NCT04339738

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

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

• Status: Active Not Recruiting
• Phase: Phase 2
• Study type: Interventional
• Enrollment: 89 (actual)
• Sponsor: National Cancer Institute (NCI) · NIH
• Sex: All
• Age: 18 Years
• Healthy volunteers: Not accepted

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.

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

• Skin Angiosarcoma
• Skin Radiation-Related Angiosarcoma
• Visceral Angiosarcoma

Interventions

Type	Name	Description
PROCEDURE	Biospecimen Collection	Undergo collection of blood
DRUG	Cabozantinib S-malate	Given PO
PROCEDURE	Computed Tomography	Undergo CT, spiral CT
PROCEDURE	FDG-Positron Emission Tomography	Undergo FDG-PET
PROCEDURE	Magnetic Resonance Imaging	Undergo MRI
BIOLOGICAL	Nivolumab	Given IV
DRUG	Paclitaxel	Given IV
OTHER	Quality-of-Life Assessment	Ancillary studies
OTHER	Questionnaire Administration	Ancillary studies

Timeline

• Start date: 2020-11-04
• Primary completion: 2025-03-30
• Completion: 2027-01-21
• First posted: 2020-04-09
• Last updated: 2026-02-18

Locations

171 sites across 2 countries: United States, Guam

Regulatory

• FDA-regulated drug study