A Phase II Study of Dasatinib (NSC 732517) in Previously-Treated Patients With Metastatic Colorectal Cancer
Overview
- Phase
- Phase 2
- Intervention
- dasatinib
- Conditions
- Recurrent Colon Cancer
- Sponsor
- National Cancer Institute (NCI)
- Enrollment
- 19
- Locations
- 1
- Primary Endpoint
- Progression-free Survival Rate
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
This phase II trial is studying dasatinib to see how well it works in treating patients with previously treated metastatic colorectal cancer. Dasatinib may stop the growth of tumor cells by blocking some of the enzymes needed for their growth.
Detailed Description
PRIMARY OBJECTIVES: I. Determine the progression-free survival of patients with metastatic colorectal cancer who have progressed on or following two prior chemotherapy regimens and are then treated with dasatinib. SECONDARY OBJECTIVES: I. Determine the objective response rates in patients treated with dasatinib. II. Determine the overall survival of patients treated with dasatinib. III. Determine the toxicity in patients treated with dasatinib. TERTIARY OBJECTIVES: I. Determine the incidence of somatic mutations in c-src, c-yes, fyn, lck, hck, lyn, yrk and csk in archival primary and metastatic colorectal cancer tissues from these patients and to correlate this with clinical outcome. II. Determine the incidence of total c-src and phosphorylated c-src expression in archival primary and metastatic colorectal cancer specimens from these patients, and to correlate this with clinical outcome. III. Evaluate the effect of dasatinib on serum VEGF levels. OUTLINE: This is a multicenter study. Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Blood is collected on days 1 (prior to the first dose of dasatinib) and 15 of course 1 for measurement of VEGF pre-and post-dasatinib administration. Archived tumor tissue (tumor or core biopsy; primary or metastatic lesion) is collected for identification of the incidence of somatic mutations and polymorphisms by polymerase chain reaction and electrophoresis and for measurement of total c-src and phosphorylated src expression by immunohistochemistry. After completion of study treatment, patients are followed for at least 8 weeks.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histologically or cytologically confirmed colorectal cancer
- •Metastatic disease
- •Not curable by surgical resection
- •Archival tumor tissue available
- •Measurable disease, defined as at least one unidimensionally measurable lesion ≥ 20 mm by conventional techniques or ≥ 10 mm by spiral CT scan
- •Measurable disease must be outside of a prior radiation port
- •Documented disease progression either during or after prior chemotherapy treatment
- •No more than 2 prior chemotherapy regimens in the adjuvant or metastatic setting
- •Prior chemotherapy regimens must have contained a fluoropyrimidine (e.g., fluorouracil or capecitabine), oxaliplatin, and irinotecan
- •Patients who received no prior adjuvant therapy must have received 2 prior chemotherapy regimens for metastatic disease (e.g., FOLFOX followed by FOLFIRI)
Exclusion Criteria
- Not provided
Arms & Interventions
Treatment (tyrosine Kinase Inhibitor)
Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: dasatinib
Treatment (tyrosine Kinase Inhibitor)
Patients receive oral dasatinib twice daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Intervention: laboratory biomarker analysis
Outcomes
Primary Outcomes
Progression-free Survival Rate
Time Frame: From the start of treatment to the time of disease progression or death from any cause, assessed at 4 months after completion of treatment (i.e., up to 12 months.)
Progression will be evaluated in this study using the new international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Patients who are still alive and have not progressed will be censored at the date of the last negative examination. A Simon (1989), optimal, two-stage design will be employed. The progression-free survival count will be the proportion of subjects who are alive and progression-free at 4 months.
Secondary Outcomes
- Response Rate (RR) (Complete or Partial Responders)(Every 2 courses, assessed up to 8 weeks after completion of study treatment (i.e., up to 10 months))
- Incidence of Somatic Mutations(1 year)
- Association Between the Incidence of Total C-src and Phosphorylated C-src Expression and Response(4 months)
- Change in Plasma Vascular Endothelial Growth Factor (VEGF) Levels Over 15 Days(At baseline and day 15)