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

This study has been completed.
Sponsor:
Collaborators:
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Novartis
Information provided by (Responsible Party):
F. Stephen Hodi, MD, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier:
NCT00788775
First received: November 10, 2008
Last updated: October 16, 2016
Last verified: August 2016
  Purpose
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.

Condition Intervention Phase
Mucosal Lentiginous Melanoma Acral Melanoma Melanoma Drug: Nilotinib Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase II Study of Nilotinib (AMN107) In TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral or Chronically Sun Damaged Melanoma

Resource links provided by NLM:


Further study details as provided by F. Stephen Hodi, MD, Dana-Farber Cancer Institute:

Primary Outcome Measures:
  • 4-month Progression-Free Survival Rate [ Time Frame: 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. ]
    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.


Secondary Outcome Measures:
  • Progression-Free Survival [ Time Frame: 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). ]
    Progression-free survival (PFS) 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 or death. 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.

  • 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 16.2 months (90%CI 11.7-17.7 months; no/with CNS mets 16.2m/ 11.7m). ]
    Overall survival (OS) is defined as the time from study entry to death or date last known alive.

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


Enrollment: 20
Study Start Date: January 2009
Study Completion Date: March 2014
Primary Completion Date: April 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Nilotinib
Other Names:
  • Tasigna
  • AMN107

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.
  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00788775

Locations
United States, California
The Angeles Clinic and Research Institute
Santa Monica, California, United States, 90404
United States, Colorado
University of Colorado
Aurora, Colorado, United States, 80045
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612
United States, Illinois
University of Chicago
Chicago, Illinois, United States, 60637
United States, Massachusetts
Massachusetts General Hospital
Boston, Massachusetts, United States, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, United States, 02215
United States, New York
Memorial Sloan Kettering Cancer Center
New York, New York, United States, 10065
Sponsors and Collaborators
Dana-Farber Cancer Institute
Brigham and Women's Hospital
Beth Israel Deaconess Medical Center
Massachusetts General Hospital
Novartis
Investigators
Principal Investigator: F. Stephen Hodi, MD Dana-Farber Cancer Institute
  More Information

Publications:
Responsible Party: F. Stephen Hodi, MD, Melanoma Disease Center Director, Dana-Farber Cancer Institute
ClinicalTrials.gov Identifier: NCT00788775     History of Changes
Other Study ID Numbers: 08-244
Study First Received: November 10, 2008
Results First Received: August 22, 2016
Last Updated: October 16, 2016
Individual Participant Data  
Plan to Share IPD: No

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

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

ClinicalTrials.gov processed this record on June 26, 2017