Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy

• ClinicalTrials.gov Identifier: NCT02223819
• Recruitment Status: Active, not recruiting
• First Posted: August 22, 2014
• Last Update Posted: December 18, 2019
• Sponsor: Columbia University
• Collaborator: Pfizer
• Information provided by (Responsible Party): Richard D. Carvajal, Columbia University

Tracking Information

• First Submitted Date: August 20, 2014
• First Posted Date: August 22, 2014
• Last Update Posted Date: December 18, 2019
• Actual Study Start Date: March 2015
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: May 10, 2016)

Relapse Free Survival (RFS) rate [ Time Frame: Up to 36 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.

Original Primary Outcome Measures (submitted: August 20, 2014)

Relapse free survival (RFS) [ Time Frame: 3 years ]

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.

Current Secondary Outcome Measures (submitted: May 10, 2016)

• Overall Survival (OS) rate [ Time Frame: Up to 36 months ]
  OS will be defined as the time from treatment start to date of death or last followup and estimated using Kaplan-Meier methodology.
• Disease-Specific Survival (DSS) time [ Time Frame: Up to 36 months ]
  DSS is defined as the time from treatment start to death due to disease or last followup.
• Prevalence of treatment discontinuation due to toxicity [ Time Frame: 48 weeks ]
  Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.

Original Secondary Outcome Measures (submitted: August 20, 2014)

• Overall survival (OS) [ Time Frame: 3 years ]
  Overall survival (OS) will be defined as the time from treatment start to date of death or last followup and estimated using Kaplan-Meier methodology.
• Disease-specific survival (DSS) [ Time Frame: 3 years ]
  Disease-specific survival (DSS) is defined as the time from treatment start to death due to disease or last followup.
• Toxicity [ Time Frame: 3 years ]
  Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
• Official Title: Phase II Trial of Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
• 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.

Detailed Description

Uveal melanoma is the most common primary intraocular malignancy in adults, and arises from melanocytes within the choroid plexus of the eye. Melanomas of the ocular and adnexal structures comprise approximately 5% of all melanomas and are biologically and prognostically distinct from cutaneous melanoma. In the United States, an estimated 2000 patients are diagnosed with this disease each year.

The development of metastasis in this disease is common and occurs in approximately 50% of patients with posterior uveal melanoma within 15 years after the initial diagnosis and treatment. Uveal melanoma is thought to be particularly resistant to systemic treatment, and no systemic therapy has yet been demonstrated to improve survival. Drugs commonly used to treat advanced cutaneous melanoma rarely achieve durable responses in patients with uveal melanoma.

• Study Type: Interventional
• Study Phase: Phase 2
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Uveal Melanoma

Intervention

Drug: Crizotinib

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.

Other Name: Xalkori

Study Arms

Experimental: Crizotinib

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.

Intervention: Drug: Crizotinib

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Active, not recruiting
• Actual Enrollment (submitted: June 29, 2018): 34
• Original Estimated Enrollment (submitted: August 20, 2014): 30
• Estimated Study Completion Date: August 2022
• Estimated Primary Completion Date: August 2022 (Final data collection date for primary outcome measure)

Eligibility Criteria

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 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
• Serum creatinine <2x ULN or a creatinine clearance > 60mL/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 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.

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT02223819
• Other Study ID Numbers: AAAO8010
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No

IPD Sharing Statement

• Plan to Share IPD: Undecided

• Responsible Party: Richard D. Carvajal, Columbia University
• Study Sponsor: Columbia University
• Collaborators: Pfizer

Investigators

• Principal Investigator: Richard Carvajal, MD; Associate Professor of Medicine at the Columbia University Medical Center

• PRS Account: Columbia University
• Verification Date: December 2019