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Combination Nilotinib and Paclitaxel in Adults With Relapsed Solid Tumors

This study is currently recruiting participants. (see Contacts and Locations)
Verified February 1, 2017 by National Institutes of Health Clinical Center (CC)
Sponsor:
Information provided by (Responsible Party):
National Institutes of Health Clinical Center (CC) ( National Cancer Institute (NCI) )
ClinicalTrials.gov Identifier:
NCT02379416
First received: March 4, 2015
Last updated: May 12, 2017
Last verified: February 1, 2017
  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.

Condition Intervention Phase
Solid Tumors
Drug: Nilotinib + Paclitaxel
Phase 1

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: No masking
Primary Purpose: Treatment
Official Title: Phase I Trial of the Combination of Nilotinib and Paclitaxel in Adults With Refractory Solid Tumors

Resource links provided by NLM:


Further study details as provided by National Institutes of Health Clinical Center (CC):

Primary Outcome Measures:
  • To establish the safety, tolerability, and maximum tolerated dose (MTD) of nilotinib plus paclitaxel combination in patients with refractory solid tumors [ Time Frame: Cycle 1 ]

Secondary Outcome Measures:
  • To determine the pharmacokinetics of paclitaxel when administered in combination with nilotinib [ Time Frame: Cycle 1 ]

Estimated Enrollment: 40
Study Start Date: February 20, 2015
Estimated Study Completion Date: December 23, 2017
Estimated Primary Completion Date: December 23, 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
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.
Drug: Nilotinib + Paclitaxel
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

Detailed 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
  • 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.
  Eligibility

Ages Eligible for Study:   18 Years to 120 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02379416

Contacts
Contact: Rasa Vilimas, R.N. (301) 594-4949 rasa.vilimas@nih.gov
Contact: Alice P Chen, M.D. (301) 496-4291 chenali@mail.nih.gov

Locations
United States, Maryland
National Institutes of Health Clinical Center, 9000 Rockville Pike Recruiting
Bethesda, Maryland, United States, 20892
Contact: For more information at the NIH Clinical Center contact National Cancer Institute Referral Office    888-624-1937      
Sponsors and Collaborators
National Cancer Institute (NCI)
Investigators
Principal Investigator: Alice P Chen, M.D. National Cancer Institute (NCI)
  More Information

Additional Information:
Publications:
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT02379416     History of Changes
Other Study ID Numbers: 150086
15-C-0086
Study First Received: March 4, 2015
Last Updated: May 12, 2017

Keywords provided by National Institutes of Health Clinical Center (CC):
Drug Efflux
Taxanes
Combination
Bcr-Abl Kinase Inhibitors
Neoplasms

Additional relevant MeSH terms:
Paclitaxel
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on May 22, 2017