Active, not recruitingNCT04339738Updated Sep 8, 2026Results posted

Testing the Addition of Nivolumab to Chemotherapy in Treatment of Soft Tissue Sarcoma

A Phase 2 interventional study of Biospecimen Collection and Cabozantinib S-malate in Skin Angiosarcoma, Skin Radiation-Related Angiosarcoma and Visceral Angiosarcoma, sponsored by National Cancer Institute (NCI). Active, not recruiting at 171 sites in 2 countries. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2026-09-08.

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

Phase: Phase 2
Study type: Interventional
Enrollment: 90
Allocation: Randomized
Ages: 18 Years and older
Sex: All

Study summary

This phase II trial studies how well paclitaxel with and without nivolumab works in treating patients with soft tissue sarcoma that have not received taxane drugs, and how well nivolumab and cabozantinib work in treating taxane pretreated patients with soft tissue sarcoma. Nivolumab works through the body's immune system to help the immune system act against tumor cells. Chemotherapy drugs, such as paclitaxel, 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. Cabozantinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. This trial is being done to see if the combination of nivolumab and paclitaxel or cabozantinib can shrink soft tissue sarcoma and possibly prevent it from coming back.

Read the detailed description

PRIMARY OBJECTIVES:

I. To determine the progression free survival (PFS) for paclitaxel with and without nivolumab in subjects with taxane naive angiosarcoma.

II. To determine the overall response rate (ORR) of nivolumab in combination with cabozantinib S-malate (cabozantinib) in patients with taxane pre-treated angiosarcoma.

SECONDARY OBJECTIVES:

I. To determine the ORR of paclitaxel in combination with nivolumab. II. To determine clinical activity of the addition of nivolumab to paclitaxel or cabozantinib in subjects with angiosarcoma by determination of overall survival (OS) for each combination.

III. To determine clinical activity of the addition of nivolumab to cabozantinib in subjects with taxane pre-treated angiosarcoma by determination of progression free survival (PFS) at 6 months by Response Evaluation Criteria in Solid Tumors (RECIST) version (v)1.1 criteria.

IV. To assess toxicity of the concurrent nivolumab-paclitaxel and nivolumab-cabozantinib combinations in subjects with angiosarcoma based on National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) v.5.0.

V. To measure symptomatic adverse events (AE) for patients via Patient Reported Outcome (PRO)-CTCAE, Functional Assessment of Cancer Therapy General (FACT-G) questionnaire, and Linear Analogue Self-Assessment (LASA).

OUTLINE: Patients who have not previously received a taxane are randomized to Arm I or Arm II. Patients who have previously received a taxane are assigned to Arm III.

ARM I: Patients receive nivolumab intravenously (IV) over 30 minutes on day 1 and paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks for up to 2 years (24 months) for patients who achieve complete response (CR), partial response (PR) or stable disease (SD) on immunotherapy/nivolumab, or in the absence of disease progression or unacceptable toxicity.

ARM II: Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm III.

ARM III (EFFECTIVE OF 10/28/2021, NEW PATIENT ACCRUAL PERMANENTLY CLOSED): Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib orally (PO) daily. Cycles repeat every 4 weeks for up to 2 years (24 months) for patients who achieve CR, PR or SD on immunotherapy/nivolumab, or in the absence of disease progression or unacceptable toxicity.

Patients also undergo collection of blood at baseline and on study, computed tomography (CT) scan, spiral CT, or magnetic resonance imaging (MRI), or FDG-positron emission tomography (FDG-PET) scan throughout the trial.

After completion of study treatment, patients are followed up every 3 months for 3 years.

Conditions studied

Skin Angiosarcoma
Skin Radiation-Related Angiosarcoma
Visceral Angiosarcoma

Browse trials for

Hemangiosarcoma 99

In context

Hemangiosarcoma

99 studies on the registry are indexed under Hemangiosarcoma; 16 are open to participants now.

This study's enrollment of 90 is above the median of 64 across 83 interventional studies indexed under Hemangiosarcoma.

