A Multicenter Phase II Trial of Paclitaxel with and without Nivolumab in Taxane Naïve, and Nivolumab and Cabozantinib in Taxane Pre-treated 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.
2.1 Co-primary Objectives
2.1.1 To determine the progression free survival (PFS) for paclitaxel with and without nivolumab in subjects with taxane naïve angiosarcoma.
2.1.2 To determine the overall response rate (ORR) of nivolumab in combination with cabozantinib in patients with taxane pre-treated angiosarcoma.
2.2 Secondary objectives
2.2.1 To determine the ORR of paclitaxel in combination with nivolumab.
2.2.2 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.
2.2.3 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 RECIST v1.1 criteria.
2.2.4 To assess toxicity of the concurrent nivolumab-paclitaxel and nivolumab-cabozantinib combinations in subjects with angiosarcoma based on NCI-CTCAE v.5.0.
2.2.5 To measure symptomatic adverse events (AE) for patients via PRO-CTCAE.
Histologically confirmed cutaneous or visceral angiosarcoma, where curative treatment is either not possible or curative modality therapy is declined by the subject
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)
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
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
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) => Adequate organ function per protocol
No uncontrolled central nervous system (CNS) metastases
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
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
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
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
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