This phase II ComboMATCH treatment trial evaluates nilotinib with paclitaxel for the treatment of patients with solid cancers that are growing, spreading, or getting worse (progressive) and that have previously been treated with taxane therapies. Nilotinib is in a class of medications called kinase inhibitors. It works by binding to and blocking the action of a protein called ABL, which signals tumor cells to multiply. This helps slow or stop the proliferation of tumor cells. Paclitaxel is a drug that blocks cell growth by stopping cell division and it may kill tumor cells. Giving nilotinib with paclitaxel may be effective at treating patients with progressive solid cancers that have previously been treated with taxane therapies.
PRIMARY OBJECTIVE: I. To evaluate the proportion of patients with taxane-refractory advanced malignancies who have objective responses (OR) to treatment with nilotinib hydrochloride monohydrate (nilotinib) and paclitaxel. SECONDARY OBJECTIVE: I. Collect tissue and provide it to the ComboMATCH registration protocol to assess concordance between the diagnostic tumor mutation profile generated by the designated laboratories, the pre-treatment biopsy mutation profile, and the pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) mutation profile from plasma, as described in ComboMATCH registration protocol. For this treatment substudy, the outcome objective will be to report the proportion of cases providing sufficient tissue for that integrated scientific activity in the ComboMATCH registration protocol. EXPLORATORY OBJECTIVES: I. To evaluate progression free survival (PFS) at 6 months on study agents. II. To identify genomic and transcriptomic determinants of response and resistance in tumor biopsy specimens and cell-free deoxyribonucleic acid (DNA). OUTLINE: Patients receive nilotinib hydrochloride monohydrate orally (PO) twice daily (BID) on days 1-28 and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15 of each cycle. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) or magnetic resonance imaging (MRI) throughout the study. Patients also undergo collection of blood samples and tumor biopsy on study. After completion of study treatment, patients are followed until disease progression, and for survival for 3 years from registration.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
40
Undergo biopsy
Undergo collection of blood samples
Undergo CT
Undergo MRI
Given PO
Given IV
University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Kingman Regional Medical Center
Kingman, Arizona, United States
Stanford Cancer Institute Palo Alto
Palo Alto, California, United States
Presbyterian Intercommunity Hospital
Whittier, California, United States
UCHealth University of Colorado Hospital
Aurora, Colorado, United States
Best objective response
Evaluated using Response Evaluation Criteria in Solid Tumors version 1.1. 90% two-sided confidence intervals will be used for reporting estimated rates.
Time frame: Up to 3 years
Progression free survival
Distribution will be estimated using the method of Kaplan and Meier.
Time frame: From registration to documented disease progression or death from any cause, assessed up to 3 years
Overall survival
Distribution will be estimated using the method of Kaplan and Meier.
Time frame: From registration to death from any cause, assessed up to 3 years
Incidence of adverse events
Will be determined using the National Cancer Institute's Common Terminology Criteria for Adverse Events. Exact binomial confidence intervals will be used for adverse event rates.
Time frame: Up to 3 years
Concordance of diagnostic tumor mutation profile, pre-treatment tumor biopsy mutation profile, and pre-treatment circulating tumor deoxyribonucleic acid (ctDNA) profile
Whole-exome sequencing, ribonucleic acid sequencing, and ctDNA sequencing will be performed on mandatory tissue biopsies and/or blood specimens.
Time frame: Up to 3 years
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