AzTrials
AzTrials

Skin AngiosarcomaPhase 2NCT04339738

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

A Phase 2 study testing Biospecimen Collection, Cabozantinib S-malate and Computed Tomography in people with Skin Angiosarcoma and Skin Radiation-Related Angiosarcoma, run by National Cancer Institute (NCI) at 171 sites in 2 countries.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Biospecimen Collection, Cabozantinib S-malate and Computed Tomography
Could I receive a placebo?
No, everyone receives an active treatment
How many people
90 participants
Where
171 sitesin 2 countries
Study dates
4 Nov 2020to 21 Jan 2027
Phase
Phase 2

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Histologically 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 measurable disease per Response Evaluation Criteria in Solid Tumors (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 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 registration is required
Show all 90Show fewer
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (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 prior lines of therapy
  • No prior PD-1 inhibitor or PD-L1 inhibitor therapy is permitted
  • No prior administration of VEGF TKI 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
  • 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 biopsy) =< 28 days of study 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
  • Absolute neutrophil count (ANC) >= 1,500/mm^3
  • Platelet count >= 100,000/mm^3
  • Hemoglobin >= 9.0 g/dL
  • Calculated (Calc.) creatinine clearance >= 30 mL/min (per Cockcroft-Gault)
  • Total bilirubin =< 1.5 x upper limit of normal (ULN)
  • For patients with documented/suspected Gilbert's disease, bilirubin =< 3 x ULN
  • Aspartate aminotransferase (AST)/alanine aminotransferase (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
  • 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 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 metastasis (mets) should have no ongoing requirement for steroids, 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, New York Heart Association (NYHA) class II to IV heart failure, or stroke/transient ischemic attack (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 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
  • 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)
  • Human immunodeficiency virus (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 contraindications or hypersensitivity to paclitaxel, cabozantinib or nivolumab or to any of the excipients
  • 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 CYP3A4 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

Who cannot join

None listed.

Trial locations and contacts

171 sites in 2 countries.

171 sites in 2 countries

United States170 sites

  • Hawaii Cancer Care - Westridge

    ‘Aiea, Hawaii, 96701

  • Pali Momi Medical Center

    ‘Aiea, Hawaii, 96701

  • Queen's Cancer Center - Pearlridge

    ‘Aiea, Hawaii, 96701

  • The Cancer Center of Hawaii-Pali Momi

    ‘Aiea, Hawaii, 96701

  • The Queen's Medical Center - West Oahu

    ‘Ewa Beach, Hawaii, 96706

  • OSF Saint Anthony's Health Center

    Alton, Illinois, 62002

  • Mary Greeley Medical Center

    Ames, Iowa, 50010

  • McFarland Clinic - Ames

    Ames, Iowa, 50010

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • Emory University Hospital Midtown

    Atlanta, Georgia, 30308

  • UCHealth University of Colorado Hospital

    Aurora, Colorado, 80045

  • Rush-Copley Medical Center

    Aurora, Illinois, 60504

  • Mercy Oncology and Hematology - Clayton-Clarkson

    Ballwin, Missouri, 63011

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • Central Care Cancer Center - Bolivar

    Bolivar, Missouri, 65613

  • McFarland Clinic - Boone

    Boone, Iowa, 50036

  • Massachusetts General Hospital Cancer Center

    Boston, Massachusetts, 02114

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • Roswell Park Cancer Institute

    Buffalo, New York, 14263

  • Fairview Ridges Hospital

    Burnsville, Minnesota, 55337

  • Minnesota Oncology - Burnsville

    Burnsville, Minnesota, 55337

  • Cambridge Medical Center

    Cambridge, Minnesota, 55008

  • UNC Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Carolinas Medical Center/Levine Cancer Institute

    Charlotte, North Carolina, 28203

  • Atrium Health Pineville/LCI-Pineville

    Charlotte, North Carolina, 28210

  • Northwestern University

    Chicago, Illinois, 60611

  • Rush MD Anderson Cancer Center

    Chicago, Illinois, 60612

  • University of Chicago Comprehensive Cancer Center

    Chicago, Illinois, 60637

  • Siteman Cancer Center at Saint Peters Hospital

    City of Saint Peters, Missouri, 63376

  • Ohio State University Comprehensive Cancer Center

    Columbus, Ohio, 43210

  • Mercy Hospital

    Coon Rapids, Minnesota, 55433

  • Siteman Cancer Center at West County Hospital

    Creve Coeur, Missouri, 63141

  • Carle at The Riverfront

    Danville, Illinois, 61832

  • Northwestern Medicine Cancer Center Kishwaukee

    DeKalb, Illinois, 60115

  • Smilow Cancer Hospital-Derby Care Center

    Derby, Connecticut, 06418

  • City of Hope Comprehensive Cancer Center

    Duarte, California, 91010

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Marshfield Medical Center-EC Cancer Center

