psychiatric illness/social situations in the three months prior to registration that would limit compliance with study requirements
  • Patient must not have received prior radiation therapy to >= 25% of the bone marrow for other diseases

  • Patient must not have received prior systemic anthracycline therapy

    • NOTE: Patients who have received prior intravesical therapy at any time for non-muscle invasive urothelial carcinoma of the bladder are eligible
  • Patient must not have either history of or active disease requiring therapy within 2 years prior to registration/randomization or any history of inflammatory bowel disease (inflammatory bowel disease [IBD], e.g. ulcerative colitis, or Crohn's disease), neuromuscular autoimmune condition, immune-related pneumonitis or interstitial lung disease. Patients with well-controlled hyper/hypothyroidism, celiac controlled by diet alone, diabetes mellitus type I, vitiligo, alopecia, psoriasis, eczema, lichen planus, or similar skin/mucosa condition are eligible

  • Patient must not be on or have used immunosuppressive medication within 14 days prior to the first dose of durvalumab. The following are exceptions to this criterion and are allowed:

    • Intranasal, inhaled, intra-auricular, topical , or local steroid injections (e.g. intra-articular injection
    • Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or its equivalent at the time of enrollment
    • Steroids as pre-medications for reactions (e.g. computed tomography [CT] pre-medication)

  • (HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months prior to registration/randomization are eligible for this trial

    • NOTE: These patients must be stable on their anti-retroviral regimen with evidence of at least two undetectable viral loads within the past 6 months on the same regimen; the most recent undetectable viral load must be within the past 12 weeks. They must have a of greater than 250 cells/mcL over the past 6 months on this same anti-retroviral regimen and must not have had a CD4 count \< 200 cells/mcL over the past 2 years, unless it was deemed related to the cancer and/or chemotherapy induced bone marrow suppression. They must not be currently receiving prophylactic therapy for an opportunistic infection and must not have had an opportunistic infection within the past 6 months
    • NOTE: For patients who have received chemotherapy in the past 6 months, a CD4 count \< 250 cells/mcL during chemotherapy is permitted as long as viral loads were undetectable during this same chemotherapy. They must have an undetectable viral load and a CD4 count >= 250 cells/mcL within 7 days of registration/randomization

  • For patients with evidence of chronic virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated

    • NOTE: Testing for HIV, hepatitis B or is not required unless clinically indicated
  • Patients with a history of hepatitis C virus (HCV) infection must have been treated and have undetectable viral load. For patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
  • Patients with known history or current symptoms of cardiac disease, or history of treatment with cardiotoxic agents, should have a clinical risk assessment of cardiac function using the Functional Classification. To be eligible for this trial, patients should be class 2B or better
  • Patient must not have received within 30 days prior to the first dose of durvalumab, while on protocol treatment and within 30 days after the last dose of durvalumab

  • Patient must not have had a major surgical procedure within 28 days prior to registration/randomization

    • NOTE: Cystoscopy/ureteroscopy/TURBT, stent placement or nephrostomy tube is not considered major surgery
  • Patient must not have history of allogenic organ transplantation
  • Patient must have a body weight of > 30 kg
  • Patient must have of >= 12 weeks

  • Patient must have > 15 ml/min as estimated by Cockcroft-Gault formula or (GFR) > 15 ml/min/1.73m\^2 within 28 days prior to registration/randomization

    • NOTE: Patients will be assigned to cisplatin-ineligible and cisplatin-eligible cohorts based on their creatinine clearance, (ECOG) performance status, and grade (if any) of peripheral neuropathy and/or hearing loss in keeping with recommended cisplatin . Patients who are cisplatin-eligible will be randomized to either Arm A or Arm B and patients who are cisplatin-ineligible will be registered to Arm C

      • Patients that meet any of the following four criteria will be registered to the cisplatin-ineligible Arm C if they meet other eligibility criteria:

        • Creatinine clearance > 15 ml/min and =\< 50 ml/min (estimated by Cockcroft-Gault formula) or GFR > 15ml/min/1.73m\^2 and ≤ 50 ml/min/1.73 m\^2
        • Hearing loss >= 3
        • Neuropathy >= 2
        • ECOG performance status 2
      • In addition, the patient must have an (ANC) >= 1,000/mcL obtained =\< 14 days prior to registration

      • Patients that meet all of the following four criteria will be randomized to the cisplatin-eligible Arm A or Arm B:

