Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy

NCT02223819 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: AAAO8010
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 4

Brief Summary

The study is designed to determine the 32 month rate of distant relapse in patients with uveal melanoma who are at high risk of recurrence following definitive therapy with surgery or radiation who receive adjuvant crizotinib; and secondarily, the overall survival and disease specific survival in this patient population.

Conditions

Uveal Melanoma

Keywords

Crizotinib; 14-063

Outcome Measures

Primary Outcomes (1)

• Relapse Free Survival (RFS) Rate at 32 Months

  RFS rate will be defined as the percentage of patients who do not experience any new tumor growth at any site on the body distant from the primary site or death from any cause from the time of study entry to the end of the relevant timepoint. RFS probabilities were estimated using Kaplan-Meier method.

  32 Months

Secondary Outcomes (3)

• Overall Survival (OS)

  Up to 36 months

• Disease-Specific Survival (DSS) Time

  Up to 36 months

• Number of Participants With Treatment Discontinuation Due to Toxicity

  48 weeks

Study Arms (1)

Crizotinib

EXPERIMENTAL

Subjects will receive 48 weeks (12 four-week cycles) of crizotinib 250 mg PO twice a day (BID). Subjects will be evaluated by routine bloodwork and physical exam every 4 weeks while they are receiving crizotinib and during follow up period.

Drug: Crizotinib

Interventions

Crizotinib DRUG

An anti-cancer drug acting as an anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) inhibitor, used to treat non-small cell lung cancer (NSCLC) that has spread to other parts of the body and is caused by a defect in a gene called ALK. Crizotinib will be provided as capsules containing 200 or 250 mg of study medication for oral administration.

Also known as: Xalkori

Crizotinib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Primary diagnosis of uveal melanoma at least 12 mm in largest basal diameter as clinically determined by the treating investigator. Cytologic determination of diagnosis is not required. Size is based on clinical assessment (e.g. by ultrasound or direct ophthalmoscopy) prior to enucleation or radiation therapy.
• Definitive therapy of the primary uveal melanoma must have been performed within 90 days of initiating protocol therapy.
• High-risk (class 2) uveal melanoma as determined by gene expression profiling
• No evidence of metastatic disease.
• Age ≥18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status ≤ 1 (Karnofsky ≥ 70%.
• Life expectancy of greater than 3 months.
• Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels
• Patients must have normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) \>1,000 cells/mm³
• Platelet count \>75,000/mm³
• Hemoglobin \>9.0g/dL
• Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) \<3x upper limited of normal (ULN)
• Total bilirubin \<2x ULN
• Alkaline phosphatase \<3x ULN

You may not qualify if:

• History of another malignancy except for those who have been disease-free for 3 years, or patients with a history of completely resected non-melanoma skin cancer and/or patients with indolent secondary malignancies not requiring active therapy, are eligible. Consult the study Principal Investigator if unsure whether second malignancies meet the requirements specified above.
• Any major surgery or extensive radiotherapy (except that which is required for definitive treatment of primary uveal melanoma), chemotherapy with delayed toxicity, biologic therapy, or immunotherapy within 21 days prior to initiation of study therapy.
• History of prior crizotinib use.
• Use of other investigational drugs within 28 days (or five half-lives, whichever is shorter; with a minimum of 14 days from the last dose) preceding the first dose of study therapy and during the study.
• Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to crizotinib.
• Concurrent administration of crizotinib and a strong inhibitor or inducer of CYP3A is not permitted. Many over-the-counter and dietary supplements also inhibit or induce CYP3A and thus are prohibited.
• A QT interval corrected for heart rate using the Bazett's formula QTcB ≥ 480 msec.
• Concurrent administration of crizotinib and agents that can cause QTc prolongation is not permitted.
• Known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection (with the exception of chronic or cleared HBV and HCV infection, which will be allowed). HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with crizotinib. In addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy.
• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• Columbia University: lead
• Pfizer: collaborator

Study Sites (4)

Mount Sinai Comprehensive Cancer Center

Miami Beach, Florida, 33140, United States

Location

Columbia Univeristy Medical Center

New York, New York, 10032, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

The Ohio State University

Columbus, Ohio, 43210, United States

Location

Related Links

• Memorial Sloan Kettering Cancer Center

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Crizotinib

Condition Hierarchy (Ancestors)

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Uveal Neoplasms; Eye Neoplasms; Neoplasms by Site; Eye Diseases; Uveal Diseases

Intervention Hierarchy (Ancestors)

Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Aminopyridines; Pyridines

Results Point of Contact

• Title: Shaheer A. Khan, DO
• Organization: Columbia University

sk4488@cumc.columbia.edu

212-342-5162

Study Officials

• Shaheer A Khan, DO

  Assistant Professor of Medicine at the Columbia University Medical Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 20, 2014
• First Posted: August 22, 2014
• Study Start: March 1, 2015
• Primary Completion: July 3, 2019
• Study Completion: July 3, 2019
• Last Updated: December 6, 2023
• Results First Posted: December 6, 2023

Record last verified: 2023-12

Locations

US (4)