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

NCT00788775 | Completed Phase 2 Results DMC

• 1 other identifier: 08-244
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 8

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.

Conditions

Mucosal Lentiginous Melanoma; Acral Melanoma; Melanoma

Keywords

nilotinib

Outcome Measures

Primary Outcomes (1)

• 4-month Progression-Free Survival Rate

  4-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. 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.

  Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 4 months.

Secondary Outcomes (3)

• Progression-Free Survival

  Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).

• Overall Survival

  Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 16.2 months (90%CI 11.7-17.7 months; no/with CNS mets 16.2m/ 11.7m).

• Best Overall Response

  Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).

Study Arms (1)

Nilotinib

EXPERIMENTAL

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.

Drug: Nilotinib

Interventions

Nilotinib DRUG

Also known as: Tasigna, AMN107

Nilotinib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Dana-Farber Cancer Institute: lead
• Brigham and Women's Hospital: collaborator
• Beth Israel Deaconess Medical Center: collaborator
• Massachusetts General Hospital: collaborator
• Novartis: collaborator

Study Sites (8)

The Angeles Clinic and Research Institute

Santa Monica, California, 90404, United States

Location

University of Colorado

Aurora, Colorado, 80045, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

University of Chicago

Chicago, Illinois, 60637, United States

Location

Massachusetts General Hospital

Boston, Massachusetts, 02114, United States

Location

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

Beth Israel Deaconess Medical Center

Boston, Massachusetts, 02215, United States

Location

Memorial Sloan Kettering Cancer Center

New York, New York, 10065, United States

Location

Related Publications (1)

• 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.

  PMID: 25695690 RESULT

MeSH Terms

Conditions

Melanoma

Interventions

nilotinib

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases

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: November 10, 2008
• First Posted: November 11, 2008
• Study Start: January 23, 2009
• Primary Completion: April 1, 2011
• Study Completion: March 1, 2014
• Last Updated: November 15, 2018
• Results First Posted: December 8, 2016

Record last verified: 2018-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (8)