Combination Nilotinib and Paclitaxel in Adults With Relapsed Solid Tumors

Summary

Participation Requirements

Description

Background: -The BCR-Abl kinase inhibitor nilotinib demonstrated greater than additive activity in combination with the anti-tubulin agent paclitaxel in preclinical xenograft models, justifying the clinical evaluation of this combination for its antitumor activity Objectives: To establish the safety...

Background: -The BCR-Abl kinase inhibitor nilotinib demonstrated greater than additive activity in combination with the anti-tubulin agent paclitaxel in preclinical xenograft models, justifying the clinical evaluation of this combination for its antitumor activity Objectives: To establish the safety, tolerability, and maximum tolerated dose (MTD) of nilotinib plus paclitaxel in patients with refractory solid tumors, both in adult subjects >=18 years of age and in pediatric/adolescent subjects 12-17 years of age To determine the pharmacokinetics of paclitaxel when administered in combination with nilotinib To evaluate the pharmacodynamic effects of the combination on biomarkers of apoptosis, DNA damage response, and epithelial-to-mesenchymal transition Eligibility: Study participants must have histologically confirmed solid tumor that has progressed on standard therapy known to prolong survival or for which no standard treatment options exist Age greater than or equal to 12 No major surgery, radiation, or chemotherapy within 3 weeks prior to entering the study (6 weeks for nitrosoureas and mitomycin C). Adequate organ function Study Design: This is an open-label Phase I trial During dose escalation, the starting dose of nilotinib will be administered at 300 mg orally BID from cycle 1 day 2 and paclitaxel will be administered IV at 60 mg/m2 at dose level 1 on Days 1, 8, and 15 in 28-day cycles. For cycle 2 on, nilotinib will be administered from day 1. Dose escalation will follow a 3+3 design, with dose limiting toxicities defined during cycle 1. Up to 33 adult patients will be accrued to a PD expansion phase at the MTD to further assess pharmacodynamic endpoints in tumor and CTCs. As of Amendment O (May 2020), patients ages 12-17 will be accrued to a separate pediatric expansion cohort to evaluate the safety, pharmacokinetics, and pharmacodynamics of this combination for pediatric patients.

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