ClinicalTrials.gg
RecruitingNCT04205968Updated Oct 23, 2026

Ramucirumab and Paclitaxel or FOLFIRI in Advanced Small Bowel Cancers

A Phase 2 interventional study of Fluorouracil and Irinotecan in Metastatic Small Intestinal Adenocarcinoma, Stage III Small Intestinal Adenocarcinoma AJCC v8 and Stage IIIA Small Intestinal Adenocarcinoma AJCC v8, sponsored by SWOG Cancer Research Network. Recruiting at 536 sites in United States. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-10-23.

Sponsored by SWOG Cancer Research Network · Phase 2, Interventional, and Treatment

From the registry’s dates

  • Started Jun 2020; still recruiting 6 years 5 months later.
Updated Oct 23, 2026Site recruiting status changedGo to Updates ↓
Phase
Phase 2
Study type
Interventional
Enrollment
94
Allocation
Randomized
Ages
18 Years and older
Sex
All
01

Study summary

This phase II trial studies how well ramucirumab and paclitaxel or the FOLFIRI regimen (leucovorin calcium, fluorouracil, and irinotecan hydrochloride) work in treating patients with small bowel cancers that have spread extensively to other anatomic sites (advanced) or are no longer responding to treatment (refractory). Ramucirumab is a monoclonal antibody that attaches to and inhibits a molecule called VEGFR-2. This may restrain new blood vessel formation therefore reducing nutrient supply to tumor which may interfere with tumor cell growth and expansion. Drugs used in chemotherapy, such as paclitaxel, leucovorin calcium, fluorouracil, and irinotecan hydrochloride 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. Giving Ramucirumab plus paclitaxel or FOLFIRI, may be helpful in treating advanced or refractory small bowel cancers and may help patients live longer.

Read the detailed description

PRIMARY OBJECTIVES:

I. To evaluate whether progression-free survival (PFS) meets an efficacy threshold in patients with previously treated advanced small bowel adenocarcinoma who receive treatment with ramucirumab and paclitaxel or FOLFIRI.

II. If the stated threshold is met in both arms, to choose the better regimen with respect to progression free survival (PFS).

SECONDARY OBJECTIVES:

I. To assess overall response rate (ORR) [complete and partial, confirmed and unconfirmed] in the subset of patients with measurable disease treated with ramucirumab and paclitaxel or FOLFIRI in this patient population.

II. To assess overall survival (OS) in patients treated with ramucirumab and paclitaxel or FOLFIRI in this patient population.

III. To evaluate safety and toxicity associated with combination ramucirumab and paclitaxel treatment or FOLFIRI therapy in this patient population.

TRANSLATIONAL OBJECTIVES:

I. To explore the correlation of maximum decrease in CEA levels and time to maximum decrease in CEA levels with PFS, OS, and ORR.

II. To bank tissue and blood samples for other future correlative studies from patients enrolled on the study.

OUTLINE: Patients are randomized to 1 of 2 arms.

ARM I: Patients receive ramucirumab intravenously (IV) over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients completing study treatment are followed up every 8 weeks until disease progression. Once the disease has progressed, patients are followed up every 6 months for up to 3 years post registration.

02

Conditions studied

  • Metastatic Small Intestinal Adenocarcinoma
  • Stage III Small Intestinal Adenocarcinoma AJCC v8
  • Stage IIIA Small Intestinal Adenocarcinoma AJCC v8
  • Stage IIIB Small Intestinal Adenocarcinoma AJCC v8
  • Stage IV Small Intestinal Adenocarcinoma AJCC v8
03

In context

Lead sponsor

SWOG Cancer Research Network is the lead sponsor of 339 studies on the registry; 37 are open to participants now.

Of its 17 completed or terminated interventional studies of FDA-regulated products, 17 (100%) have results posted.

