Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma (BUS255)

• ClinicalTrials.gov Identifier: NCT00424515
• Recruitment Status: Completed
• First Posted: January 19, 2007
• Results First Posted: December 8, 2016
• Last Update Posted: December 8, 2016
• Sponsor: Dana-Farber Cancer Institute
• Collaborator: Novartis
• Information provided by (Responsible Party): F. Stephen Hodi, MD, Dana-Farber Cancer Institute

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Mucosal Melanoma; Acral/Lentiginous Melanoma; Chronically Sun Damaged Melanomas	Drug: Imatinib	Phase 2

Detailed Description:

OBJECTIVES:

Primary

• To determine the response rate of patients with metastatic mucosal, acral/lentiginous, or chronically sun damaged melanomas to treatment with of imatinib.
• To determine the time to progression.

Secondary

• To correlate c-kit mutational status with response to therapy.
• To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
• Tolerability of imatinib.
• To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.
• To correlate c-kit amplification status with response to therapy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 24 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II Study of Imatinib in Patients With Mucosal or Acral/Lentiginous Melanoma and Melanomas That Arise on Chronically Sun Damaged Skin.
• Study Start Date: July 2006
• Actual Primary Completion Date: July 2011
• Actual Study Completion Date: July 2011

Arms and Interventions

Arm	Intervention/treatment
Experimental: Treatment Arm; Imatinib	Drug: Imatinib; 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.; Other Name: Gleevec

Outcome Measures

Primary Outcome Measures :

1. Best Overall Response [ Time Frame: 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). ]
   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.

Secondary Outcome Measures :

1. Time to Progression [ Time Frame: 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). ]
   Time to progression (TTP) based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. 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.
2. Overall Survival [ Time Frame: 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). ]
   Overall survival (OS) is defined as the time from study entry to death or date last known alive.

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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

Contacts and Locations

Locations

United States, Colorado

University of Colorado at Denver Health Sciences Center

Denver, Colorado, United States, 80045

United States, Florida

H. Lee Moffitt Cancer Center

Tampa, Florida, United States, 33612

United States, Illinois

University of Chicago

Chicago, Illinois, United States, 60637

United States, Massachusetts

Dana-Farber Cancer Institute

Boston, Massachusetts, United States, 02115

United States, Texas

MD Anderson Cancer Center

Houston, Texas, United States, 77030

Sponsors and Collaborators

Dana-Farber Cancer Institute

Novartis

Investigators

• Principal Investigator: F. Stephen Hodi, MD; Dana-Farber Cancer Institute

More Information

Publications:

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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;14:30. doi: 10.1186/s40644-014-0030-0.

• Responsible Party: F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT00424515
• Other Study ID Numbers: 06-056
• First Posted: January 19, 2007
• Results First Posted: December 8, 2016
• Last Update Posted: December 8, 2016
• Last Verified: June 2016

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by F. Stephen Hodi, MD, Dana-Farber Cancer Institute:

Imatinib; Gleevec

Additional relevant MeSH terms:

Melanoma; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Imatinib Mesylate; Antineoplastic Agents; Protein Kinase Inhibitors; Enzyme Inhibitors; Molecular Mechanisms of Pharmacological Action