        • Creatinine clearance > 50ml/min (estimated by Cockcroft-Gault formula) or GFR > 50ml/min/1.73m\^2
        • ECOG performance status 0-1
        • Hearing loss grade 0-2
        • Neuropathy 0-1
      • In addition, the patient must have an absolute neutrophil count (ANC) >= 1,500/mcL obtained =\< 14 days prior to randomization
      • Also, the patient must have (LVEF) >= 50% by (either multigated acquisition scan [MUGA] or 2-D echocardiogram) obtained within obtained within 28 days prior to randomization
Terms in these criteria, in plain language(33)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

Biopsy and archival tissue

A biopsy takes a small piece of tissue to examine. “Archival tissue” is a sample already taken, for example at diagnosis, and kept by the hospital.

Whether a stored sample will do depends on when it was taken, how much there is and what the study needs. Ask whether the study accepts your stored sample or needs a new biopsy.

Platelets

Blood cells that help blood clot. Too few raises the risk of bleeding and bruising. A usual adult range is about 150–400 × 10⁹/L (150,000–400,000 per µL); each lab has its own reference range.

Bilirubin

A yellow substance made when red blood cells are broken down, which the liver clears. A high level can mean a problem with the liver or the bile ducts.

Criteria often allow more for people with Gilbert’s syndrome, a harmless inherited condition that raises bilirubin.

ALT and AST (liver enzymes)

Two enzymes measured in a routine blood test of the liver. Higher levels can mean the liver is under strain or damaged. SGPT and SGOT are older names for ALT and AST.

Criteria usually give a limit as a multiple of the upper limit of normal (ULN), often higher when cancer has spread to the liver.

ULN (upper limit of normal)

The top of the normal range for a blood test, as set by the laboratory that runs it. Each lab prints its own range next to your result.

“≤ 2.5 × ULN” means the result can be up to two and a half times that top value.

Hemoglobin (Hb)

The protein in red blood cells that carries oxygen. A low level is anaemia, which can cause tiredness and breathlessness. Measured in g/dL or g/L (9 g/dL is 90 g/L).

Childbearing potential

Able to become pregnant: from the first period until menopause, unless permanently unable to through surgery (removal of the womb, or of both ovaries or both fallopian tubes).

Criteria for people of childbearing potential usually ask for a negative pregnancy test and for contraception during the study and for a time after it.

Postmenopausal

Periods have stopped for good: usually no period for 12 months in a row without another medical reason, sometimes confirmed by a blood test (FSH).

Contraception

Ways of preventing pregnancy. “Highly effective” methods fail less than 1% of the time a year when used correctly — for example an IUD or an implant.

Criteria usually say which methods count and how long to keep using them after the last dose, sometimes for male participants too. Some studies accept a partner’s vasectomy if it was confirmed successful and that person is the participant’s only sexual partner.

Metastases

Cancer that has spread from where it began to other parts of the body. “Metastatic” cancer is cancer that has spread this way.

Cancer (malignancy)

Malignancy means cancer. Criteria about another or earlier malignancy ask whether you have had a different cancer, usually within a set number of years.

Some are commonly allowed, such as treated skin cancers other than melanoma and early cancers removed completely — check the exceptions this study lists.

Investigational drug or device

A drug or device being studied in a clinical trial.

It may be new, or already approved and being studied for another use, dose or form. Criteria often leave out people who took part in another study of one within a recent period, commonly 30 days or five half-lives.

Adjuvant and neoadjuvant

Neoadjuvant treatment is given before the main treatment (usually surgery), often to shrink a tumour. Adjuvant treatment is given after it, to lower the chance of the cancer coming back.

PD-1, PD-L1 and checkpoint inhibitors

PD-1, PD-L1 and CTLA-4 are proteins that act as brakes on the immune system. Checkpoint inhibitors, such as pembrolizumab or nivolumab, block them so the immune system can attack a cancer.

PD-L1 can also be measured in a tumour sample. Some scores count stained tumour cells only (TPS); others also count certain immune cells (CPS). The study names the score and the minimum it uses.

Clinically significant

Judged by the study doctor to matter for your health or for the study. It is a doctor’s decision, so ask the study team if you are unsure whether something counts.

Autoimmune disease

A condition in which the immune system attacks the body’s own tissues, such as rheumatoid arthritis, lupus, psoriasis, type 1 diabetes or inflammatory bowel disease.