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

Inclusion criteria

  • Patients must have or cytologically confirmed small bowel adenocarcinoma. Ampullary adenocarcinomas are not eligible. Patients must have disease or locally advanced unresectable disease
  • are allowed if they have been adequately treated with radiotherapy or surgery and stable for at least 30 days prior to registration. Patients must be neurologically asymptomatic and without treatment for at least 7 days prior to registration
  • Patients must have measurable or non-. All scans needed for assessment of measurable disease must be performed within 28 days prior to registration. Non-measurable disease must be assessed within 42 days prior to registration. All disease must be assessed and documented on the Baseline Tumor Assessment Form
  • Patients must have progressed on prior therapy with a fluoropyrimidine and/or oxaliplatin, given either for metastatic/locally advanced disease or as therapy completed within the previous 12 months
  • Patients must have completed prior chemotherapy, immunotherapy, or radiation therapy at least 14 days prior to registration and all toxicity must be resolved to grade 1 (with the exception of grade 2 neuropathy) prior to registration. In (CTCAE) version 5.0 grade 2 sensory neuropathy is defined as "moderate symptoms; limiting instrumental activities of daily living (ADLs)"
  • Patients must have a complete medical history and physical exam within 28 days prior to registration
  • Patients must have a Zubrod performance status of 0 or 1
  • (ANC) >= 1,500/mcL (must be obtained within 28 days prior to registration)
  • >= 100,000/mcL (must be obtained within 28 days prior to registration)
  • A total =\< 1.5 x institutional limit normal (IULN) (must be obtained within 28 days prior to registration)
  • Serum glutamic-oxaloacetic transaminase () (aspartate aminotransferase [AST]) and serum glutamate pyruvate transaminase (SGPT) (alanine aminotransferase [ALT]) =\< 3.0 x IULN (or 5.0 x IULN if liver metastases are present) (must be obtained within 28 days prior to registration)
  • Serum creatinine =\< 1.5 x IULN OR calculated >= 40 mL/min (must have been obtained within 28 days prior to registration)
  • Patient must have urinary protein =\< 1+ on dipstick or routine urinalysis (UA) within 28 days prior to registration. If dipstick or routine analysis is >= 2+, a 24 - hour urine collections for protein must demonstrate \< 1000 mg of protein in 24 hours
  • Patients with a prior or concurrent 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
  • Patients must not have known dihydropyrimidine dehydrogenase deficiency
  • Patients must be offered the opportunity to participate in specimen banking
  • Patients must be informed of the investigational nature of this study and must sign and give written in accordance with institutional and federal guidelines

Exclusion criteria

Exclusion Criteria:

  • Patients must not have received prior treatment with irinotecan, taxane, or ramucirumab for small bowel adenocarcinoma
  • Patients must not have had major surgery within 28 days prior to registration, or minor surgery within 7 days prior to registration, and must not be planned for elective major surgery to be performed during protocol treatment
  • Patients must not be currently enrolled in or have discontinued within the last 28 days a clinical trial involving an product or non-approved use of a drug, or concurrently enrolled in any other type of medical research judged not to be scientifically or medically compatible with this study. Patients participating in surveys or observational studies are eligible to participate in this study
  • Patients must not be receiving chronic antiplatelet therapy, including dipyridamole or clopidogrel, or similar agents
  • Patient must not have a known bleeding diathesis
  • Patient must not have uncontrolled or poorly-controlled hypertension (> 160 mmHg systolic or > 100 mg HG diastolic for > 4 weeks) despite standard medical management
  • Patient tumors must not have known deficient mismatch repair (dMMR) or microsatellite instability high (MSI-H)
  • Patients must not be pregnant or nursing and must have had a negative pregnancy test within 4 weeks of starting treatment. Women/men of must have agreed to use an effective method. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures
  • Patients must not have an active infection requiring systemic therapy
  • Patient must not have liver dysfunctions manifested by either (1) B (or worse) or (2) cirrhosis (any degree) and a history of hepatic encephalopathy or ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
  • Patients must not have a history of deep vein thrombosis (DVT), pulmonary embolism (PE), or any other significant thromboembolism (venous port or catheter thrombosis or superficial venous thrombosis are not considered "significant") during the 90 days prior to registration
  • Patients must not have experienced any arterial thrombotic event (including but not limited to myocardial infarction, unstable angina, stable angina markedly limiting ordinary physical activity, cerebrovascular accident, or ) within 120 days prior to registration
  • Patients must not have a prior history of gastrointestinal (GI) perforation/fistula or other risk factors for perforation within 120 days prior to registration
  • Patients must not have experienced any grade 3-4 GI bleeding within 90 days prior to registration
  • Patient must not have experienced any serious or non-healing wound, ulcer, or bone fracture within 28 days prior to registration
Terms in these criteria, in plain language(20)

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.