Browse Hemangiosarcoma studies →

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 411 completed or terminated interventional studies of FDA-regulated products, 373 (91%) have results posted.

Browse National Cancer Institute (NCI) studies →

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

Who can participate

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

Eligibility criteria

Inclusion Criteria:

confirmed cutaneous or visceral angiosarcoma, where curative treatment is either not possible or curative modality therapy is declined by the subject. Note: If a subject declines curative modality therapy, the reason must be documented (e.g. excessive morbidity to necessary surgery)
- Note: Radiation induced angiosarcomas are permitted
  - All local diagnostic slides AND 5 x 4-6 micron unstained slides from diagnostic tumor tissue should be available for retrospective central pathology review
Must have per (RECIST) v1.1. Per RECIST v1.1, clinical lesions will only be considered measurable when they are superficial and >= 10 mm diameter as assessed using calipers or ruler (e.g. skin nodules). For the case of skin lesions, documentation by color photography including a ruler to estimate the size of the lesion is required. When lesions can be evaluated by both clinical exam and imagining, imaging evaluation should be undertaken since it is more objective and may also be reviewed at the end of the study. The same method of measurement should be used throughout the study, preferably performed by the same investigator. Areas previously radiated must have demonstrated disease progression at some point over the past 6 months and growth must be subsequent to the last line of anti-cancer directed therapy (e.g. chemotherapy, radiation therapy, surgery)
Not pregnant and not nursing, because this study involves an agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- Therefore, for women of only, a negative pregnancy test done =\< 3 days prior to registration is required
Age >= 18 years
(ECOG) performance status 0-1
Prior Treatment
- Patient must have completed all prior cancer directed therapies (including investigational) >= 7 days prior to cycle 1 day 1
  - Exception: prostate patients who are allowed to concurrently receive androgen suppression therapy
  - Note: Radiation therapy must be completed >= 7 days of day 1 of study treatment, and must not be expected to significantly impact blood count recovery
- There is no limit to overall number of
- No prior inhibitor or PD-L1 inhibitor therapy is permitted
- No prior administration of VEGF TKI therapy is permitted
- Recovery to baseline or' =\< grade 1 version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically non-significant and/or stable on supportive therapy, with the exception of fatigue (which should be =\< grade 2) or alopecia. Note: Patients should be expected to have experienced any nadir and have adequate blood count recovery prior to cycle 1 day 1
Taxane Naive Patients Only: No prior exposure to taxane therapy of any duration for angiosarcoma
Taxane Pre-treated Patients Only (Effective 10/28/2021, new patient accrual to Arm 3 was permanently closed): Prior taxane therapy is allowed at any point prior to registration as long as prior treatment eligibility criteria are met prior to cycle 1 day 1
No major surgery (except the diagnostic ) =\< 28 days of study registration. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Lasik eye surgery are not considered major surgery. Subjects with ongoing complications from prior surgery are not eligible
(ANC) >= 1,500/mm\^3
count >= 100,000/mm\^3
>= 9.0 g/dL
Calculated (Calc.) >= 30 mL/min (per Cockcroft-Gault)
Total =\< 1.5 x (ULN)
- For patients with documented/suspected Gilbert's disease, bilirubin =\< 3 x ULN
(AST)/alanine aminotransferase (ALT) =\< 2.5 x upper limit of normal (ULN)
- For patients with significant hepatic , ALT and AST =\< 5 x ULN. No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment ( class B or C), ascites, coagulopathy or bleeding due to liver dysfunction
Urine protein:creatinine (UPC) ratio \< 1 or urine protein =\< 1+ (Only for Arm 3 Taxane pre-treated and crossover patients)
No uncontrolled central nervous system (CNS) metastases. Patients with history of will be allowed as long as the metastatic sites were adequately treated as demonstrated by clinical and radiographic improvement, and the patient has recovered from the intervention (no residual adverse events > CTCAE grade 1), and the patient has remained without recurrence of new or worsening CNS symptoms for a period of 28 days prior to registration. Treated CNS metastasis (mets) should have no ongoing requirement for , and no evidence of hemorrhage after treatment for at least 28 days prior to registration
No uncontrolled intercurrent illness that would put the patient at undue risk by participation in the study, in the opinion of the investigator
No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, history of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, myocardial ischemia or infarction, severe or unstable angina, (NYHA) class II to IV heart failure, or stroke/ (TIA) within the past 3 months
No thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization. Subjects with a diagnosis of incidental, subsegmental pulmonary embolism (PE) or deep vein thrombosis (DVT) within 6 months are allowed if stable, asymptomatic, and treated with low molecular weight heparin (LMWH) for at least 2 weeks before first dose. Iatrogenic arterial embolization procedures such as tumor arterial embolization or splenic artery embolization are allowed
