Phase II Study of Dasatinib in Previously Treated Patients With Advanced NSCLC (TOP0801)
On this study patients will receive dasatinib, a targeted therapy, for advanced NSCLC that has progressed after previous therapy. Safety and response to dasatinib will be assessed.
Fresh frozen tumor tissue must be available for genomics analysis prior to initiating dasatinib therapy. A biopsy must be obtained after any prior chemotherapy. If fresh frozen tumor tissue is not available, a biopsy will be required to participate in this trial.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Dasatinib in Previously Treated Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)|
- Tumor Response [ Time Frame: 2 years ] [ Designated as safety issue: No ]
Tumor response rate was defined by RECIST criteria:
CR (complete response) = disappearance of all target lesions taking as reference the baseline sum of the longest diameter (LD); PR (partial response) = at least a 30% decrease in the sum of the longest diameter of target lesions; PD (progressive disease) = at least a 20% increase in the sum of the longest diameter of target lesions as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions; SD (stable disease) = Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum LD since the treatment started
- Overall Survival [ Time Frame: Progression and survival every 6 months ] [ Designated as safety issue: No ]Overall survival (OS) is the duration from date of consent to date of death from any cause.
- Grade 3-5 Toxicity Associated With Dasatinib Treatment [ Time Frame: Duration of dasatinib treatment plus 30 days ] [ Designated as safety issue: Yes ]Number of subjects with Grade 3-5 toxicity as assessed using NCI CTCAE criteria with the attribution of possibly, probably, or definitely related to protocol treatment.
- Describe Change in Serum Levels of C-terminal Cross-linked Collagen I Between Pre-treatment and 6 Weeks After Starting Dasatinib. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
- Determine Relationship Between K-ras Gene Mutation and Response to Dasatinib. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
|Study Start Date:||September 2008|
|Study Completion Date:||June 2013|
|Primary Completion Date:||June 2013 (Final data collection date for primary outcome measure)|
After a biopsy is done to obtain fresh frozen tumor tissue (Stage I), dasatinib is to be administered as an oral dose of 70 mg twice daily on a continuous basis for 6 weeks. Every 6 weeks radiologic exam will be done to assess response. Treatment will continue until progression of disease, intolerable toxicity or patient withdrawal.
For Stage II, a biopsy to obtain fresh frozen tumor tissue will also be done. Depending on results from Stage I and results of biopsy, treatment with dasatinib will be determined.
70 mg PO twice daily until progression. Re-assess radiographically every 6 weeks.
Other Name: Sprycel
Lung cancer is the leading cause of cancer death in the United States. Twenty to seventy-five percent of patients initially treated with surgery or radiotherapy recur and become candidates for systemic therapy. Src expression has been identified in a majority of NSCLC cell lines and may be important in hypoxic growth and angiogenesis of NSCLC.
This phase II trial will investigate the activity of the oral Src inhibitor dasatinib in advanced stage NSCLC. We hypothesize that the inhibition of Src pathway with dasatinib will show anti-tumor activity in advanced NSCLC, with a tolerable safety profile.
Fresh frozen tissue is needed for the genomics analysis, thus a biopsy will be required to participate in this trial. The genomic analysis will determine if the tumor is Src-active or Src-inactive and responses to dasatinib compared. In stage I, 40 patients will be treated without prior knowledge of their tumoral Src-activity. If all stage I responses are observed in the Src-active patients, the second stage will only accrue that cohort. If all responses are observed in the Src-inactive cohort, the activity of dasatinib and genomic determination of dasatinib response will be re-evaluated. Otherwise, if during Stage I, responses are observed in both cohorts, they will be accrued separately and evaluated in a two-stage manner.
Dasatinib will be give orally twice daily and continue until progression of disease, intolerable toxicity or patient withdrawal. Imaging studies will be done pre-treatment then every 6 weeks to assess radiologic response to therapy.
Patients will be followed for 30 days after the last dose of dasatinib to assess toxicity.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00787267
|United States, North Carolina|
|Duke University Medical Center|
|Durham, North Carolina, United States, 27710|
|Durham VA Medical Center|
|Durham, North Carolina, United States, 27705|
|Raleigh, North Carolina, United States, 27609|
|Principal Investigator:||Michael Kelley, MD||Duke University|