Histologically or cytologically confirmed

The diagnosis was confirmed by looking at a sample under a microscope: tissue from a biopsy or surgery (histology), or cells from a fluid or needle sample (cytology).

Your pathology report is the document that shows this.

Metastases

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

Brain metastases

Cancer deposits in the brain from a cancer that started elsewhere in the body (CNS metastases include the spinal cord).

Studies differ: some leave out any brain metastases, some accept ones treated and stable for some weeks. Check what this study allows.

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.

Measurable disease

The amount of disease can be tracked with a defined measurement, so the study can see whether it shrinks or grows. It might be a tumour measured on a scan or, in some blood cancers such as myeloma, a marker measured in blood or urine.

The criteria or the study team say which measurement counts — having no tumour visible on a scan does not by itself rule you out.

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.

CTCAE grade

The US National Cancer Institute’s scale of how severe an adverse event is — any unwanted medical event during a study, such as a symptom, an illness or an abnormal test result, whether or not a treatment caused it. Whether it did is judged separately.

1
Mild.
2
Moderate.
3
Severe.
4
Life-threatening.
5
Death due to the event.

“Side effects of earlier treatment resolved to grade 1 or less” means they have settled to mild or gone.

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.

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.

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.

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.

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.

Reproductive potential

Able to have children. For women this usually means from the first period until menopause, unless permanently unable to through surgery; for men, unless permanently sterile. Read who the line is about — participants, women, men, or their partners.

Criteria about it usually ask for contraception during the study and for a time after it.

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.

Child-Pugh class

A score of how well the liver works in people with liver disease such as cirrhosis: class A is mild, B moderate and C severe.

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.

TIA (transient ischaemic attack)

A “mini-stroke”: temporary stroke-like symptoms caused by reduced blood flow to part of the brain, spinal cord or eye, without signs of a new stroke on a scan.

Stroke symptoms need emergency care at once, even if they go away.

05

Study design

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

Study arms

  • Experimental
    Arm I (ramucirumab, paclitaxel)

    Patients receive ramucirumab IV over 30-60 minutes on days 1 and 15, and paclitaxel IV over 30 minutes on days 1, 8, and 15. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Paclitaxel · Biological: Ramucirumab

  • Experimental
    Arm II (irinotecan, leucovorin, fluorouracil)

    Patients receive irinotecan IV over 90 minutes on days 1 and 15, leucovorin IV over 2 hours on days 1 and 15, and fluorouracil IV bolus on days 1 and 15. Patients also receive fluorouracil IV over 46-48 hours on days 1-3 and 15-17. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

    Drug: Fluorouracil · Drug: Irinotecan · Drug: Irinotecan Hydrochloride · Drug: Leucovorin · Drug: Leucovorin Calcium

Interventions

  • Given IV bolus or IV

    Also known as: 5 Fluorouracil, 5 Fluorouracilum, 5 FU, 5-Fluoro-2,4(1H, 3H)-pyrimidinedione, 5-Fluorouracil, 5-Fluracil, 5-FU, 5FU, AccuSite, Carac, Fluoro Uracil, Fluouracil, Flurablastin, Fluracedyl, Fluracil, Fluril, Fluroblastin, Ribofluor, Ro 2-9757, Ro-2-9757

  • Given IV

  • Given IV

    Also known as: Campto, Camptosar, Camptothecin 11, Camptothecin-11, CPT 11, CPT-11, Irinomedac, Irinotecan Hydrochloride Trihydrate, Irinotecan Monohydrochloride Trihydrate, U-101440E