Immunotherapy studies often leave out active autoimmune disease, and some name exceptions, such as thyroid disease on replacement hormone. Check the exceptions this study lists.

Immunosuppression

A weakened immune system. It can come from an illness, such as HIV or some blood cancers, or from medicines that turn the immune system down, for example after an organ transplant or for an autoimmune disease; steroids at higher doses count.

Read whether the line is about a condition or about medicines, and which medicines and doses it means.

Corticosteroids (steroids)

Anti-inflammatory medicines such as prednisone, prednisolone and dexamethasone — not the anabolic steroids used for muscle.

Studies differ in what they allow: check which steroid medicines, routes (tablets, injections, creams, inhalers, eye drops) and doses this study accepts.

Hypersensitivity

An allergy, or another reaction of the immune system, to a substance. “Hypersensitivity to the study drug” means a known allergic reaction to it — not every side effect a medicine can have.

HIV

The human immunodeficiency virus, which weakens the immune system.

Many studies now accept people whose HIV is controlled on treatment, judged by the viral load and the CD4 count. Check the limits this study sets.

CD4 count

The number of CD4 cells, a type of white blood cell, in a given amount of blood. It is used to follow how well the immune system is doing in HIV.

Hepatitis B tests

Hepatitis B is a virus that infects the liver. These are separate tests: HBsAg positive usually means a current infection (a recent vaccination can briefly cause it too); total anti-HBc (HBcAb) positive means an infection now or in the past; HBV DNA measures how much virus is in the blood.

Some studies accept a past infection if HBV DNA is undetectable, sometimes with antiviral medicine during the study. Check what this study allows.

Hepatitis C tests

Hepatitis C is a virus that infects the liver. An HCV antibody test can stay positive after an infection has cleared (and is occasionally positive without one); an HCV RNA test shows whether the virus is there now.

After treatment, hepatitis C counts as cured when HCV RNA is still undetectable 12 weeks or more after the treatment ended. Studies often accept people cured this way.

NYHA class (heart failure)

The New York Heart Association’s four classes of how much heart failure limits physical activity.

I
No limits: ordinary activity causes no undue tiredness or breathlessness.
II
Slight limits: comfortable at rest, ordinary activity causes symptoms.
III
Marked limits: comfortable at rest, less than ordinary activity causes symptoms.
IV
Symptoms even at rest; any activity makes them worse.

Studies set their own limit — many outside heart failure leave out class III–IV, while heart failure studies may ask for a particular class. Check the class this study names.

Live vaccines

Vaccines made with a weakened form of the germ, such as measles–mumps–rubella (MMR), chickenpox and yellow fever. They can be risky when the immune system is weakened. Flu injections are not live; the nasal flu spray is.

Life expectancy

The study doctor’s estimate of how long someone is likely to live. Criteria use it so that people can stay in the study long enough for it to answer its question.

Creatinine clearance (CrCl)

How quickly the kidneys clear creatinine, a waste product, from the blood. A study may estimate it from a blood test with age, weight and sex (often by the Cockcroft–Gault formula), or measure it using blood and urine collected over a set time. Given in mL/min; higher is better.

GFR and eGFR (kidney filtering)

GFR (glomerular filtration rate) is how much blood the kidneys filter each minute. It is usually estimated from a blood test — eGFR, by formulas such as CKD-EPI or MDRD — and some studies ask for it to be measured directly instead. Usually given in mL/min/1.73 m².

Check the method, the units and the minimum the study states. A value of 90 or above is in the normal-or-high range, but kidney damage can show in other tests too.

ECOG performance status

A scale of how much an illness limits everyday activity. For people being assessed to join a study, scores run from 0 (fully active) to 4; lower is more active.

0
Fully active, no restrictions.
1
Limited in strenuous activity, but walking and able to do light work, such as housework or office work.
2
Walking and able to look after yourself, but unable to work; up and about more than half of waking hours.
3
Able to look after yourself only in part; in bed or a chair more than half of waking hours.
4
Unable to look after yourself at all; in bed or a chair all day.

Studies most often ask for 0–1 or 0–2. Your doctor gives the score; the WHO scale uses the same steps. The full scale also has 5, which records death.

Contraindication

A reason a treatment, test or procedure should not be given to a particular person, such as an allergy, another illness or a medicine they take.

Absolute neutrophil count (ANC)

The number of neutrophils, white blood cells that help fight infection, in a given amount of blood. Too few raises the risk of infection.