Patients with a requirement for steroid treatment or other treatment: Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type reaction caused by contact allergen) is permitted
Patients are permitted to enroll if they have vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
Active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as systemic lupus erythematosus (SLE), rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
- Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
(HIV)-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
No planned palliative procedures for alleviation of pain such as radiation therapy or surgery
No untreated or impending spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression
No known or suspected or hypersensitivity to paclitaxel, cabozantinib or nivolumab or to any of the
Disorders associated with a high risk of perforation or fistula formation: active inflammatory bowel disease, active diverticulitis, active cholecystitis, active symptomatic cholangitis or active appendicitis, active acute pancreatitis or active acute obstruction of the pancreatic or biliary duct, or active gastric outlet obstruction; abdominal fistula, gastrointestinal perforation, bowel obstruction, or intra-abdominal abscess within 6 months before randomization. Note: Complete healing of an intra-abdominal abscess must be confirmed before randomization
No clinically significant hematuria, hematemesis, or hemoptysis, or other history of significant bleeding (e.g., pulmonary hemorrhage) within 3 months before randomization
No lesions invading major pulmonary blood vessels
No other clinically significant disorders: uncompensated/symptomatic hypothyroidism; requirements for hemodialysis or peritoneal dialysis; history of solid organ transplantation
Serious non-healing wounds unrelated to cancer are excluded
- Note: Wounds that are cutaneous angiosarcoma are allowed
Chronic concomitant treatment with strong inhibitors and inducers of is not allowed on this study. Patients on strong CYP3A4 inhibitors and inducers must discontinue the drug 7 days and 14 days, respectively prior to registration on the study
Taxane Naive Patients Only: No clinically significant neuropathy (grade >= 2 per NCI CTCAE v5.0)
Taxane Pre-treated only (Effective 10/28/2021, new patient accrual to Arm 3 was permanently closed):
- Stroke (including transient ischemic attack [TIA]), myocardial infarction (MI), or other ischemic event, or thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 6 months before first dose. Subjects with a diagnosis of DVT within 6 months are allowed if stable and treated with LMWH for at least 2 weeks before first dose
- No history of clinically significant coagulopathy
- No uncontrolled hypertension, defined as systolic blood pressure of > 140 mmHg or diastolic pressure > 90 mmHg on anti-hypertensive medications
- No known or suspected gastrointestinal disorder affecting absorption of oral medications (for patients getting cabozantinib)
No clinical, laboratory or radiographic evidence of an active bacterial, fungal, or viral infection requiring treatment at the time of registration. No concurrent use of parenteral (IV) antibiotics is permitted. Oral antibiotics administered for a defined course with expectation of resolution of infection are permitted at the discretion of the investigator
No use of ongoing systemic steroid therapy within 7 days prior to study registration. Dose equivalence of prednisone 10mg daily or less is permitted
Taxane Pre-treated only:
- No current use of aspirin (> 81 mg/day), or any other antiplatelet agents
- Concomitant anticoagulation with oral anticoagulants (e.g., warfarin, direct thrombin inhibitors, and factor Xa inhibitors) or platelet inhibitors (e.g., clopidogrel) is not permitted. Low-dose (prophylactic) low molecular weight heparins (LMWH) are permitted. Anticoagulation with therapeutic doses of LMWH is allowed in subjects with no known brain metastases, no clinically significant hemorrhage, or no complications from a thromboembolic event on the anticoagulation regimen, and who have been on a stable dose of LMWH for at least 2 weeks before first dose
Patients must be able to speak and comprehend English or Spanish in order to complete the mandatory patient-completed measures
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Not pregnant and not nursing, because this study involves an investigational agent whose genotoxic, mutagenic and teratogenic effects on the developing fetus and newborn are unknown
- Therefore, for women of childbearing potential only, a negative pregnancy test done =\< 3 days prior to re-registration is required
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Age >= 18 years
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): ECOG performance status 0-1
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Prior Treatment
- Patient must have completed all prior treatments (including investigational Arm 2 paclitaxel) >= 28 days prior to cycle 1 day 1
  - Exception: prostate patients who are allowed to concurrently receive androgen suppression therapy
  - Note: Re-registration is only permitted after progression on Arm 2
- No prior PD-1 inhibitor or PD-L1 inhibitor therapy is permitted
