Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy

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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 Phase

Phase 2

Study Type

Interventional


Primary Outcome

Relapse Free Survival (RFS) rate

Secondary Outcome

 Overall Survival (OS) rate

Condition

Uveal Melanoma

Intervention

Crizotinib

Study Arms / Comparison Groups

 Crizotinib
Description:  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.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

34

Start Date

March 2015

Completion Date

August 2022

Primary Completion Date

August 2022

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.
      

Gender

All

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Richard Carvajal, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT02223819

Organization ID

AAAO8010


Responsible Party

Principal Investigator

Study Sponsor

Columbia University

Collaborators

 Pfizer

Study Sponsor

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


Verification Date

March 2021