It is a count, not a percentage of the white cells. Limits are written in units that mean the same: ≥ 1.5 × 10⁹/L is ≥ 1,500 per mm³ (µL). Each lab has its own reference range.

LVEF (left ventricular ejection fraction)

The share of blood the heart’s main pumping chamber (the left ventricle) pushes out with each beat, measured by an echocardiogram (heart ultrasound) or a MUGA scan. About 50–70% is normal.

05

Study design

Phase
Phase 2 / Phase 3
Primary purpose
Treatment
Allocation
Randomized
Intervention model
Parallel assignment
Masking
None (open label)
Enrollment
131 participants (estimated)

Study arms

  • Experimental
    Arm A (durvalumab, chemotherapy)

    Patients receive durvalumab IV over 60 minutes on day 1 of chemotherapy cycles 1 and 3. Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Cisplatin · Procedure: Computed Tomography · Drug: Doxorubicin Hydrochloride · Biological: Durvalumab · Procedure: Magnetic Resonance Imaging · Drug: Methotrexate · Biological: Pegfilgrastim · Procedure: Therapeutic Conventional Surgery · Drug: Vinblastine Sulfate

  • Active comparator
    Arm B (chemotherapy)

    Patients also receive methotrexate IV over 2-3 minutes, vinblastine sulfate IV, doxorubicin IV, cisplatin IV over at least 2 hours on day 1. Treatments repeat every 14 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Drug: Cisplatin · Procedure: Computed Tomography · Drug: Doxorubicin Hydrochloride · Procedure: Magnetic Resonance Imaging · Drug: Methotrexate · Biological: Pegfilgrastim · Procedure: Therapeutic Conventional Surgery · Drug: Vinblastine Sulfate

  • Experimental
    Arm C (durvalumab, gemcitabine hydrochloride)

    Patients receive durvalumab IV over 60 minutes on day 1 and gemcitabine hydrochloride IV over 30 minutes on days 1 and 8. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity. Within 21- 60 days after completion of systemic treatment, patients with continued lack of radiographic presence of metastatic or unresectable disease undergo surgery. Patients also undergo tissue biopsy and blood sample collection on study, and CT or MRI throughout the trial.

    Procedure: Biopsy Procedure · Procedure: Biospecimen Collection · Procedure: Computed Tomography · Biological: Durvalumab · Drug: Gemcitabine Hydrochloride · Procedure: Magnetic Resonance Imaging · Procedure: Therapeutic Conventional Surgery

Interventions

  • ProcedureBiopsy Procedure

    Undergo tissue biopsy

    Also known as: Biopsy, BIOPSY_TYPE, Bx

  • ProcedureBiospecimen Collection

    Undergo blood sample collection

    Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

  • DrugCisplatin

    Given IV

    Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

  • ProcedureComputed Tomography

    Undergo CT

    Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

  • DrugDoxorubicin Hydrochloride

    Given Iv

    Also known as: 5,12-Naphthacenedione, 10-[(3-amino-2,3,6-trideoxy-alpha-L-lyxo-hexopyranosyl)oxy]-7,8, 9,10-tetrahydro-6,8,11-trihydroxy-8-(hydroxyacetyl)-1-methoxy-, hydrochloride, (8S-cis)- (9CI), ADM, Adriacin, Adriamycin, Adriamycin Hydrochloride, Adriamycin PFS, Adriamycin RDF, ADRIAMYCIN, HYDROCHLORIDE, Adriamycine, Adriblastina, Adriblastine, Adrimedac, Chloridrato de Doxorrubicina, DOX, DOXO-CELL, Doxolem, Doxorubicin HCl, Doxorubicin.HCl, Doxorubin, Farmiblastina, FI 106, FI-106, FI106, hydroxydaunorubicin, Rubex

  • BiologicalDurvalumab

    Given IV

    Also known as: Imfinzi, Immunoglobulin G1, Anti-(Human Protein B7-H1) (Human Monoclonal MEDI4736 Heavy Chain), Disulfide with Human Monoclonal MEDI4736 Kappa-chain, Dimer, MEDI 4736, MEDI-4736, MEDI4736

  • DrugGemcitabine Hydrochloride

    Given IV

    Also known as: dFdCyd, Difluorodeoxycytidine Hydrochloride, Gemcitabine HCI, Gemzar, LY 188011, LY-188011, LY188011

