Brief Title
Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma
Official Title
A Phase II Study of Nilotinib (AMN107) In TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral or Chronically Sun Damaged Melanoma
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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
4-month Progression-Free Survival Rate
Secondary Outcome
Progression-Free Survival
Condition
Mucosal Lentiginous Melanoma
Intervention
Nilotinib
Study Arms / Comparison Groups
Nilotinib
Description: 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.
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
20
Start Date
January 23, 2009
Completion Date
March 2014
Primary Completion Date
April 2011
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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
F. Stephen Hodi, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00788775
Organization ID
08-244
Responsible Party
Principal Investigator
Study Sponsor
Dana-Farber Cancer Institute
Collaborators
Brigham and Women's Hospital
Study Sponsor
F. Stephen Hodi, MD, Principal Investigator, Dana-Farber Cancer Institute
Verification Date
October 2018