    Eau Claire, Wisconsin, 54701

  • Fairview Southdale Hospital

    Edina, Minnesota, 55435

  • Carle Physician Group-Effingham

    Effingham, Illinois, 62401

  • NorthShore University HealthSystem-Evanston Hospital

    Evanston, Illinois, 60201

  • Smilow Cancer Hospital Care Center-Fairfield

    Fairfield, Connecticut, 06824

  • McFarland Clinic - Trinity Cancer Center

    Fort Dodge, Iowa, 50501

  • Mercy Hospital Fort Smith

    Fort Smith, Arkansas, 72903

  • Parkview Regional Medical Center

    Fort Wayne, Indiana, 46845

  • Vanderbilt-Ingram Cancer Center Cool Springs

    Franklin, Tennessee, 37067

  • Unity Hospital

    Fridley, Minnesota, 55432

  • Gibbs Cancer Center-Gaffney

    Gaffney, South Carolina, 29341

  • UF Health Cancer Institute - Gainesville

    Gainesville, Florida, 32610

  • Central Care Cancer Center - Garden City

    Garden City, Kansas, 67846

  • Northwestern Medicine Cancer Center Delnor

    Geneva, Illinois, 60134

  • Smilow Cancer Hospital Care Center at Glastonbury

    Glastonbury, Connecticut, 06033

  • NorthShore University HealthSystem-Glenbrook Hospital

    Glenview, Illinois, 60026

  • Central Care Cancer Center - Great Bend

    Great Bend, Kansas, 67530

  • Smilow Cancer Hospital Care Center at Greenwich

    Greenwich, Connecticut, 06830

  • Gibbs Cancer Center-Pelham

    Greer, South Carolina, 29651

  • Smilow Cancer Hospital Care Center - Guilford

    Guilford, Connecticut, 06437

  • Hackensack University Medical Center

    Hackensack, New Jersey, 07601

  • Smilow Cancer Hospital Care Center at Saint Francis

    Hartford, Connecticut, 06105

  • NorthShore University HealthSystem-Highland Park Hospital

    Highland Park, Illinois, 60035

  • Hawaii Cancer Care Inc - Waterfront Plaza

    Honolulu, Hawaii, 96813

  • Island Urology

    Honolulu, Hawaii, 96813

  • Queen's Cancer Cenrer - POB I

    Honolulu, Hawaii, 96813

  • Queen's Medical Center

    Honolulu, Hawaii, 96813

  • Straub Clinic and Hospital

    Honolulu, Hawaii, 96813

  • University of Hawaii Cancer Center

    Honolulu, Hawaii, 96813

  • Hawaii Cancer Care Inc-Liliha

    Honolulu, Hawaii, 96817

  • Hawaii Diagnostic Radiology Services LLC

    Honolulu, Hawaii, 96817

  • Kuakini Medical Center

    Honolulu, Hawaii, 96817

  • Queen's Cancer Center - Kuakini

    Honolulu, Hawaii, 96817

  • The Cancer Center of Hawaii-Liliha

    Honolulu, Hawaii, 96817

  • Kapiolani Medical Center for Women and Children

    Honolulu, Hawaii, 96826

  • Mayo Clinic in Florida

    Jacksonville, Florida, 32224-9980

  • McFarland Clinic - Jefferson

    Jefferson, Iowa, 50129

  • Freeman Health System

    Joplin, Missouri, 64804

  • Mercy Hospital Joplin

    Joplin, Missouri, 64804

  • Straub Medical Center - Kahului Clinic

    Kahului, Hawaii, 96732

  • Castle Medical Center

    Kailua, Hawaii, 96734

  • Northwestern Medicine Lake Forest Hospital

    Lake Forest, Illinois, 60045

  • Northwell Health/Center for Advanced Medicine

    Lake Success, New York, 11042

  • Cancer Centers of Southwest Oklahoma Research

    Lawton, Oklahoma, 73505

  • Wilcox Memorial Hospital and Kauai Medical Clinic

    Lihue, Hawaii, 96766

  • Fairview Clinics and Surgery Center Maple Grove

    Maple Grove, Minnesota, 55369

  • Minnesota Oncology Hematology PA-Maplewood

    Maplewood, Minnesota, 55109

  • Saint John's Hospital - Healtheast

    Maplewood, Minnesota, 55109

  • McFarland Clinic - Marshalltown

    Marshalltown, Iowa, 50158

  • Marshfield Medical Center-Marshfield

    Marshfield, Wisconsin, 54449

  • Carle Physician Group-Mattoon/Charleston

    Mattoon, Illinois, 61938

  • Medical College of Wisconsin

    Milwaukee, Wisconsin, 53226

  • Abbott-Northwestern Hospital

    Minneapolis, Minnesota, 55407

  • Hennepin County Medical Center

    Minneapolis, Minnesota, 55415

  • Health Partners Inc

    Minneapolis, Minnesota, 55454

  • Marshfield Medical Center - Minocqua

    Minocqua, Wisconsin, 54548

  • UPMC Hillman Cancer Center - Monroeville

    Monroeville, Pennsylvania, 15146

  • Monticello Cancer Center

    Monticello, Minnesota, 55362

  • SSM Health Good Samaritan

    Mount Vernon, Illinois, 62864

  • Vanderbilt Breast Center at One Hundred Oaks

    Nashville, Tennessee, 37204

  • Vanderbilt University/Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Yale University

    New Haven, Connecticut, 06520

  • Cancer Center of Western Wisconsin

    New Richmond, Wisconsin, 54017

  • New Ulm Medical Center

    New Ulm, Minnesota, 56073

  • NYP/Columbia University Medical Center/Herbert Irving Comprehensive Cancer Center

    New York, New York, 10032

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

  • Yale-New Haven Hospital North Haven Medical Center

    North Haven, Connecticut, 06473

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • Mercy Hospital Oklahoma City

    Oklahoma City, Oklahoma, 73120

  • Nebraska Methodist Hospital

    Omaha, Nebraska, 68114

  • Smilow Cancer Hospital-Orange Care Center

    Orange, Connecticut, 06477

  • Thomas Jefferson University Hospital

    Philadelphia, Pennsylvania, 19107

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

  • Mayo Clinic Hospital in Arizona

    Phoenix, Arizona, 85054

  • UPMC-Saint Margaret

    Pittsburgh, Pennsylvania, 15215

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • Oregon Health and Science University

    Portland, Oregon, 97239

  • Fairview Northland Medical Center

    Princeton, Minnesota, 55371

  • Marshfield Medical Center-Rice Lake

    Rice Lake, Wisconsin, 54868

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • North Memorial Medical Health Center