  • ProcedureMagnetic Resonance Imaging

    Undergo MRI

    Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

  • DrugMethotrexate

    Given IV

    Also known as: Abitrexate, Alpha-Methopterin, Amethopterin, Brimexate, CL 14377, CL-14377, Emtexate, Emthexat, Emthexate, Farmitrexat, Fauldexato, Folex, Folex PFS, Jylamvo, Lantarel, Ledertrexate, Lumexon, Maxtrex, Medsatrexate, Metex, Methoblastin, Methotrexate LPF, Methotrexate Methylaminopterin, Methotrexatum, Metotrexato, Metrotex, Mexate, Mexate-AQ, MTX, Novatrex, Rheumatrex, Texate, Tremetex, Trexeron, Trixilem, WR-19039

  • BiologicalPegfilgrastim

    Given via injection

    Also known as: Cegfila, Dulastin, Dyrupeg, Filgrastim SD-01, filgrastim-SD/01, Fulphila, Fylnetra, G-Lasta, Grasustek, HSP-130, Jinyouli, Neulasta, Neulastim, Neupopeg, Nyvepria, PEG-filgrastim, Pegcyte, Pegfilgrastim Biosimilar HSP-130, Pegfilgrastim Biosimilar Nyvepria, Pegfilgrastim Biosimilar Pegcyte, Pegfilgrastim Biosimilar PF-06881894, Pegfilgrastim Biosimilar Udenyca, Pegfilgrastim Biosimilar Ziextenzo, Pegfilgrastim-apgf, Pegfilgrastim-bmez, Pegfilgrastim-cbqv, Pegfilgrastim-cegf, Pegfilgrastim-dyru, Pegfilgrastim-fpgk, Pegfilgrastim-gras, Pegfilgrastim-jmdb, Pegfilgrastim-pbbk, Pegfilgrastim-pelg, Pegfilgrastim-pelm, Pegylated G-CSF, Pegylated GCSF, Pegylated Granulocyte Colony Stimulating Factor, Pelgraz, Pelmeg, PF-06881894, SD-01, SD-01 sustained duration G-CSF, Stimufend, Tripegfilgrastim, Udenyca, Ziextenzo

  • ProcedureTherapeutic Conventional Surgery

    Undergo surgery

  • DrugVinblastine Sulfate

    Given Iv

    Also known as: 29060 LE, 29060-LE, Exal, Velban, Velbe, Velsar, VINCALEUKOBLASTINE

06

What researchers measure

Primary outcomes

  1. Event-free survival (EFS) (Cisplatin eligible cohort: Arms A and B)

    Disease progression prior to surgery or omission of surgery due to unresectable tumors, muscle-invasive cancer or disease recurring outside of the bladder, urethra, or contralateral upper tract are considered as events for EFS.

    Time frame: From registration/randomization to the earliest of systemic recurrence outside urinary tract, cancer progression, or death from any cause, assessed up to 5 years

  2. Pathologic complete response (pCR) (Cisplatin ineligible cohort: Arm C)

    Will assess pathologic complete response at surgery (pCR, pT0N0/Nx) by local pathology review. Patients who drop out prior to surgery or who have unknown response status will be considered as non-responders.

    Time frame: At surgery

Secondary outcomes

  1. pCR (Cisplatin-eligible cohort: Arms A and B)

    Time frame: Up to 5 years

  2. EFS (cisplatin-ineligible cohort: Arm C)

    Will be characterized using the Kaplan-Meier method.

    Time frame: From registration/randomization to the earliest of systemic recurrence outside urinary tract, cancer progression, or death from any cause, assessed up to 5 years

  3. Overall survival (OS) (All Patients)

    OS will be evaluated by arm, post chemotherapy response (ypCR, stage yp =\< T1N0, yp \>= T2N0), as well as stage (ypCR and \> ypCR) within and across treatment arms. Will be estimated using Kaplan-Meier method.

    Time frame: From registration/randomization to death from any cause, assessed up to 5 years

  4. Urothelial cancer-free survival or disease-free survival (All Patients)

    A return of UTUC includes non-muscle invasive recurrences, pathologic T2 or higher muscle-invasive recurrences specifically in the urinary tract, metastatic disease outside the urinary tract, or death. Patients alive without documented UTUC will be censored at the date of last disease assessment.

    Time frame: From the date of surgery to the earlier of a return of upper tract urothelial cancer (UTUC) or death from any cause, assessed up to 5 years

  5. Cancer-specific survival (All Patients)

    Will be analyzed using Gray's method and cumulative incidence estimates will be reported.