- Recovery to baseline, or =\< grade 1 CTCAE version 5.0 from toxicity related to any prior treatment, unless adverse events are clinically non-significant and/or stable on supportive therapy, with the exception of fatigue (which should be =\< grade 2) or alopecia. Note: Patients should be expected to have experienced any nadir and have adequate blood count recovery prior to cycle 1 day 1
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No major surgery (except the diagnostic biopsy) =\< 28 days of study re-registration. Procedures such as thoracentesis, paracentesis, percutaneous biopsy, Lasik eye surgery are not considered major surgery. Subjects with clinically relevant ongoing complications from prior surgery are not eligible
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Absolute neutrophil count (ANC) >= 1,500/mm\^3
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Platelet count >= 100,000/mm\^3
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Hemoglobin >= 9.0 g/dL
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Calc. creatinine clearance >= 30 mL/min (per Cockcroft-Gault)
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Total bilirubin =\< 1.5 x upper limit of normal (ULN)
- For patients with documented/suspected Gilbert's disease, bilirubin =\< 3 x ULN
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): AST/ALT =\< 2.5 x upper limit of normal (ULN)
- For patients with significant hepatic metastases, ALT and AST =\< 5 x ULN. No clinically active or chronic liver disease resulting in moderate/severe hepatic impairment (Child-Pugh class B or C), ascites, coagulopathy or bleeding due to liver dysfunction
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): UPC ratio \< 1 or urine protein =\< 1+
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No uncontrolled CNS metastases. Patients with history of CNS metastasis will be allowed as long as the metastatic sites were adequately treated as demonstrated by clinical and radiographic improvement, and the patient has recovered from the intervention (no residual adverse events > CTCAE grade 1), and the patient has remained without recurrence of new or worsening CNS symptoms for a period of 28 days prior to registration. Treated CNS mets should have no ongoing requirement for steroids, and no evidence of hemorrhage after treatment for at least 28 days prior to registration
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No uncontrolled intercurrent illness that would put the patient at undue risk by participation in the study, in the opinion of the investigator
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No history of syncope of cardiovascular etiology, uncontrolled cardiac arrhythmia, History of Mobitz II second degree or third degree heart block without a permanent pacemaker in place, myocardial ischemia or infarction, severe or unstable angina, New York Heart Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (TIA) within the past 3 months
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No thromboembolic event (e.g., deep venous thrombosis, pulmonary embolism) within 1 month before randomization. Subjects with a diagnosis of incidental, subsegmental PE or DVT within 6 months are allowed if stable, asymptomatic, and treated with LMWH for at least 2 weeks before first dose. Iatrogenic arterial embolization procedures such as tumor arterial embolization or splenic artery embolization are allowed
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Patients with a requirement for steroid treatment or other immunosuppressive treatment: Patients should be excluded if they have a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients are permitted to use topical, ocular, intra-articular, intranasal, and inhalational corticosteroids (with minimal systemic absorption). A brief course of corticosteroids for prophylaxis (e.g., contrast dye allergy) or for treatment of non-autoimmune conditions (e.g., delayed-type hypersensitivity reaction caused by contact allergen) is permitted
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): Active autoimmune disease requiring systemic treatment (i.e. disease modifying agents, corticosteroids, or immunosuppressive drugs) within the past 2 years. These include but are not limited to patients with a history of immune-related neurologic disease, multiple sclerosis, autoimmune (demyelinating) neuropathy, Guillain-Barre syndrome, myasthenia gravis; systemic autoimmune disease such as SLE, rheumatoid arthritis, connective tissue diseases, scleroderma, inflammatory bowel disease (IBD), Crohn's, ulcerative colitis, hepatitis; and patients with a history of toxic epidermal necrolysis (TEN), Stevens-Johnson syndrome, or phospholipid syndrome should be excluded because of the risk of recurrence or exacerbation of disease
- Note: Patients are permitted to enroll if they have vitiligo; type I diabetes mellitus; hypothyroidism, pituitary or adrenal insufficiency requiring only hormone replacement; psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger (precipitating event)
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for this trial
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No planned palliative procedures for alleviation of pain such as radiation therapy or surgery
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No untreated or impending spinal cord compression or evidence of spinal metastases with a risk of impending fracture or spinal cord compression
Re-Registration Eligibility Criteria (upon progression on Arm 2 only): No known or suspected contraindications or hypersensitivity to cabozantinib or nivolumab or to any of the exc