    Robbinsdale, Minnesota, 55422

  • Mayo Clinic in Rochester

    Rochester, Minnesota, 55905

  • Mercy Clinic-Rolla-Cancer and Hematology

    Rolla, Missouri, 65401

  • Phelps Health Delbert Day Cancer Institute

    Rolla, Missouri, 65401

  • Heartland Regional Medical Center

    Saint Joseph, Missouri, 64506

  • Park Nicollet Clinic - Saint Louis Park

    Saint Louis Park, Minnesota, 55416

  • Regions Hospital

    Saint Paul, Minnesota, 55101

  • United Hospital

    Saint Paul, Minnesota, 55102

  • University of Utah Sugarhouse Health Center

    Salt Lake City, Utah, 84106

  • Huntsman Cancer Institute/University of Utah

    Salt Lake City, Utah, 84112

  • Mayo Clinic in Arizona

    Scottsdale, Arizona, 85259

  • Fred Hutchinson Cancer Center

    Seattle, Washington, 98109

  • University of Washington Medical Center - Montlake

    Seattle, Washington, 98195

  • Saint Francis Regional Medical Center

    Shakopee, Minnesota, 55379

  • LSU Health Sciences Center at Shreveport

    Shreveport, Louisiana, 71103

  • North Grove Medical Park

    Spartanburg, South Carolina, 29303

  • Spartanburg Medical Center

    Spartanburg, South Carolina, 29303

  • Spartanburg Medical Center - Mary Black Campus

    Spartanburg, South Carolina, 29307

  • Mercy Hospital Springfield

    Springfield, Missouri, 65804

  • CoxHealth South Hospital

    Springfield, Missouri, 65807

  • Mercy Infusion Center - Chippewa

    St Louis, Missouri, 63109

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • Mercy Hospital South

    St Louis, Missouri, 63128

  • Siteman Cancer Center-South County

    St Louis, Missouri, 63129

  • Siteman Cancer Center at Christian Hospital

    St Louis, Missouri, 63136

  • Mercy Hospital Saint Louis

    St Louis, Missouri, 63141

  • Marshfield Medical Center-River Region at Stevens Point

    Stevens Point, Wisconsin, 54482

  • Lakeview Hospital

    Stillwater, Minnesota, 55082

  • Moffitt Cancer Center-International Plaza

    Tampa, Florida, 33607

  • Moffitt Cancer Center - McKinley Campus

    Tampa, Florida, 33612

  • Moffitt Cancer Center

    Tampa, Florida, 33612

  • Smilow Cancer Hospital-Torrington Care Center

    Torrington, Connecticut, 06790

  • Smilow Cancer Hospital Care Center-Trumbull

    Trumbull, Connecticut, 06611

  • University of Arizona Cancer Center-Orange Grove Campus

    Tucson, Arizona, 85704

  • Banner University Medical Center - Tucson

    Tucson, Arizona, 85719

  • University of Arizona Cancer Center-North Campus

    Tucson, Arizona, 85719

  • SMC Center for Hematology Oncology Union

    Union, South Carolina, 29379

  • Carle Cancer Center

    Urbana, Illinois, 61801

  • The Carle Foundation Hospital

    Urbana, Illinois, 61801

  • Ridgeview Medical Center

    Waconia, Minnesota, 55387

  • Northwestern Medicine Cancer Center Warrenville

    Warrenville, Illinois, 60555

  • Mercy Hospital Washington

    Washington, Missouri, 63090

  • Sibley Memorial Hospital

    Washington D.C., District of Columbia, 20016

  • Smilow Cancer Hospital-Waterbury Care Center

    Waterbury, Connecticut, 06708

  • Smilow Cancer Hospital Care Center - Waterford

    Waterford, Connecticut, 06385

  • Smilow Cancer Hospital Care Center - Westerly

    Westerly, Rhode Island, 02891

  • Marshfield Medical Center - Weston

    Weston, Wisconsin, 54476

  • UPMC Susquehanna

    Williamsport, Pennsylvania, 17701

  • Divine Providence Hospital

    Williamsport, Pennsylvania, 17754

