Clinical Trial: Dasatinib in Treating Patients With Recurrent or Metastatic Malignant Salivary Gland Tumors

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

Official Title: Phase II Trial of Dasatinib (BMS 354825) for Recurrent or Metastatic c-KIT Expressing Adenoid Cystic Carcinoma and Non-Adenoid Cystic Malignant Salivary Tumors

Brief Summary: This phase II trial is studying how well dasatinib works in treating patients with recurrent or metastatic malignant salivary gland tumors. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Detailed Summary:

PRIMARY OBJECTIVES:

I. Determine the objective response rate (complete and partial response) in patients with recurrent or metastatic c-KIT-expressing adenoid cystic carcinoma (ACC) of the salivary gland treated with dasatinib.

II. Determine the progression-free survival of these patients.

SECONDARY OBJECTIVES:

I. Determine the duration of response in patients with non-ACC or c-KIT-expressing ACC of the salivary gland.

II. Determine the stable disease rate and duration of stable disease in these patients.

III. Determine the median survival of these patients. IV. Determine the overall survival of these patients. V. Determine the safety and tolerability of dasatinib in these patients. VI. Determine the progression-free survival of patients with non-ACC of the salivary gland.

TERTIARY OBJECTIVES:

I. Correlate biomarkers that relate to Src signal transduction with clinical response to dasatinib in patients with non-ACC or c-KIT-expressing ACC of the salivary gland.

II. Determine if activating mutations in PDGFA and KIT are associated with response in patients with c-KIT-expressing ACC of the salivary gland.

OUTLINE: This is a multicenter study.

Patients are assigned to 1 of 2 cohorts according to histologic subtype (adenoid cystic carcinoma [ACC] vs non-ACC).

Patients receive oral dasatinib twice daily on days 1-28. Courses repeat every
Sponsor: National Cancer Institute (NCI)

Current Primary Outcome:

• Response Rate [ Time Frame: Up to 2 months ]
  Response rate is percentage of the best overall response which recoded from the start of the treatment until diseases progression/recurrence. Response criteria are defined using the international criteria proposed by the Response Evaluation Criteria In Solid Tumors (RECIST) Committee: Complete Response, Disappearance of all target lesions; Partial Response, >=30% decrease in the sum of the longest diameter of target lesions; Progressive Disease, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease, neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, no occurrence of progression disease for non-target lesions, and no new lesions.
• Progression-free Survival [ Time Frame: up to 5 years ]
  Progression-free survival from start of treatment to the time of disease progression or death from any cause was estimated using the Kaplan-Meier method.

Original Primary Outcome:

• Response rate
• Progression-free survival

Current Secondary Outcome:

• Overall Survival [ Time Frame: Up to 5 years ]
  Kaplan-Meier curves will be generated and 90% confidence intervals will be derived.
• Changes in Laboratory Correlates [ Time Frame: Baseline and 4 weeks ]
  Changes in laboratory correlates pre-post therapy will be analyzed using paired t-tests. The association between RET gene rearrangements/mutations and tumor response, as well as the association between germ-line polymorp response, will be analyzed using Fisher's exact test. The correlative and genetic data will also be entered as cova only due to the small sample size) in a Cox regression model of progression-free survival.

Original Secondary Outcome:

• Toxicity
• Time to progression
• Overall Survival
• Correlation between Src signal transduction biomarkers and clinical response to dasatinib
• Relationship between activating mutations in PDGFA and KIT and response to dasatinib

Dates:
Date Received: March 10, 2009
Date Started: March 2009
Date Completion:
Last Updated: November 1, 2016
Last Verified: November 2016