Nivolumab (Opdivo®) Plus ABI-009 (Nab-rapamycin) for Advanced Sarcoma and Certain Cancers
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|ClinicalTrials.gov Identifier: NCT03190174|
Recruitment Status : Completed
First Posted : June 16, 2017
Last Update Posted : December 6, 2021
|Condition or disease||Intervention/treatment||Phase|
|Ewing Sarcoma PEComa Epithelioid Sarcoma Desmoid Tumor Chordoma Non Small Cell Lung Cancer Urothelial Carcinoma Melanoma Renal Cell Carcinoma Squamous Cell Carcinoma Hepatocellular Carcinoma Classical Hodgkin Lymphoma Colorectal Cancer MTOR Activating Mutation||Drug: Nab-Rapamycin Biological: Nivolumab||Phase 1 Phase 2|
The primary objective of this study is to investigate the maximum tolerated dose of ABI-009, an mTOR inhibitor, when given sequentially with nivolumab in advanced Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urethelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors
The secondary objectives are to investigate the disease control rate (DCR) and progression free survival (PFS) using nivolumab/ABI-009 combination therapy in advanced Ewing's sarcoma, PEComa, epithelioid sarcoma, desmoid tumor, chordoma, non-small cell lung cancer, small cell lung cancer, urethelial carcinoma, melanoma, renal cell carcinoma, squamous cell carcinoma of head and neck, hepatocellular carcinoma, classical Hodgkin's lymphoma, MSI-H/dMMR metastatic colorectal cancer, and tumors with genetic mutations sensitive to mTOR inhibitors
The exploratory objectives are (1) To correlate progression free survival (PFS) based on Immune-related Response Criteria (irRECIST) with that based on RECIST v1.1, and (2) To correlate PFS with PD-1 and PD-L1 expression in patients' tumors.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||34 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1/2 Study Using Nivolumab and ABI-009 for Advanced Sarcoma, Advanced Carcinoma Treated With PD1 Inhibitors, and Tumors With Genetic Mutations Sensitive to mTOR Inhibitors|
|Actual Study Start Date :||August 24, 2017|
|Actual Primary Completion Date :||December 1, 2021|
|Actual Study Completion Date :||December 2, 2021|
Experimental: Arm 1
This is an open label, dose-seeking phase 1b study using a defined dose of nivolumab and escalating doses of Nab-Rapamycin (ABI-009) given intravenously.
I. Dose Escalation Phase 1 Part of Study: The study will employ the standard "cohort of three" design. No intra-patient dose escalation will take place.
II. Expansion Phase 1b Part of Study: Following dose escalation, an additional 22-28 patients will receive ABI-009 at the MTD and defined doses of nivolumab to assess overall safety and potential efficacy in a greater number of patients. Patients in the expansion phase of the study may continue treatment up to 18 three-week cycles or until significant disease progression or unacceptable toxicity occurs.
Escalating doses of ABI-009 will be given IV over 30 min for 2 of every 3 weeks beginning Day 8 Cycle 2. Only nivolumab will be given in Cycle 1. At Dose Level 1, 3-6 patients will receive 56 mg/m2; at Dose Level 2, 3-6 six patients will receive 75 mg/m2; and at Dose Level 3, 3-6 patients will receive 100 mg/m2.
Other Name: ABI-009
A defined dose of nivolumab, 3 mg/kg, will be given IV over 30 minutes q 3 weeks
Other Name: Opdivo
- Maximum tolerated dose [ Time Frame: 6 months ]Dose escalation study, determination of maximum tolerated dose (MTD) in previously treated patients with soft tissue sarcoma
- Disease control rate [ Time Frame: 24 months ]Effect of dual therapy with ABI-009 and nivolumab on Disease Control Rate in advanced soft tissue sarcoma
- Progression free survival [ Time Frame: 24 months ]Effect of dual therapy with ABI-009 and nivolumab on progression free survival (PFS)
- Overall survival [ Time Frame: 24 months ]Effect of dual therapy with ABI-009 and nivolumab on overall survival in advanced soft tissue sarcoma
- Disease control rate and PD-L1 expression in tumors [ Time Frame: 30 months ]Correlation between disease control rate and PD-L1 expression in patients' tumors
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): NCT03190174
|United States, California|
|Sarcoma Oncology Research Center|
|Santa Monica, California, United States, 90403|
|Principal Investigator:||Erlinda M Gordon, MD||Sarcoma Oncology Research Center|