Terms in these criteria, in plain language(31)

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.

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.

RECIST

The standard rules for measuring tumours on CT or MRI scans, to tell whether a cancer is shrinking, stable or growing during treatment.

“Measurable disease per RECIST 1.1” usually means at least one tumour 10 mm or more at its longest on a CT scan, or a lymph node 15 mm or more across its short axis.

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.

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.

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.

Line of therapy

A line of therapy is one course of treatment, which may combine several drugs. First-line is the first course given; second-line follows when that stops working or is not tolerated.

“Two prior lines” means two courses that count separately under the study’s rules — not simply two drugs. Ask the study team if you are unsure how yours are counted.

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.

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.

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.

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.

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.

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).

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.

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.

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.

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.

Metastases

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

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.

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.

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.

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.

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.

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.

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.

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.

Excipients

The other ingredients in a medicine besides the active drug, such as fillers, colours or preservatives.

CYP3A (CYP3A4) inhibitors and inducers

CYP3A is a group of enzymes, mainly CYP3A4, in the liver and gut that break down many medicines. Some medicines, supplements and foods (grapefruit, St John’s wort) slow them down or speed them up, which changes how much of a study drug stays in the body.

Studies list them so they can be avoided or switched; bring a list of everything you take, including supplements.

Study design

Phase: Phase 2
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel assignment
Masking: None (open label)
Enrollment: 90 participants (actual)

Study arms

Experimental
Arm I (nivolumab, paclitaxel)
Patients receive nivolumab IV over 30 minutes on day 1 and paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks for up to 2 years (24 months) for patients who achieve CR, PR or SD on immunotherapy/nivolumab, or in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood at baseline and on study, CT scan, spiral CT, or MRI, or FDG-PET scan throughout the trial.
Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: FDG-Positron Emission Tomography · Procedure: Magnetic Resonance Imaging · Biological: Nivolumab · Drug: Paclitaxel · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Experimental
Arm II (paclitaxel)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks for up to 2 years in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood at baseline and on study, CT scan, spiral CT, or MRI, or FDG-PET scan throughout the trial.
Procedure: Biospecimen Collection · Procedure: Computed Tomography · Procedure: FDG-Positron Emission Tomography · Procedure: Magnetic Resonance Imaging · Drug: Paclitaxel · Other: Quality-of-Life Assessment · Other: Questionnaire Administration
Experimental
Arm III (nivolumab, cabozantinib S-malate)
Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib S-malate PO daily. Cycles repeat every 4 weeks for up to 2 years (24 months) for patients who achieve CR, PR or SD on immunotherapy/nivolumab, or in the absence of disease progression or unacceptable toxicity. Patients also undergo collection of blood at baseline and on study, CT scan, spiral CT, or MRI, or FDG-PET scan throughout the trial.
Procedure: Biospecimen Collection · Drug: Cabozantinib S-malate · Procedure: Computed Tomography · Procedure: FDG-Positron Emission Tomography · Procedure: Magnetic Resonance Imaging · Biological: Nivolumab · Other: Quality-of-Life Assessment · Other: Questionnaire Administration

