Clinical Trials

The James Cancer Center Columbus, OH

open for enrollment

Crizotinib following Surgery or Radiation Therapy in Treating Patients with High-Risk Uveal Melanoma

Protocol: OSU-14129

Full Title

Phase II Trial of Adjuvant Crizotinib in High-Risk Uveal Melanoma following Definitive Therapy

Purpose

This phase II trial studies how well crizotinib works in treating patients with uveal (eye) melanoma when given after surgery or radiation therapy. Crizotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving crizotinib after surgery or radiation therapy may help prevent the melanoma from returning.

Study Objective

PRIMARY OBJECTIVES:

I. 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.

SECONDARY OBJECTIVES:

I. To determine the overall survival and disease specific survival in this patient population.

II. To evaluate safety and toxicity of adjuvant treatment with crizotinib.

III. To describe the quality of life in patients receiving crizotinib using the Functional Assessment of Cancer Therapy - Melanoma (FACT-M) questionnaire.

TERTIARY OBJECTIVES:

I. To collect patient serum and plasma for circulating tumor deoxyribonucleic acid (DNA) and companion normal gene expression levels.

II. To investigate changes in target genes at baseline in primary tumors and at recurrence in metastatic samples after crizotinib therapy.

III. To establish cell lines or murine xenographs of metastatic recurrences.

OUTLINE:

Patients receive crizotinib orally (PO) twice daily (BID). Courses repeat every 28 days for 48 weeks in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up every 3 months for at least 32 months.

Are you eligible?

Inclusion Criteria:

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 by either surgery or radiotherapy must have been performed within 90 days of initiating protocol therapy

High-risk (class 2) uveal melanoma as determined by gene expression profiling (GEP)

No evidence of metastatic disease

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

Absolute neutrophil count (ANC) > 1,000 cells/mm^3

Platelet count > 75,000/mm^3

Hemoglobin > 9.0 g/dL

Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) < 3 x upper limit of normal (ULN)

Total bilirubin < 2 x ULN

Alkaline phosphatase < 3 x ULN

Serum creatinine < 2 x ULN or creatinine clearance > 60 mL/min

Note: patients with hyperbilirubinemia clinically consistent with an inherited disorder of bilirubin metabolism (e.g., Gilbert syndrome) will be eligible at the discretion of the treating physician and/or the principal investigator

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 until 4 months after completion of crizotinib administration; women of child-bearing potential must have a negative serum pregnancy test within 14 days prior to study entry; 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 therapy, and 4 months after completion of crizotinib administration

Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

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 cytochrome P450, family 3, subfamily A (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 Bazett's formula QTcB >= 480 msec

Concurrent administration of crizotinib and agents that can cause corrected QT (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

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

Melanoma Skin Cancers