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

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



      * 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.


        -  To determine early evidence of biologic and clinical activity by best overall response

        -  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

        -  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


Primary Outcome

4-month Progression-Free Survival Rate

Secondary Outcome

 Progression-Free Survival


Mucosal Lentiginous Melanoma



Study Arms / Comparison Groups

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.


* 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


Estimated Enrollment


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

          -  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




18 Years - N/A

Accepts Healthy Volunteers



F. Stephen Hodi, MD, , 

Location Countries

United States

Location Countries

United States

Administrative Informations



Organization ID


Responsible Party

Principal Investigator

Study Sponsor

Dana-Farber Cancer Institute


 Brigham and Women's Hospital

Study Sponsor

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

Verification Date

October 2018