Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma

NCT ID: NCT00788775

Last Updated: 2018-11-15

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-01-23
• Study Completion Date: 2014-03-31

Brief Summary

Given the poor prognosis and limited treatment options available for patients with mucosal or acral/lentiginous melanomas who develop metastatic disease, genetic discoveries of KIT mutations in these cancers present the need to test multi-targeted kinase inhibitors with potent KIT inhibitory activity in this patient population. Imatinib and other tyrosine kinase inhibitors (TKIs) have the potential to be effective in this patient population, but patients may develop resistance to treatment. Therefore, in this study, we propose to test nilotinib in patients with metastatic mucosal, acral, or chronically sun-damaged melanoma following treatment with another TKI.

Detailed Description

OBJECTIVES:

Primary

• To estimate the proportion of patients, with metastatic mucosal, acral, or chronically sun damaged melanomas, whose tumors have KIT aberrations, and who progressed or could not tolerate a KIT targeting tyrosine kinase inhibitor (TKI) (e.g. including but not limited to imatinib mesylate, sunitinib, or dasatanib), who are alive and without progression of disease four months after beginning treatment with nilotinib.

Secondary

• To determine early evidence of biologic and clinical activity by best overall response rate.
• To estimate time to progression of disease and overall survival.
• To determine the tolerability of nilotinib.
• To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
• To correlate c-kit mutational status and amplification status with response to therapy.
• To evaluate the feasibility of nilotinib.
• To evaluate the tolerability of nilotinib in patients with brain metastases.

Conditions

Mucosal Lentiginous Melanoma; Acral Melanoma; Melanoma

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Nilotinib

Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit.

Group Type: EXPERIMENTAL

Nilotinib

Intervention Type: DRUG

Interventions

Nilotinib

Intervention Type: DRUG

Other Intervention Names

Tasigna; AMN107

Eligibility Criteria

Inclusion Criteria

• 18 years of age or older
• Histologically documented diagnosis of mucosal melanoma or acral melanoma or chronically sun damaged melanoma as evidenced by solar elastosis on pathology
• Patient's tumor with evidence for KIT mutation or amplification. Patient tumors that already have documented mutations or amplification do not have to have tissue submitted again for analysis to confirm eligibility
• Have failed, progressed, or not been able to tolerate other tyrosine kinase inhibitors including but not limited to imatinib mesylate, sunitinib or dasatinib treatment.
• At least one measurable site of disease
• ECOG Performance Status 0, 1 or 2
• Adequate organ function as outlined in the protocol
• Negative pregnancy test for female patients of childbearing potential

Exclusion Criteria

• Patient has received any other investigational agents within 28 days of first day of study drug dosing unless the disease is rapidly progressing
• Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ
• Female patients who are pregnant or breast-feeding
• Patient has a severe and/or uncontrolled medical disease
• Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption
• Patient with electrolyte abnormality unless the level can be corrected to normal levels prior to initiating study drug
• Known brain metastasis
• Known chronic liver disease
• Patient has received chemotherapy within 4 weeks prior to study entry, unless the disease is rapidly progressing (6 weeks for nitrosourea or mitomycin-C)
• Patient previously received radiotherapy to 25% or greater of the bone marrow
• Patient had a major surgery within 2 weeks prior to study entry
• Impaired cardiac function
• QTc > 450msec on screening ECG
• Myocardial infarction within one year prior to starting nilotinib
• Other clinically significant heart disease
• Patients who are currently receiving treatment with any of the medications that have the potential to prolong QT interval
• Patients who are currently receiving Warfarin > 1mg/day
• Patient with any significant history of non-compliance to medical regimens or with the inability to grant reliable informed consent
• Prior therapy with nilotinib

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Brigham and Women's Hospital

OTHER

Sponsor Role: collaborator

Beth Israel Deaconess Medical Center

OTHER

Sponsor Role: collaborator

Massachusetts General Hospital

OTHER

Sponsor Role: collaborator

Novartis

INDUSTRY

Sponsor Role: collaborator

Dana-Farber Cancer Institute

OTHER

Sponsor Role: lead

Responsible Party

F. Stephen Hodi, MD

Melanoma Disease Center Director

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

F. Stephen Hodi, MD

Role: PRINCIPAL_INVESTIGATOR

Dana-Farber Cancer Institute

Locations

The Angeles Clinic and Research Institute

Santa Monica, California, United States

University of Colorado

Aurora, Colorado, United States

Moffitt Cancer Center

Tampa, Florida, United States

University of Chicago

Chicago, Illinois, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

Dana-Farber Cancer Institute

Boston, Massachusetts, United States

Beth Israel Deaconess Medical Center

Boston, Massachusetts, United States

Memorial Sloan Kettering Cancer Center

New York, New York, United States

Countries

United States

References

Carvajal RD, Lawrence DP, Weber JS, Gajewski TF, Gonzalez R, Lutzky J, O'Day SJ, Hamid O, Wolchok JD, Chapman PB, Sullivan RJ, Teitcher JB, Ramaiya N, Giobbie-Hurder A, Antonescu CR, Heinrich MC, Bastian BC, Corless CL, Fletcher JA, Hodi FS. Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition. Clin Cancer Res. 2015 May 15;21(10):2289-96. doi: 10.1158/1078-0432.CCR-14-1630. Epub 2015 Feb 18.

Reference Type: RESULT

PMID: 25695690 (View on PubMed)

Other Identifiers

08-244

Identifier Type: -

Identifier Source: org_study_id