  • Rice Memorial Hospital

    Willmar, Minnesota, 56201

  • Minnesota Oncology Hematology PA-Woodbury

    Woodbury, Minnesota, 55125

  • Fairview Lakes Medical Center

    Wyoming, Minnesota, 55092

  • Rush-Copley Healthcare Center

    Yorkville, Illinois, 60560

Other trials in United States

Guam1 site

  • FHP Health Center-Guam

    Tamuning, 96913

Other trials in Guam

About this study

Official title: A Multicenter Phase II Trial of Paclitaxel With and Without Nivolumab in Taxane Naive, and Nivolumab and Cabozantinib in Taxane Pretreated Subjects With Angiosarcoma

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:

  1. 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:

  1. 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.

  1. 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.

Being tested
Biospecimen Collection, Cabozantinib S-malate, Computed Tomography, FDG-Positron Emission Tomography, Magnetic Resonance Imaging

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood

  • Cabozantinib S-malateDrug

    Also called BMS-907351, Cabometyx, Cometriq, XL 184

    Given PO

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo CT, spiral CT

  • FDG-Positron Emission TomographyProcedure or surgery

    Also called FDG, FDG-PET, FDG-PET Imaging

    Undergo FDG-PET

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • NivolumabBiological

    Also called ABP 206, BCD-263, BMS 936558, BMS-936558

    Given IV

  • PaclitaxelDrug

    Also called Anzatax, Asotax, Bristaxol, Praxel

    Given IV

  • Quality-of-Life AssessmentOther

    Also called Quality of Life Assessment

    Ancillary studies

  • Questionnaire AdministrationOther

    Ancillary studies

Study groups in NCT04339738
Study groupRoleWhat they receive
Arm I (nivolumab, paclitaxel)ExperimentalPatients 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.
Receives: 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
Arm II (paclitaxel)ExperimentalPatients 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.
Receives: 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
Arm III (nivolumab, cabozantinib S-malate)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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.

    Measured: 21 months

  2. 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.

    Measured: 1.5 years

Secondary outcomes (5)

  1. 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.

    Measured: Up to 3 years

  2. 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).

    Measured: From study enrollment until death due to any cause, assessed up to 3 years

  3. 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.

    Measured: At 6 months

  4. 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.

    Measured: Up to 3 years

  5. 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.

    Measured: Up to 3 years

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted9 Apr 2020
  2. Study start4 Nov 2020
  3. Primary completion30 Mar 2025
  4. Study completion21 Jan 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
90 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT04339738
Sponsor's protocol ID
NCI-2020-02153
Other IDs
NCI-2020-02153, A091902, A091902, U10CA180821
Status last verified
Jul 2026
First submitted
8 Apr 2020
Last updated
8 Sep 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
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.

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