Nilotinib and Paclitaxel in Treating Patients with Refractory Solid Tumors

Status: Approved


This phase I trial studies the side effects and best dose of nilotinib and paclitaxel in treating patients with solid tumors that do not respond to treatment (refractory). Nilotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. Giving nilotinib and paclitaxel together may work better in treating patients with refractory solid tumors because nilotinib may block enzymes that would remove paclitaxel from within the cancer cells where it needs to be for anticancer activity.

Eligibility 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
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 2
  • Life expectancy of greater than 3 months
  • Absolute neutrophil count >= 1,500/mcL
  • Platelets >= 100,000/mcL
  • Total bilirubin =< 1.5 x institutional upper limit of normal (ULN)
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 3 x institutional upper limit of normal; 5.0 x ULN in patients with liver metastases
  • Creatinine =< 1.5 x institutional ULN OR creatinine clearance >= 60 mL/min/1.73 m^2 for patients with creatinine levels > 1.5 mg/dL
  • 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 >= 3 weeks, or biologic therapy or chemotherapy >= 5 half-lives or 3 weeks, whichever is shorter (6 weeks for nitrosoureas and mitomycin C) prior to entering the study; patients must be >= 2 weeks since any prior administration of a study drug in a phase 0 or equivalent study and be >= 1 week from palliative radiation therapy; patients must have recovered to eligibility levels from prior toxicity or adverse events; treatment with bisphosphonates is permitted

Exclusion Criteria

  • Corrected QT interval using Fridericia's formula (QTcF) interval of > 450 msec at study entry; congenital long QT syndrome
  • Sensory/motor neuropathy >= 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 >= 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; 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
  • Human immunodeficiency virus (HIV)-positive patients on combination antiretroviral therapy are ineligible

Locations & Contacts


National Cancer Institute Developmental Therapeutics Clinic
Status: Active
Contact: Shivaani Kummar
Phone: 800-411-1222
National Institutes of Health Clinical Center
Status: Active
Contact: A P Chen
Phone: 301-496-4291

Trial Objectives and Outline


I. To establish the safety, tolerability, and maximum tolerated dose (MTD) of nilotinib plus paclitaxel combination in patients with refractory solid tumors.

II. To determine the pharmacokinetics of paclitaxel and nilotinib when administered in combination.

OUTLINE: This is a dose-escalation study.

Patients receive nilotinib orally (PO) twice daily (BID) on days 1-28 (days 2-28 of course 1 only) and paclitaxel intravenously (IV) over 1 hour on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up for 30 days.

Trial Phase & Type

Trial Phase

Phase I

Trial Type


Lead Organization

Lead Organization
NCI - Center for Cancer Research

Principal Investigator
A P Chen

Trial IDs

Primary ID 15-C-0086
Secondary IDs 9659, NCI-2014-00688 ID NCT02379416