  • Given IV

    Also known as: Folinic acid

  • Given IV

    Also known as: Adinepar, Calcifolin, Calcium (6S)-Folinate, Calcium Folinate, Calcium Leucovorin, Calfolex, Calinat, Cehafolin, Citofolin, Citrec, Citrovorum Factor, Cromatonbic Folinico, Dalisol, Disintox, Divical, Ecofol, Emovis, Factor, Citrovorum, Flynoken A, Folaren, Folaxin, FOLI-cell, Foliben, Folidan, Folidar, Folinac, Folinate Calcium, folinic acid, Folinic Acid Calcium Salt Pentahydrate, Folinoral, Folinvit, Foliplus, Folix, Imo, Lederfolat, Lederfolin, Leucosar, leucovorin, Rescufolin, Rescuvolin, Tonofolin, Wellcovorin

  • Given IV

    Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat

  • BiologicalRamucirumab

    Given IV

    Also known as: Anti-VEGFR-2 Fully Human Monoclonal Antibody IMC-1121B, Cyramza, IMC-1121B, LY3009806, Monoclonal Antibody HGS-ETR2

06

What researchers measure

Primary outcomes

  1. Progression free survival (PFS)

    PFS will be assessed in all eligible and evaluable (received at least one dose of protocol therapy) patients using the Kaplan-Meier method, with statistical differences in event rates between treatment arms assessed via stratified Cox regression model.

    Time frame: From date of registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 years

Secondary outcomes

  1. Overall survival (OS)

    Probabilities of OS will be estimated using the method of Kaplan-Meier, with statistical differences in event rates between treatment arms assessed via stratified Cox regression model.

    Time frame: From date of registration to date of death due to any cause, assessed up to 3 years

  2. Overall response rate

    Will be assessed by Response Evaluation Criteria in Solid Tumors 1.1. Will be compared across treatment arms via chi-square tests.

    Time frame: Up to 3 years after registration

  3. Incidence of adverse events

    Will be compared across treatment arms via chi-square tests.

    Time frame: Up to 3 years after registration

Other outcomes

  1. CEA level

    CEA levels will be measured at the beginning of the first cycle and every 8 weeks during the study. Maximum decrease in CEA levels from treatment onset and time to maximum decrease in CEA will be summarized in descriptive analyses. Decrease in CEA levels will be defined as high (\>= 50% change) versus low (\< 50% change).

    Time frame: Up to 3 years after registration

07

Study locations

399 of 536 sites recruiting

Showing the first 100 of 536 sites. Choose a country and city above to see the rest.

08

Timeline

1 registry update since Sep 25, 2026
ElapsedEstimatedEstimated, not yet reached

Started Jun 2020 (actual). Primary completion is estimated for Feb 2027, 80 months after the start.

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

Registered
Dec 18, 2019
First posted
Dec 20, 2019
StartActual
Jun 1, 2020
Primary completionEst.
Feb 1, 2027
CompletionEst.
Aug 1, 2027
Last update
Oct 23, 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
Mercy Medical Center is now Withdrawn
Oct 23, 2026
Show all 1 update
  1. Oct 23, 2026
    Mercy Medical Center is now Withdrawn

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 ↗

09

Registry details

Key details

Study ID
NCT04205968
Responsible party
Sponsor
First posted
Dec 20, 2019
Start date
Jun 1, 2020
Primary completion
Feb 1, 2027 (estimated)
Completion
Aug 1, 2027 (estimated)
Last update
Oct 23, 2026

Study contacts

Christy Klepetko
Contact
cklepetko@swog.org
210/614-8808 ext. 9312
Dana Sparks
Contact
dsparks@swog.org
210/614-8808 ext. 1004
Michael J Overman
principal investigator · SWOG Cancer Research Network

Oversight

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

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Studies of the drugs tested here: Fluorouracil · Irinotecan · Leucovorin · Paclitaxel · Ramucirumab

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