Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors (RARE CANCER) Trial: RARE 1 Nilotinib and Paclitaxel

Summary

Participation Requirements

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Background: Rare tumors constitute a heterogeneous group of cancers associated with limited treatment options and poor outcomes. Due to their rarity, there are few good models for these diseases to support preclinical evaluation of new anticancer agents. To address these challenges, DCTD s Patient-D...

Background: Rare tumors constitute a heterogeneous group of cancers associated with limited treatment options and poor outcomes. Due to their rarity, there are few good models for these diseases to support preclinical evaluation of new anticancer agents. To address these challenges, DCTD s Patient-Derived Models Repository (PDMR) is generating patient-derived xenograft models of adult and pediatric rare cancers and has screened combinations of approved and investigational anticancer agents in these models. Based on preclinical activity, drug combinations are being tested in patients with rare cancers in a series of connected Phase 2 clinical trials (Rapid Analysis and Response Evaluation of Combination Anti-Neoplastic Agents in Rare Tumors [RARE CANCER]); responses may trigger further evaluation of a treatment in that rare cancer type to further evaluate response rate and mechanism-of-action. Patients who progress will be offered another RARE CANCER trial. The agents used in this trial are the BCR-Abl kinase inhibitor nilotinib and the anti-tubulin agent paclitaxel, which showed greater than additive activity in combination in preclinical xenograft models and subsequently demonstrated clinical efficacy (including partial responses) in patients with solid tumors on the Phase 1 trial 15-C-0086 (NCT02379416). Primary Objectives: - To evaluate the proportion of patients with advanced rare cancers who have objective responses (OR) to treatment with nilotinib and paclitaxel Exploratory Objectives: To evaluate the proportion of patients alive and progression free at 6 months on study agents To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens To examine genomic alterations in circulating tumor DNA (ctDNA) and circulating tumor cells (CTCs) that may be associated with response or resistance To evaluate the pharmacodynamic effects of the combination on biomarkers of cell death and epithelial-to-mesenchymal transition in tumor tissue and CTCs Eligibility: Study participants must have a histologically confirmed solid tumor meeting the RARECARE definition of rare tumor that has progressed on standard therapy known to prolong survival or for which no standard treatment options exist Age >= 18 No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study (6 weeks for nitrosoureas and mitomycin C) or 5 half-lives of the agent, whichever is shorter; toxicity from prior treatment must have recovered to eligibility levels. Adequate organ function; performance status ECOG 0-2 Study Design: Nilotinib will be administered at 300 mg orally BID and paclitaxel will be administered IV at 80 mg/m2 on Days 1, 8, and 15 in 28-day cycles. A single-stage design will be used with a target accrual of 30 eligible patients. If at least 4/30 patients experience an objective response (PR or CR by RECIST 1.1), the combination of nilotinib and paclitaxel will be considered promising. The accrual ceiling is 34 patients.

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