Combination Nilotinib and Paclitaxel in Adults With Relapsed Solid Tumors

Solid Tumors Clinical Trial

Official title: Phase I Trial of the Combination of Nilotinib and Paclitaxel in Adults and Pediatric Patients With Refractory Solid Tumors

Status Recruiting

Clinical Trial Summary

Background: - Researchers want to find better ways to treat cancer. One drug that treats cancer is paclitaxel. Sometimes proteins block that drug from working. Researchers want to see if another drug, nilotinib, helps paclitaxel work better. Objective: - To test the safety of nilotinib plus paclitaxel and find out what doses of the drugs can be given safely to people. Eligibility: - Adults at least 18 years old with advanced cancer that has progressed after receiving standard treatment, or for which no effective therapy exists. Design: - Participants will be screened with tests they usually get in their cancer care: medical history, physical exam, blood and urine tests, heart test, and scans. - Participants will take the two study drugs in 28-day cycles. They will keep a medicine diary. - Nilotinib will be taken by mouth twice every day except day 1 of the first cycle. - Paclitaxel will be given by IV once a week for the first 3 weeks of a cycle. This will usually be done at the clinic. - Most participants will have a weekly study visit every week for cycle 1, then the first 3 weeks of other cycles. They will have: - Physical exam at every visit. - Blood tests multiple times for cycle 1, then the first 3 weeks of other cycles. - Scans every 8 weeks. These may be CT or MRI scans, in a machine that takes pictures. Or they may be ultrasounds, where a wand is pressed on the skin with gel on it. - Around 30 days after stopping the study drugs, participants will be called to discuss any side effects.

Clinical Trial 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, 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 and nilotinib when administered in combination - 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. ;

Related Conditions & MeSH terms

• Neoplasms
• Solid Tumors

• NCT number: NCT02379416
• Study type: Interventional
• Source: National Institutes of Health Clinical Center (CC)
• Contact: DTC Referral Coordinators
• Phone: (240) 781-3499
• Email: dtcreferralcoordinators@nih.gov
• Status: Recruiting
• Phase: Phase 1
• Start date: April 13, 2015
• Completion date: December 27, 2024