    Time frame: From registration/randomization to death due to cancer; deaths due to other causes will be counted as competing events, assessed up to 5 years

  6. Renal function outcomes following systemic treatment and following radical nephroureterectomy (All Patients)

    The proportion of patients with renal insufficiency (creatinine \[CrCl\] \< 60 ml/min) post chemotherapy and post nephroureterectomy as well as the proportion of patients with renal function improvement (CrCl \< 60 ml/min at baseline and CrCl \>= 60 ml/min on study) will be reported along with exact binomial confidence intervals. The distribution of changes in renal function post chemotherapy as well as post surgery from baseline will also be reported. The analysis of renal function outcomes will be performed among patients who receive at least one dose of study therapy.

    Time frame: Post chemotherapy and post surgery

  7. Incidence of adverse events (All Patients)

    Toxicity will be evaluated in all treated patients.

    Time frame: Up to 30 days post surgery

07

Study locations

151 of 258 sites recruiting

Showing the first 100 of 258 sites. Choose a country and city above to see the rest.

08

References and documents

Individual participant data

Plan to share: Yes — NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.

Data sharing details ↗ · grants.nih.gov

No publications or documents are linked to this record.

09

Timeline

14 registry updates since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Nov 2021 (actual). Primary completion is estimated for Sep 2027, 70 months after the start.

How these figures are worked out, and which studies are left out of them.

