Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu
Trial record 1 of 5 for:    alliance angiosarcoma
Previous Study | Return to List | Next Study

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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04339738
Recruitment Status : Recruiting
First Posted : April 9, 2020
Last Update Posted : February 21, 2021
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)

Brief 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.

Condition or disease Intervention/treatment Phase
Skin Angiosarcoma Skin Radiation-Related Angiosarcoma Visceral Angiosarcoma Drug: Cabozantinib S-malate Biological: Nivolumab Drug: Paclitaxel Other: Quality-of-Life Assessment Other: Questionnaire Administration Phase 2

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.

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) version (v).5.0.

V. To measure symptomatic adverse events (AE) for patients via Patient Reported Outcome (PRO)-CTCAE.

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 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 in the absence of disease progression or unacceptable toxicity. Patients with disease progression may crossover to Arm III.

ARM III: Patients receive nivolumab IV over 30 minutes on day 1 and cabozantinib orally (PO) daily. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.

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

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 90 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : September 4, 2020
Estimated Primary Completion Date : September 30, 2023
Estimated Study Completion Date : September 30, 2023

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
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 in the absence of disease progression or unacceptable toxicity.
Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

Experimental: Arm II (paclitaxel)
Patients receive paclitaxel IV over 1 hour on days 1, 8, and 15. Cycles repeat every 4 weeks in the absence of disease progression or unacceptable toxicity.
Drug: Paclitaxel
Given IV
Other Names:
  • Anzatax
  • Asotax
  • Bristaxol
  • Praxel
  • Taxol
  • Taxol Konzentrat

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies

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 in the absence of disease progression or unacceptable toxicity.
Drug: Cabozantinib S-malate
Given PO
Other Names:
  • BMS-907351
  • Cabometyx
  • Cometriq
  • XL-184
  • XL184

Biological: Nivolumab
Given IV
Other Names:
  • BMS-936558
  • MDX-1106
  • NIVO
  • ONO-4538
  • Opdivo

Other: Quality-of-Life Assessment
Ancillary studies
Other Name: Quality of Life Assessment

Other: Questionnaire Administration
Ancillary studies




Primary Outcome Measures :
  1. Progression free survival (PFS) in taxane naive patients with angiosarcoma [ Time Frame: From registration (randomization) to either progression or death (without progression), assessed up to 3 years ]
    Will compare the PFS in taxane naive angiosarcoma patients receiving either (1) paclitaxel + nivolumab compared to (2) paclitaxel alone.

  2. Overall response rate (ORR) in angiosarcoma patients who have had prior taxane [ Time Frame: Up to 3 years ]
    Will compare the overall response rate (ORR) of nivolumab + cabozantinib in patients with angiosarcoma who have had prior taxanes to historical control of VEGF inhibitors alone.


Secondary Outcome Measures :
  1. ORR in the nivolumab + paclitaxel [ Time Frame: Up to 3 years ]
    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.

  2. Overall survival in each of the 2 combination arms [ Time Frame: From study enrollment until death due to any cause, assessed up to 3 years ]
    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).

  3. PFS rate [ Time Frame: At 6 months ]
  4. Incidence of adverse events [ Time Frame: Up to 3 years ]
    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.

  5. Patient-reported outcomes (PRO) [ Time Frame: Up to 3 years ]
    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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • 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) version (v)1.1. Per RECIST v1.1, clinical lesions will only be considered measurable when they are superficial and P10 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
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-1
  • Prior Treatment

    • Patient must have completed all prior treatments (including investigational) >= 28 days prior to cycle 1 day 1

      • Exception: prostate patients who are allowed to concurrently receive androgen suppression therapy
      • Exception: Targeted small molecule chemotherapy or radiation must be completed >= 14 days of day 1 of study treatment. For targeted chemotherapies, prior therapies must be completed prior to registration and final dose must have occurred > 5 half-lives prior to cycle 1 day 1
    • 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 nonsignificant and/or stable on supportive therapy, with the exception of fatigue (which should be =< grade 2) or alopecia
  • Taxane Naive Patients Only: No prior exposure to taxane therapy of any duration for angiosarcoma
  • Taxane Pre-treated Patients Only: Prior taxane therapy is allowed at any point prior to registration as long as it is >= 28 days 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) >= 1,000/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+
  • 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: serious non-healing wound or ulcer; malabsorption syndrome; uncompensated/symptomatic hypothyroidism; requirements for hemodialysis or peritoneal dialysis; history of solid organ transplantation
  • 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:

    • 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. The subject has prothrombin time (PT)/international normalized ratio (INR) or partial thromboplastin time (PTT) test =< 1.3 x the laboratory ULN within 7 days before the first dose of study treatment
    • 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): 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 nonsignificant and/or stable on supportive therapy, with the exception of fatigue (which should be =< grade 2) or alopecia
  • 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) >= 1,000/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 p

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04339738


Locations
Show Show 79 study locations
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Layout table for investigator information
Principal Investigator: Juneko E Grilley-Olson Alliance for Clinical Trials in Oncology
Layout table for additonal information
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT04339738    
Other Study ID Numbers: NCI-2020-02153
NCI-2020-02153 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
A091902 ( Other Identifier: Alliance for Clinical Trials in Oncology )
A091902 ( Other Identifier: CTEP )
U10CA180821 ( U.S. NIH Grant/Contract )
First Posted: April 9, 2020    Key Record Dates
Last Update Posted: February 21, 2021
Last Verified: September 2020
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Yes
Plan Description: 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.
URL: https://grants.nih.gov/policy/sharing.htm

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Additional relevant MeSH terms:
Layout table for MeSH terms
Hemangiosarcoma
Sarcoma
Neoplasms, Connective and Soft Tissue
Neoplasms by Histologic Type
Neoplasms
Neoplasms, Vascular Tissue
Paclitaxel
Nivolumab
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Immunological