Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma

NCT00424515 | Completed Phase 2 Results DMC

• 1 other identifier: 06-056
• Study Type: interventional
• Target: 24
• Locations: 1 country
• Sites: 5

Brief Summary

The purpose of this study is to evaluate how effective imatinib (Gleevec) is in treating acral/lentiginous and mucosal melanoma which has spread to other parts of the body in patients who's disease carries a c-kit mutation. Imatinib is a protein-kinase inhibitor. It is believed that imatinib may be effective in blocking signals on certain cancer cells which allow the malignant cells to multiply and spread.

Conditions

Mucosal Melanoma; Acral/Lentiginous Melanoma; Chronically Sun Damaged Melanomas

Keywords

Imatinib; Gleevec

Outcome Measures

Primary Outcomes (1)

• Best Overall Response

  Best overall response (BOR) on treatment was based on RECIST 1.0 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation required within 4 weeks. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. CR is disappearance of all non-target lesions.

  Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m).

Secondary Outcomes (2)

• Time to Progression

  Disease was evaluated radiologically at baseline, after 6-weeks, and at 2-month intervals on treatment and every 3 months long-term. Mean treatment duration was 4 months (range 1-11; amplified/mutated 3m/ 6m).

• Overall Survival

  Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 10.6 months (range 3.7-27.1).

Study Arms (1)

Treatment Arm

EXPERIMENTAL

Imatinib

Drug: Imatinib

Interventions

Imatinib DRUG

Imatinib was given at a dose of 400 mg orally daily (4 100mg pills). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Dosage may have been increased to twice daily if disease worsened and patient was in otherwise good clinical condition.

Also known as: Gleevec

Treatment Arm

Eligibility Criteria

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

You may qualify if:

• Melanomas that arise on chronically sun damaged skin and have pathologic evidence of solar elastosis
• History of primary mucosal or acral/lentiginous melanoma
• Histologically documented stage IV metastatic melanoma
• ECOG performance status 0,1, or 2
• Estimated life expectancy of 6 months or greater
• Age 18 years or older
• Creatinine \< 1.5 x ULN
• ANC \> 1500 ul
• Platelets \> 100,000 ul
• Total bilirubin, AST, and ALT \< 2 x ULN
• Amylase and lipase \< 1.5 x ULN
• C-kit mutation documented from either primary or metastatic tumor site
• \> 4 weeks from prior chemotherapy or investigational drug
• At least one measurable site of disease as defined by at least 1 cm in greatest dimension

You may not qualify if:

• Severe and/or uncontrolled medical disease
• Pregnant or nursing mothers
• Any other significant medical, surgical, or psychiatric condition that my interfere with compliance
• Patient is \< 5 years free of another primary malignancy except: basal cell skin cancer or a cervical carcinoma in situ
• Concurrent treatment with Warfarin
• Prior treatment with c-kit inhibitor
• Patient with Grade III/IV cardiac problems as defined by NYHA criteria
• No H2 blockers or proton pump inhibitors
• Known brain metastasis
• Known chronic liver disease
• Known diagnosis of HIV infection
• Previous radiotherapy to \> 25% of the bone marrow
• Major surgery within 2 weeks prior to study entry
• Patient has received any other investigational agent within 28 days of first study drug dosing
• Chemotherapy within 4 weeks prior to study entry

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Novartis: collaborator

Study Sites (5)

University of Colorado at Denver Health Sciences Center

Denver, Colorado, 80045, United States

Location

H. Lee Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MD Anderson Cancer Center

Houston, Texas, 77030, United States

Location

Related Publications (2)

• Hodi FS, Corless CL, Giobbie-Hurder A, Fletcher JA, Zhu M, Marino-Enriquez A, Friedlander P, Gonzalez R, Weber JS, Gajewski TF, O'Day SJ, Kim KB, Lawrence D, Flaherty KT, Luke JJ, Collichio FA, Ernstoff MS, Heinrich MC, Beadling C, Zukotynski KA, Yap JT, Van den Abbeele AD, Demetri GD, Fisher DE. Imatinib for melanomas harboring mutationally activated or amplified KIT arising on mucosal, acral, and chronically sun-damaged skin. J Clin Oncol. 2013 Sep 10;31(26):3182-90. doi: 10.1200/JCO.2012.47.7836. Epub 2013 Jun 17.

  PMID: 23775962 BACKGROUND

• Zukotynski K, Yap JT, Giobbie-Hurder A, Weber J, Gonzalez R, Gajewski TF, O'Day S, Kim K, Hodi FS, Van den Abbeele AD. Metabolic response by FDG-PET to imatinib correlates with exon 11 KIT mutation and predicts outcome in patients with mucosal melanoma. Cancer Imaging. 2014 Nov 12;14(1):30. doi: 10.1186/s40644-014-0030-0.

  PMID: 25609545 DERIVED

MeSH Terms

Interventions

Imatinib Mesylate

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Piperazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Pyrimidines

Results Point of Contact

• Title: F. Stephen Hodi, MD
• Organization: Dana-Farber Cancer Institute

Stephen_Hodi@dfci.harvard.edu

617.632.5053

Study Officials

• F. Stephen Hodi, MD

  Dana-Farber Cancer Institute

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Melanoma Disease Center Director

Study Record Dates

• First Submitted: January 18, 2007
• First Posted: January 19, 2007
• Study Start: July 1, 2006
• Primary Completion: July 1, 2011
• Study Completion: July 1, 2011
• Last Updated: December 8, 2016
• Results First Posted: December 8, 2016

Record last verified: 2016-06

Data Sharing

• IPD Sharing: Will not share

Locations

US (5)