Registered
Nov 13, 2020
First posted
Nov 16, 2020
StartActual
Nov 12, 2021
Primary completionEst.
Sep 30, 2027
CompletionEst.
Sep 30, 2027
Last update
Nov 12, 2026
What these dates mean
Start.
When the first participant enrolled; while estimated, when the study expects to open to recruitment.
Primary completion.
When the last participant was examined or treated to collect data for the study's main question, its primary outcome. A study that stopped early gives the date its data collection stopped.
Completion.
When the last participant's last visit took place, for every outcome, secondary ones and side effects included: the end of the study. Often later than primary completion, sometimes the same day.
Actual and Est.
Actual means the registry says the date has happened. Est. (estimated) is a date the sponsor plans or expects. It can still move, and the sponsor is expected to change it to actual once it has passed.
Sites
3 sites added, 2 sites removed. 7 sites changed recruiting status (5 now recruiting, 2 now suspended)
Show 7 sites
  • Cooperman Barnabas Medical Center · Livingston, United StatesSuspended→Recruiting
  • Rutgers Cancer Institute of New Jersey · New Brunswick, United StatesSuspended→Recruiting
  • Community Medical Center · Toms River, United StatesSuspended→Recruiting
  • OptumCare Cancer Care at Charleston · Las Vegas, United StatesRecruiting→Suspended
  • OptumCare Cancer Care at Fort Apache · Las Vegas, United StatesRecruiting→Suspended
  • Upper Valley Medical Center · Troy, United StatesSuspended→Recruiting
  • Johns Hopkins University/Sidney Kimmel Cancer Center · Baltimore, United StatesSuspended→Recruiting
Show 3 added (3 United States)
  • Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
  • Trinity Health IHA Medical Group-Alice Gustafson Center · Pontiac, United States
  • Minnesota Oncology - Edina · Edina, United States
Show 2 removed
  • West Virginia University Charleston Division · Charleston, United States
  • Newland Medical Associates-Pontiac · Pontiac, United States
across 13 updates, Sep 25, 2026 – Nov 9, 2026
Site contacts
Changed at 14 sites. See the sites
Show 14 sites
  • Cooperman Barnabas Medical Center · Livingston, United StatesContact added •••5200Contact added (no phone or email listed)
  • Rutgers Cancer Institute of New Jersey · New Brunswick, United StatesContact added •••7356Contact added (no phone or email listed)
  • Community Medical Center · Toms River, United StatesContact added L•••@rwjbh.org · •••8294Contact added (no phone or email listed)
  • West Virginia University Charleston Division · Charleston, United StatesContact none listed→C•••@vandaliahealth.org
  • UCHealth University of Colorado Hospital · Aurora, United StatesContact added •••0650Contact added (no phone or email listed)
  • UCHealth Highlands Ranch Hospital · Highlands Ranch, United StatesContact added •••0650Contact added (no phone or email listed)
  • UCHealth Lone Tree Health Center · Lone Tree, United StatesContact added e•••@jimmy.harvard.eduContact added (no phone or email listed)
  • OptumCare Cancer Care at Charleston · Las Vegas, United StatesContact removed r•••@sncrf.org · •••0013Contact removed (no phone or email listed)
  • OptumCare Cancer Care at Fort Apache · Las Vegas, United StatesContact removed r•••@sncrf.org · •••0013Contact removed (no phone or email listed)
  • Upper Valley Medical Center · Troy, United StatesContact added c•••@daytonncorp.org · •••2900Contact added (no phone or email listed)
  • Kingman Regional Medical Center · Kingman, United StatesContact added r•••@sncrf.org · •••0013Contact added (no phone or email listed)
  • UCHealth - Cherry Creek · Denver, United StatesContact removed e•••@jimmy.harvard.eduContact removed (no phone or email listed)
  • Johns Hopkins University/Sidney Kimmel Cancer Center · Baltimore, United StatesContact added j•••@jhmi.edu · •••8804Contact added (no phone or email listed)
  • East Jefferson General Hospital · Metairie, United StatesContact added e•••@lsuhsc.edu · •••3539Contact added (no phone or email listed)
across 12 updates, Sep 25, 2026 – Nov 9, 2026
Show all 14 updates
  1. Nov 9, 2026
    UCHealth - Cherry Creek is now Suspended
    Site contacts Changed at 1 site. See the sites
    Show the site
    • UCHealth - Cherry Creek · Denver, United StatesContact removed e•••@jimmy.harvard.eduContact removed (no phone or email listed)
  2. Nov 5, 2026
    East Jefferson General Hospital is now Recruiting
    Site contacts Changed at 1 site. See the sites
    Show the site
    • East Jefferson General Hospital · Metairie, United StatesContact added e•••@lsuhsc.edu · •••3539Contact added (no phone or email listed)
  3. Oct 30, 2026
    East Jefferson General Hospital is now Suspended
    Site contacts Changed at 1 site. See the sites
    Show the site
    • East Jefferson General Hospital · Metairie, United StatesContact removed e•••@lsuhsc.edu · •••3539Contact removed (no phone or email listed)
  4. Oct 28, 2026
    Kingman Regional Medical Center is now Recruiting
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Kingman Regional Medical Center · Kingman, United StatesContact added r•••@sncrf.org · •••0013Contact added (no phone or email listed)
  5. Oct 26, 2026
    2 sites added, 1 site removed
    Show 2 added (2 United States)
    • Trinity Health IHA Medical Group-Alice Gustafson Center · Pontiac, United States
    • Minnesota Oncology - Edina · Edina, United States
    Show 1 removed
    • Newland Medical Associates-Pontiac · Pontiac, United States
  6. Oct 13, 2026
    2 sites changed recruiting status (2 now recruiting)
    Show 2 sites
    • UCHealth - Cherry Creek · Denver, United StatesSuspended→Recruiting
    • Johns Hopkins University/Sidney Kimmel Cancer Center · Baltimore, United StatesSuspended→Recruiting