Interventions

ProcedureBiospecimen Collection
Undergo collection of blood
Also known as: Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection
DrugCabozantinib S-malate
Given PO
Also known as: BMS-907351, Cabometyx, Cometriq, XL 184, XL-184, XL184
ProcedureComputed Tomography
Undergo CT, spiral 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
ProcedureFDG-Positron Emission Tomography
Undergo FDG-PET
Also known as: FDG, FDG-PET, FDG-PET Imaging
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
BiologicalNivolumab
Given IV
Also known as: ABP 206, BCD-263, BMS 936558, BMS-936558, BMS936558, CMAB819, MDX 1106, MDX-1106, MDX1106, NIVO, Nivolumab Biosimilar ABP 206, Nivolumab Biosimilar BCD-263, Nivolumab Biosimilar CMAB819, ONO 4538, ONO-4538, ONO4538, Opdivo
DrugPaclitaxel
Given IV
Also known as: Anzatax, Asotax, Bristaxol, Praxel, Taxol, Taxol Konzentrat
OtherQuality-of-Life Assessment
Ancillary studies
Also known as: Quality of Life Assessment
OtherQuestionnaire Administration
Ancillary studies

What researchers measure

Primary outcomes

Progression Free Survival (PFS) in Taxane Naive Patients With Angiosarcoma
Will compare the PFS in taxane naive angiosarcoma patients receiving either (1) paclitaxel + nivolumab compared to (2) paclitaxel alone. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the diameters of target lesions compared to the nadir (smallest) sum of target lesions, any new lesions, or unequivocal progression of existing non-target lesions.
Time frame: 21 months
Overall Response Rate (ORR) in Angiosarcoma Patients Who Have Had Prior Taxane
ORR defined as count of participants that reported a confirmed best response of partial response (PR) or complete response (CR). Evaluation of disease response determination will be defined based on RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Each target lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.
Time frame: 1.5 years

Secondary outcomes

ORR in the Nivolumab + Paclitaxel
Will be estimated by dividing the number of evaluable patients that achieve a confirmed response by the total number of evaluable patients in the nivolumab + paclitaxel combination arm. Additionally a 95% confidence interval will be constructed utilizing properties of the binomial distribution.
Time frame: Up to 3 years
Overall Survival in Each of the 2 Combination Arms
Will be evaluated using the Kaplan-Meier method in order to determine the median survival rate. This median survival rate will be calculated for each of the 2 combination arms (i.e. nivolumab + paclitaxel and nivolumab + cabozantinib).
Time frame: From study enrollment until death due to any cause, assessed up to 3 years
PFS Rate
A patient will be declared an event for this endpoint if they had documented progression (or death) prior to, or at, their 6 month evaluation. This endpoint will be applied to the patients on the nivolumab + cabozantinib combination arm.
Time frame: At 6 months
Incidence of Adverse Events
Maximum grade adverse events will be summarized by treatment arm in a tabular setting. This will be done both with and without regard to the assigned attribution of each adverse event.
Time frame: Up to 3 years
Patient-reported Outcomes (PRO)
Will be assessed via PRO-Common Terminology Criteria for Adverse Events (CTCAE). In order to evaluate this endpoint we will calculate the proportion of patients that report a grade 3+ event along with a 95% confidence interval based on the properties of the binomial distribution. Any other analyses with these data will be done in an exploratory and hypothesis generating manner.
Time frame: Up to 3 years

