Bethesda, Maryland 20892


Purpose:

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.


Study summary:

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 - 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 18 - 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 - 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 25 patients will be accrued to a PD expansion phase at the MTD to further assess pharmacodynamic endpoints in tumor and CTCs.


Criteria:

- INCLUSION CRITERIA: - Patients must have histologically confirmed solid tumors that have progressed on standard therapy known to prolong survival or for which no standard treatment options exist. - Age greater than or equal to 18 years. - ECOG performance status less than or equal to 2. - Life expectancy of greater than 3 months - Patients must have normal organ and marrow function as defined below: - Absolute neutrophil count greater than or equal to 1,500/mcL - Platelets greater than or equal to 100,000/mcL - Total bilirubin less than or equal to 1.5 X institutional ULN - AST(SGOT)/ALT(SGPT) less than or equal to 3 X institutional upper limit of normal; 5.0 x ULN in patients with liver metastases - creatinine less than or equal to 1.5 X institutional ULN OR - creatinine clearance greater than or equal to 60 mL/min/1.73 m2 for patients with creatinine levels greater than 1.5 mg/dL - Nilotinib and paclitaxel have both been assigned to pregnancy category D by the FDA. For this reason, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation and for at least 3 months after dosing with study drugs ceases. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately. Men treated or enrolled on this protocol must also agree to use adequate contraception prior to the study, for the duration of study participation, and 3 months after completion of study drug administration. - Patients must have completed radiation therapy, or major surgery greater than or equal to 3 weeks, or biologic therapy or chemotherapy greater than or equal to 5 half-lives or 3 weeks, whichever is shorter (6 weeks for nitrosoureas and mitomycin C) prior to entering the study. Patients must be greater than or equal to 2 weeks since any prior administration of a study drug in a Phase 0 or equivalent study and be greater than or equal to1 week from palliative radiation therapy. Patients must have recovered to eligibility levels from prior toxicity or adverse events. Treatment with bisphosphonates is permitted. - For the PD-expansion cohort, patients must be willing to give biopsies for research and have tumors amenable for the acceptable biopsy procedures. EXCLUSION CRITERIA: - QTcF interval of less than 450 msec at study entry; congenital long QT syndrome - Sensory/motor neuropathy less than or equal to Grade 2 - Patients who are receiving any other investigational agents. - Patients with active brain metastases or carcinomatous meningitis are excluded from this clinical trial. Patients with treated brain metastases, whose brain metastatic disease has remained stable for less than or equal to 4 weeks without requiring steroid and anti-seizure medication are eligible to participate. - History of allergic reactions attributed to compounds of similar chemical or biologic composition to study drugs. - Uncontrolled intercurrent illness including, but not limited to, serious untreated infection, symptomatic respiratory failure/congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements. - Pregnant women are excluded from this study because nilotinib and paclitaxel have been assigned to pregnancy category D by the FDA. Because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with the study drugs, breastfeeding should be discontinued prior to the first dose of study drug and women should refrain from nursing throughout the treatment period and for 3 months following the last dose of study drug. - HIV-positive patients on combination antiretroviral therapy are ineligible because of possible PK interactions with study drugs. - Both men and women of all races and ethnic groups are eligible for this trial.


NCT ID:

NCT02379416


Primary Contact:

Principal Investigator
Alice P Chen, M.D.
National Cancer Institute (NCI)

Rasa Vilimas, R.N.
Phone: (301) 594-4949
Email: rasa.vilimas@nih.gov


Backup Contact:

Email: chenali@mail.nih.gov
Alice P Chen, M.D.
Phone: (240) 781-3320


Location Contact:

Bethesda, Maryland 20892
United States

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office
Phone: 888-624-1937

Site Status: Recruiting


Data Source: ClinicalTrials.gov

Date Processed: November 19, 2017

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