Lenalidomide, Sunitinib, and Cyclophosphamide in Treating Patients With Stage IV Eye Melanoma

NCT00482911 | Terminated Phase 2 Results FDA Drug

• 2 other identifiers: 070134NCI-07-C-0134
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 1

Brief Summary

RATIONALE: Lenalidomide may stop the growth of tumor cells by blocking blood flow to the tumor. Sunitinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as cyclophosphamide, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving lenalidomide together with sunitinib and low doses of cyclophosphamide once a day may kill more tumor cells. PURPOSE: This phase II trial is studying how well giving lenalidomide together with sunitinib and cyclophosphamide works in treating patients with stage IV eye melanoma.

Conditions

Intraocular Melanoma; Malignant Conjunctival Neoplasm

Keywords

recurrent intraocular melanoma; metastatic intraocular melanoma; ciliary body and choroid melanoma, medium/large size; extraocular extension melanoma; iris melanoma; conjunctival melanoma

Outcome Measures

Primary Outcomes (3)

• Response Rate (Complete and Partial Response)

  Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response is the disappearance of all target lesions. Partial response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions taking as reference the baseline sum LD.

  2 years

• Toxicity

  Here is the number of participants with adverse events. For a detailed list of adverse events see the adverse event module.

  16 months

• Overall Survival

  Time from date of on study to the date of death from any cause or last follow up

  up to 16 months

Secondary Outcomes (2)

• Progression Free Survival

  up to 16 months

• Changes in Gene Expression, Methylation and Protein Modification

  Baseline and end of treatment course 1 and 2, approximately 42 days

Study Arms (2)

Cohort 1-lenalidomide & cyclophosphamide

EXPERIMENTAL

Participants first started on 2 Interventions (Dose A-QD) in Cycle 1, with 10 mg Lenalidomide (Len) once daily and 50 mg Cyclophosphamide (Cyc) once daily; 25 mg Sunitinib (Sun) was added once daily as a 3rd Intervention (Dose B-QD) from Cycle 2 onwards. Doses were adjusted in subsequent cycles depending on toxicity, including incremental step downs to 5/25/12.5 mg Len/Cyc/Sun once daily (Dose C-QD) or once every other day (Dose C-QOD).

Drug: cyclophosphamide; Drug: lenalidomide

Cohort 2-sunitinib & cyclophosphamide

EXPERIMENTAL

2 participants started Cycle 1 with Dose B as described above and had adjusted-dosing as described for Cohort 1. The remaining 7 participants began Cycle 1 with 10 mg Len, 25 mg Cyc and 12.5 mg Sun once daily (Dose D-QD). Doses were adjusted in subsequent cycles depending on toxicity, including step up to 10/50/12.5 mg Len/Cyc/Sun once daily (Dose E-QD) and step down to Dose D once every other day (Dose D-QOD).

Drug: cyclophosphamide; Drug: sunitinib malate

Interventions

cyclophosphamide DRUG

25-50 mg by mouth once daily on days 1-28.

Also known as: cytoxan

Cohort 1-lenalidomide & cyclophosphamide; Cohort 2-sunitinib & cyclophosphamide

lenalidomide DRUG

10 mg by mouth once daily on days 1-28.

Also known as: revlimid

Cohort 1-lenalidomide & cyclophosphamide

sunitinib malate DRUG

12.5 - 25 mg by mouth once daily on days 1-28.

Also known as: sutent

Cohort 2-sunitinib & cyclophosphamide

Eligibility Criteria

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

DISEASE CHARACTERISTICS: * Histologically confirmed ocular melanoma * Stage IV disease * Measurable disease * No active brain metastases * Patients with brain metastases must have had a complete excision or radiotherapy and remain asymptomatic with stable disease by magnetic resonance imaging (MRI) or computed tomography (CT) scan for ≥ 6 months PATIENT CHARACTERISTICS: * Eastern Cooperative Oncology Group (ECOG) performance status 0-2 * Life expectancy \> 3 months * Granulocyte count \> 1,500/mm\^3 * Platelet count \> 100,000/mm\^3 * Creatinine ≤ 1.5 mg/dL OR creatinine clearance \> 60 mL/min * Bilirubin ≤ 2.0 mg/dL * Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) \< 10 times upper limit of normal (ULN) * Prothrombin time (PT)/partial thromboplastin time (PTT)/International Normalized Ratio (INR) normal * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use one highly effective method of contraception (with an additional method) or barrier methods of contraception for ≥ 4 weeks before, during, and for ≥ 4 weeks after completion of study therapy * Ejection fraction normal by echocardiogram * No acute, critical illness, including serious untreated infection * No history of any of the following: * Unstable or newly diagnosed angina pectoris * Myocardial infarction within the past 6 months * New York Heart Association class II-IV heart disease * Congestive heart failure * Chronic obstructive lung disease requiring oxygen therapy * Chronic uncontrollable hypertension * Uncontrolled seizure activity * No known human immunodeficiency virus (HIV) positivity * No known hypersensitivity reaction to thalidomide, lenalidomide, sunitinib malate, or cyclophosphamide PRIOR CONCURRENT THERAPY: * See Disease Characteristics * Recovered from all prior therapy * At least 4 weeks since prior surgery, chemotherapy (6 weeks for mitomycin C, nitrosoureas, or carboplatin), hormonal therapy, radiotherapy, or biological therapy * No concurrent grapefruit or grapefruit juice * No other concurrent antitumor therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• National Institutes of Health Clinical Center (CC): lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

Warren Grant Magnuson Clinical Center - NCI Clinical Trials Referral Office

Bethesda, Maryland, 20892-1182, United States

Location

MeSH Terms

Conditions

Uveal Melanoma

Interventions

Cyclophosphamide; Lenalidomide; Sunitinib

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)

Phosphoramide Mustards; Nitrogen Mustard Compounds; Mustard Compounds; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals; Phosphoramides; Organophosphorus Compounds; Phthalimides; Phthalic Acids; Acids, Carbocyclic; Carboxylic Acids; Piperidones; Piperidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Isoindoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Pyrroles; Azoles; Indoles

Results Point of Contact

• Title: Steven A. Rosenberg, M.D.
• Organization: National Cancer Institute, National Institutes of Health

sbpso@mail.nih.gov

301-435-7507

Study Officials

• Steven K. Libutti, MD

  NCI - Surgery Branch

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Deputy Clinical Director, Center for Cancer Research

Study Record Dates

• First Submitted: June 4, 2007
• First Posted: June 5, 2007
• Study Start: April 1, 2007
• Primary Completion: April 1, 2009
• Study Completion: April 1, 2009
• Last Updated: March 27, 2017
• Results First Posted: November 14, 2012

Record last verified: 2017-02

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)