Clinical Trial: Study of Dovitinib (TKI258) in Adenoid Cystic Carcinoma

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: A Phase II Pilot Study of Dovitinib (TKI258) in Patients With Recurrent or Metastatic Adenoid Cystic Carcinoma.

Brief Summary: The purpose of this study is to improve survival of patients with recurrent or metastatic Adenoid Cystic Carcinoma (ACC). This study will test the efficacy of the investigational drug, TKI258, in treating ACC.

Detailed Summary: Adenoid cystic carcinoma (ACC) is an uncommon malignancy that arises in secretory glands. The most common sites for the disease are the major and minor salivary glands but these tumors may also arise in the nasal cavity, lacrimal gland, tracheobronchial tree, breast or vulva. The mainstay of treatment for localized ACC is surgical resection often followed by post-operative radiotherapy. Although this leads to an initially high rate of local control, the 5-year disease-free survival rate is 50-75%. In addition, a significant proportion of the patients develop distant metastases, most frequently in the lung. Compared to other malignancies, ACC tends to grow more slowly. Thus, patients often do well in the short-term but long-term prognosis remains guarded and most succumb to the disease within 10-15 years. To date, systemic therapies have proven to be largely ineffective against recurrent and metastatic ACC. Dovitinib is a broad-targeted-profiled RTK inhibitor active against these three RTKs (VEGF, FGF and PDGF) involved in tumor cell growth. Based on its potency as an inhibitor of these RTKs both in vitro and in vivo, and the compound's oral availability, several clinical trials of dovitinib are underway. This phase II trial will test the hypothesis that dovitinib will be active against this disease. The rationale is based on pre-clinical studies that suggest that dovitinib suppresses tumor growth by blocking constitutive signaling of the fibroblast growth factor receptor-1 (FGFR1) and animal studies in which the drug proved to be active against primary ACC xenografts.
Sponsor: University of Virginia

Current Primary Outcome: Determine the objective tumor response rate following treatment with TKI258 [ Time Frame: From enrollment up to 36months ]

Original Primary Outcome: Determine the objective tumor response rate following treatment with TKI258

Current Secondary Outcome:

• Estimate the progression-free survival following treatment with TKI258. [ Time Frame: From enrollment up to first progression event ]
• Describe the adverse event profile of TKI258 in subjects who have ACC. [ Time Frame: From enrollment up to 36months ]
• Explore changes in quality of life measurements during TKI258 treatment. [ Time Frame: From enrollment up to 36months ]
• Demonstrate the feasibility of measuring and analyzing TKI258 induced changes in the growth rate of adenoid cystic carcinomas. [ Time Frame: From enrollment up to 36months ]
  Collect descriptive data about the change in tumor growth rates as measured by the change point method. Tumor growth, TGO, is defined as the estimated slope from tumor measurements taken prior to treatment will be compared with TG1, tumor growth as defined by the estimated slope after treatment. Each patient's tumor growth profile will be allowed one change point, one slope measured from pre-study (-6 months to time 0, change point at time 0) and the other slope (time 0 to time 4 months). Change in slope will be assessed.
• Biomarker and biologic studies [ Time Frame: From enrollment up to 1month ]
  Assess archival tumor samples for the expression of MYB protein and chromosomal rearrangements of the MYB locus. Does MYB locus status correlate with disease regression?

Original Secondary Outcome:

• Estimate the progression-free survival following treatment with TKI258.
• Describe the adverse event profile of TKI258 in subjects who have ACC.
• Explore changes in quality of life measurements during TKI258 treatment.
• Demonstrate the feasibility of measuring and analyzing TKI258 induced changes in the growth rate of adenoid cystic carcinomas.
  Collect descriptive data about the change in tumor growth rates as measured by the change point method. Tumor growth, TGO, is defined as the estimated slope from tumor measurements taken prior to treatment will be compared with TG1, tumor growth as defined by the estimated slope after treatment. Each patient's tumor growth profile will be allowed one change point, one slope measured from pre-study (-6 months to time 0, change point at time 0) and the other slope (time 0 to time 4 months). Change in slope will be assessed.
• Biomarker and biologic studies
  Assess archival tumor samples for the expression of MYB protein and chromosomal rearrangements of the MYB locus. Does MYB locus status correlate with disease regression?

Dates:
Date Received: January 17, 2012
Date Started: March 2012
Date Completion:
Last Updated: October 26, 2016
Last Verified: October 2016