    Site contacts Changed at 2 sites. See the sites
    Show 2 sites
    • UCHealth - Cherry Creek · Denver, United StatesContact added e•••@jimmy.harvard.eduContact added (no phone or email listed)
    • Johns Hopkins University/Sidney Kimmel Cancer Center · Baltimore, United StatesContact added j•••@jhmi.edu · •••8804Contact added (no phone or email listed)
  7. Oct 8, 2026
    Kingman Regional Medical Center is now Suspended
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Kingman Regional Medical Center · Kingman, United StatesContact removed r•••@sncrf.org · •••0013Contact removed (no phone or email listed)
  8. Oct 7, 2026
    Upper Valley Medical Center is now Recruiting
    Site contacts Changed at 1 site. See the sites
    Show the site
    • Upper Valley Medical Center · Troy, United StatesContact added c•••@daytonncorp.org · •••2900Contact added (no phone or email listed)
  9. Oct 6, 2026
    2 sites changed recruiting status (2 now suspended)
    Show 2 sites
    • OptumCare Cancer Care at Charleston · Las Vegas, United StatesRecruiting→Suspended
    • OptumCare Cancer Care at Fort Apache · Las Vegas, United StatesRecruiting→Suspended
    Site contacts Changed at 2 sites. See the sites
    Show 2 sites
    • OptumCare Cancer Care at Charleston · Las Vegas, United StatesContact removed r•••@sncrf.org · •••0013Contact removed (no phone or email listed)
    • OptumCare Cancer Care at Fort Apache · Las Vegas, United StatesContact removed r•••@sncrf.org · •••0013Contact removed (no phone or email listed)
  10. Oct 5, 2026
    3 sites changed recruiting status (3 now recruiting)
    Show 3 sites
    • UCHealth University of Colorado Hospital · Aurora, United StatesSuspended→Recruiting
    • UCHealth Highlands Ranch Hospital · Highlands Ranch, United StatesSuspended→Recruiting
    • UCHealth Lone Tree Health Center · Lone Tree, United StatesSuspended→Recruiting
    Site contacts Changed at 3 sites. See the sites
    Show 3 sites
    • UCHealth University of Colorado Hospital · Aurora, United StatesContact added •••0650Contact added (no phone or email listed)
    • UCHealth Highlands Ranch Hospital · Highlands Ranch, United StatesContact added •••0650Contact added (no phone or email listed)
    • UCHealth Lone Tree Health Center · Lone Tree, United StatesContact added e•••@jimmy.harvard.eduContact added (no phone or email listed)
  11. Oct 2, 2026
    3 sites changed recruiting status (3 now suspended)
    Show 3 sites
    • UCHealth University of Colorado Hospital · Aurora, United StatesRecruiting→Suspended
    • UCHealth Highlands Ranch Hospital · Highlands Ranch, United StatesRecruiting→Suspended
    • UCHealth Lone Tree Health Center · Lone Tree, United StatesRecruiting→Suspended
    Site contacts Changed at 3 sites. See the sites
    Show 3 sites
    • UCHealth University of Colorado Hospital · Aurora, United StatesContact removed •••0650Contact removed (no phone or email listed)
    • UCHealth Highlands Ranch Hospital · Highlands Ranch, United StatesContact removed •••0650Contact removed (no phone or email listed)
    • UCHealth Lone Tree Health Center · Lone Tree, United StatesContact removed e•••@jimmy.harvard.eduContact removed (no phone or email listed)
  12. Oct 1, 2026
    1 site added, 1 site removed
    Show site
    • Vandalia Health/CAMC Institute for Academic Medicine · Charleston, United States
    Show 1 removed
    • West Virginia University Charleston Division · Charleston, United States
  13. Sep 29, 2026
    Site contacts Changed at 1 site. See the sites
    Show the site
    • West Virginia University Charleston Division · Charleston, United StatesContact none listed→C•••@vandaliahealth.org
  14. Sep 25, 2026
    3 sites changed recruiting status (3 now recruiting)
    Show 3 sites
    • Cooperman Barnabas Medical Center · Livingston, United StatesSuspended→Recruiting
    • Rutgers Cancer Institute of New Jersey · New Brunswick, United StatesSuspended→Recruiting
    • Community Medical Center · Toms River, United StatesSuspended→Recruiting
    Site contacts Changed at 3 sites. See the sites
    Show 3 sites
    • Cooperman Barnabas Medical Center · Livingston, United StatesContact added •••5200Contact added (no phone or email listed)
    • Rutgers Cancer Institute of New Jersey · New Brunswick, United StatesContact added •••7356Contact added (no phone or email listed)
    • Community Medical Center · Toms River, United StatesContact added L•••@rwjbh.org · •••8294Contact added (no phone or email listed)

From the registry record's own update history. This site started tracking changes on Sep 25, 2026; for anything earlier, see the record history on ClinicalTrials.gov ↗

10

Registry details

Key details

Study ID
NCT04628767
Lead sponsor
National Cancer Institute (NCI)
Responsible party
Sponsor
First posted
Nov 16, 2020
Start date
Nov 12, 2021
Primary completion
Sep 30, 2027 (estimated)
Completion
Sep 30, 2027 (estimated)
Last update
Nov 12, 2026

Study contacts

Jean H Hoffman-Censits
principal investigator · ECOG-ACRIN Cancer Research Group

Oversight

Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

Interested in this study?

Eligibility is decided by the study team. Share this record with your doctor or contact the team directly.

No contact was published for this record. The registry link below has the sponsor’s details.

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Discussion

Questions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.

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Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.

Studies of the drugs tested here: Cisplatin · Doxorubicin · Durvalumab · Methotrexate · Pegfilgrastim · Vinblastine

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