Results

Posted May 5, 2026

Participant flow

Initial Treatment

Participant flow — Initial Treatment
Milestone	Arm I (Nivolumab, Paclitaxel)	Arm II (Paclitaxel)	Arm III (Nivolumab, Cabozantinib S-malate)
Started	32	35	23
Completed	0	0	3
Not completed	32	35	20
Withdrew: Patient withdrawal prior to beginning treatment	0	2	0
Withdrew: Withdrawn due to ineligibility prior to beginning treatment	1	0	1
Withdrew: Disease progression	16	15	16
Withdrew: Physician decision	2	2	1
Withdrew: Adverse event	1	3	0
Withdrew: Withdrawal by subject	1	3	0
Withdrew: On active treatment	11	5	1
Withdrew: Death	0	2	0
Withdrew: Complicating disease	0	1	0
Withdrew: Patient and physician decision	0	1	0
Withdrew: Clinical progression	0	1	0
Withdrew: Alternative therapy	0	0	1

Crossover Treatment

Participant flow — Crossover Treatment
Milestone	Arm I (Nivolumab, Paclitaxel)	Arm II (Paclitaxel)	Arm III (Nivolumab, Cabozantinib S-malate)
Started	0	9	0
Completed	0	0	0
Not completed	0	9	0
Withdrew: Disease progression	0	4	0
Withdrew: Adverse event	0	2	0
Withdrew: Physician decision	0	1	0
Withdrew: On active treatment	0	2	0

Outcome measures

PrimaryProgression Free Survival (PFS) in Taxane Naive Patients With Angiosarcoma

Will compare the PFS in taxane naive angiosarcoma patients receiving either (1) paclitaxel + nivolumab compared to (2) paclitaxel alone. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.1), as at least a 20% increase in the sum of the diameters of target lesions compared to the nadir (smallest) sum of target lesions, any new lesions, or unequivocal progression of existing non-target lesions.

Time frame:: 21 months
Reported as:: Median · months

Progression Free Survival (PFS) in Taxane Naive Patients With Angiosarcoma
months	Arm I (Nivolumab, Paclitaxel)	Arm II (Paclitaxel)	Arm III (Nivolumab, Cabozantinib S-malate)
Progression Free Survival (PFS) in Taxane Naive Patients With Angiosarcoma	5.6 (4.3 to NA)	8.3 (5.1 to NA)	—

Statistical analysis

Arm I (Nivolumab, Paclitaxel) vs Arm II (Paclitaxel) · Log Rank · p = 0.5782 · Hazard ratio (hr): 1.23 · 95% CI 0.60 to 2.52

PrimaryOverall Response Rate (ORR) in Angiosarcoma Patients Who Have Had Prior Taxane

ORR defined as count of participants that reported a confirmed best response of partial response (PR) or complete response (CR). Evaluation of disease response determination will be defined based on RECIST 1.1. Complete Response (CR): Disappearance of all target lesions. Each target lymph node must have reduction in short axis to \<1.0 cm. Partial Response (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters.

Time frame:: 1.5 years
Reported as:: Count of participants · Participants

Overall Response Rate (ORR) in Angiosarcoma Patients Who Have Had Prior Taxane
Participants	Arm I (Nivolumab, Paclitaxel)	Arm II (Paclitaxel)	Arm III (Nivolumab, Cabozantinib S-malate)
Overall Response Rate (ORR) in Angiosarcoma Patients Who Have Had Prior Taxane	—	—	13

SecondaryORR in the Nivolumab + Paclitaxel

Will be estimated by dividing the number of evaluable patients that achieve a confirmed response by the total number of evaluable patients in the nivolumab + paclitaxel combination arm. Additionally a 95% confidence interval will be constructed utilizing properties of the binomial distribution.

Time frame:: Up to 3 years