Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Acral Lentiginous Melanoma

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Cohort A participants received 50 mg sunitinib orally daily for 4 weeks followed by a two-week break from treatment. These 6-week cycles would be repeated until progression or unacceptable toxicity up to 1 year.

Cohort B participants received 37.5 mg sunitinib daily on a continuous basis until progression or unacceptable toxicity up to 1 year.

F. Stephen Hodi, MD

The purpose of this study is to evaluate how effective Sunitinib works in treating acral lentiginous and mucosal melanoma which has spread beyond the local region. Suninitib is a protein-tyrosine kinase inhibitor and acts as a c-kit inhibitor drug. It is believed to work by blocking signals on certain cancer cells which allow the malignant cells to multiply and spread due to a change in the genetic make up of the cancer cell.

OBJECTIVES:

Primary

* To determine the proportion of participants with metastatic mucosal or acral/lentiginous melanoma who are alive and without disease progression at two months after beginning treatment with sunitinib.
* To determine the best overall response rate.

Secondary

* To determine the time to progression and overall survival.
* To correlate c-kit mutational status with response to therapy.
* To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
* To assess amplification of c-kit status through quantitative PCR and/or FISH and other related molecular pathway targets.

SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

A Phase II Study of SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma

2-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 2 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.

The best overall response rate was defined as achieving partial response (PR) or complete response (CR) on treatment based on RECIST 1.0 criteria. Per RECIST 1.0 for target lesions, CR is complete disappearance of all target lesions and PR is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. To be assigned a status of CR or PR, changes in tumor measurements must be confirmed by repeat assessments performed no fewer than 4 weeks after the response criteria are first met. PR or better overall response assumes at a minimum incomplete response/stable disease (SD) for the evaluation of non-target lesions and absence of new lesions.

Overall survival (OS) is defined as the time from study entry to death or date last known alive.

Time to progression 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. 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.

Beth Israel Deaconess Medical Center

Massachusetts General Hospital

Pfizer

Dana-Farber Cancer Institute

Melanoma Disease Center Director

Maximum grade toxicity by type was first calculated. Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv3. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv3.

Cohort A participants received 50 mg sunitinib orally daily for 4 weeks followed by a two-week break from treatment. These 6-week cycles would be repeated until progression or unacceptable toxicity up to 1 year.

Cohort A-Sunitinib Intermittent Dosing

Cohort B participants received 37.5 mg sunitinib daily on a continuous basis until progression or unacceptable toxicity up to 1 year.

Cohort B-Sunitinib Continuous Dosing

Total

Age, Continuous

Sex: Female, Male

Race (NIH/OMB)

United States

Region of Enrollment

The analysis dataset is comprised of treated patients.

2-month Progression-free Survival Rate

Best Overall Response Rate

Overall Survival

The analysis dataset is comprised of treated patients. The majority of patients were off-treatment due to disease progression and thus the relevant observation time frame for this outcome is time on treatment.

Time to Progression

Overall Study

Amino Acids

Nilotinib

Tyrosine Kinase Inhibitors

Tyrosine

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.

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.

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.

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

A Phase II Study of Nilotinib (AMN107) In TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral or Chronically Sun Damaged Melanoma

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.

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.

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.

Brigham and Women's Hospital

Novartis

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. Patients were classified into two cohorts based upon presence or absence of measurable brain metastases.

No CNS Metastastic Cohort

CNS Metastatic Cohort

Ethnicity (NIH/OMB)

Acral

Mucosal

Chronically Sun-Damaged (CSD)

Melanoma Type

Eastern Cooperative Oncology Group (ECOG) PS: (PS0) Fully active, able to carry on all pre-disease performance without restriction (PS1) Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (PS2) Ambulatory and capable of all self-care but unable to carry out any work activities; Up and about \>50% of waking hours

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization	Link
SU011248 in Patients With Metastatic Mucosal or Acral/Lentiginous Melanoma	NCT00577382	Mucosal Lentigi... Acral Lentigino...	Sunitinib	18 Years -	Dana-Farber Cancer Institute
Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma	NCT00788775	Mucosal Lentigi... Acral Melanoma Melanoma	Nilotinib	18 Years -	Dana-Farber Cancer Institute

Spots Global Cancer Trial Database for mucosal lentiginous melanoma