Uveal MelanomaPhase 2NCT02223819
Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
A Phase 2 study testing Crizotinib in people with Uveal Melanoma, run by Columbia University at 4 sites in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Uveal Melanoma
- What is being tested?
- Crizotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 4 sitesUnited States
- Study dates
- Mar 2015to 3 Jul 2019
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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%.
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- 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.
Who cannot join
- 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.
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- 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.
Trial locations and contacts
4 sites in 1 country.
United States4 sites
The Ohio State University
Columbus, Ohio, 43210
Mount Sinai Comprehensive Cancer Center
Miami Beach, Florida, 33140
Columbia Univeristy Medical Center
New York, New York, 10032
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
About this study
Official title: Phase II Trial of Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
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.
Read the 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.
- Conditions
- Uveal Melanoma
- Being tested
- Crizotinib
- Keywords
- Crizotinib, 14-063
- Medical subject headings
- Uveal Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CrizotinibDrug
Also called Xalkori
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Crizotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 32 Months
Secondary outcomes (3)
Overall Survival (OS)
OS will be defined as the time from treatment start to date of death or last followup. Participants were followed up to 36 months after treatment start and Kaplan-Meier survival analysis was used to generate the Overall Survival estimate.
Measured: Up to 36 months
Disease-Specific Survival (DSS) Time
DSS is defined as the time from treatment start to death due to disease or last followup. Participants who die from other causes will be censored.
Measured: Up to 36 months
Number of Participants With Treatment Discontinuation Due to Toxicity
Toxicity grading will be performed in accordance with NCI CTCAE, version 4.0.
Measured: 48 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Aug 2014 (estimated)
- Study startMar 2015
- Primary completion3 Jul 2019
- Study completion3 Jul 2019
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Uveal MelanomaStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Pfizer
- Responsible party
- Sponsor
- Investigators
- Shaheer A Khan, DO, Principal investigator, Assistant Professor of Medicine at the Columbia University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02223819
- Sponsor's protocol ID
- AAAO8010
- Status last verified
- Dec 2023
- First submitted
- 20 Aug 2014
- Last updated
- 6 Dec 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 6 Dec 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Adjuvant Crizotinib in High-Risk Uveal Melanoma Following Definitive Therapy
- ClinicalTrials.gov ID
- NCT02223819
- Acronym / sponsor ID
- AAAO8010
- Conditions
- Uveal Melanoma
- Keywords
- Crizotinib, 14-063
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Pfizer
- Study start
- Mar 2015 (actual)
- Primary completion
- 3 Jul 2019 (actual)
- Study completion
- 3 Jul 2019 (actual)
- First posted
- 22 Aug 2014 (estimated)
- Results
- Posted 6 Dec 2023
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Crizotinib | Experimental | Drug: CrizotinibSubjects 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- 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.
Key exclusion criteria (10 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| CrizotinibAlso: XalkoriAn 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. | Drug | Crizotinib |
Primary outcome
Relapse Free Survival (RFS) Rate at 32 Months
Time frame: 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.
3 secondary outcomes
Overall Survival (OS)
Time frame: Up to 36 months
Disease-Specific Survival (DSS) Time
Time frame: Up to 36 months
Number of Participants With Treatment Discontinuation Due to Toxicity
Time frame: 48 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Dec 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Memorial Sloan Kettering Cancer CenterLink provided by the sponsor.
- Individual participant dataSharing planned: Undecided
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A Phase 1 and 2 Study of VMD-102 in Hepatocellular Carcinoma and Other Solid Tumors
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HS-IT101 Injection Versus Chemotherapy in the Treatment of Advanced Melanoma（FASTIL-Mela02）
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Shaheer A Khan, DO principal investigator
Assistant Professor of Medicine at the Columbia University Medical Center
4 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Crizotinib in people with Uveal Melanoma, run by Columbia University at 4 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 19 inclusion and 10 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 6 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 4 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Dec 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Relapse Free Survival (RFS) Rate at 32 Months (time frame: 32 Months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 6 Dec 2023.