TORI 104 Pre-Surgical Dasatinib
|First Received Date ICMJE||August 4, 2011|
|Last Updated Date||August 4, 2011|
|Start Date ICMJE||Not Provided|
|Primary Completion Date||Not Provided|
|Current Primary Outcome Measures ICMJE||Not Provided|
|Original Primary Outcome Measures ICMJE||Not Provided|
|Change History||No Changes Posted|
|Current Secondary Outcome Measures ICMJE||Not Provided|
|Original Secondary Outcome Measures ICMJE||Not Provided|
|Current Other Outcome Measures ICMJE||Not Provided|
|Original Other Outcome Measures ICMJE||Not Provided|
|Brief Title ICMJE||TORI 104 Pre-Surgical Dasatinib|
|Official Title ICMJE||A Pre-Surgical Study to Evaluate Molecular Changes That Occur in Human Breast Cancer Tissue After Short Term Exposure to Dasatinib and To Correlate These Alterations With Pharmacokinetics Parameters|
This study will examine the anti-tumor activity, safety and tolerability of dasatinib in adjuvant breast cancer patients in a pre-surgical setting.
Primary Objective: To evaluate the molecular changes which occur in human breast cancer tissue after short-term exposure to dasatinib.
" To evaluate the molecular effects of short term dasatinib exposure in peripheral blood and on SRC (an oncogene) and EPHA2 signaling pathways in non-tumor cells (peripheral blood).
" To correlate the pharmacokinetic parameters with molecular changes detected in breast cancer tissues and peripheral blood " To evaluate the tolerability and safety of short-term exposure to daily dose of 100 mg twice daily of dasatinib administration
Eligible patients will be registered to receive dasatinib 100 mg orally twice daily starting within 8 days from the time of registration and continuing to the time of the definitive surgery.
Duration of Treatment " No more than 8 days should elapse from the time of registration to the time of the first dose of dasatinib " No more than 28 days should elapse from the time of the initial diagnosis to the time of the first dose of dasatinib " Minimum duration of treatment with dasatinib is 14 days with a minimum of 10 consecutive days of treatment immediately prior to the definitive surgery " Dasatinib shall be administered until the day prior to the definitive surgery " No more than 45 days should elapse from the time of the initial diagnosis to the time of the definitive surgery i.e. maximum duration of treatment with dasatinib is 45 days.
Core Biopsies: Tumor sample must be collected at the time of the initial diagnosis (or in a subsequent procedure) either by core needle or incisional biopsy. Excisional biopsy will not be allowed. A minimum of 4 core biopsies (or the equivalent with an incisional biopsy) is required to perform the molecular analyses. Once the core biopsies have been removed, the samples must be immediately snap-frozen, then stored in liquid nitrogen or at -70 to -80 C at the site. Samples will be shipped to the UCLA laboratory within 30 days of collection.
Tumor Tissue at the time of Definitive Surgery: A second tumor sample (post-dasatinib) must be collected at the time of the patient's surgery in the same manner as above.
Unstained paraffin slides: While most analyses will be performed on the frozen tissue, some molecular testing may require paraffin embedded tissue. The pathology department will be asked to send 4, 5 micron thick, unstained paraffin slides of each the pretreatment (diagnosis biopsy) and from the definitive surgery (8 slides in total) Definitive Surgery: The type of definitive surgery performed will be according to the institution's guidelines. In the event that a sentinel node biopsy procedure is performed, the dye can be injected into the tumor bed after tumor removal. The dye should not be injected into the tumor itself as this may alter the tissue and affect the molecular analyses.
Pharmacokinetic plasma samples and peripheral blood mononuclear cells samples will be collected at the following time points (5 samples each):
Samples from all patients are required to all for the relatively large variability in dasatinib pharmacokinetics (interpatient coefficient of variation is approximately 65 %) The samples will be centrifuged, processed, and shipped. Results from the pharmacokinetics analysis will be correlated with the molecular data.
Number of Patients: 60 evaluable patients
The primary objective of this trial is to evaluate molecular changes occurring in breast cancer tissue following short-term dasatinib administration. Based on pre-clinical data supporting the role of Src in "triple-negative" breast cancer, the study will aim for 50% of evaluable patients be of this subtype defined as being negative for ER, PR, and HER2 amplification. In cases where HER2 amplification is not determined by FISH at diagnosis, HER2 staining by IHC of 0 or 1+ will be considered negative for enrolment purposes. After 30, 40, and 50 evaluable patients have been accrued, enrolment may be adjusted to reach the goal of 30 triple-negative patients.
Descriptive statistics will be used to compare the pre- and post-treatment molecular findings. A statistical Analysis Plan (SAO) will be finalized at the latest prior to database lock and the analysis details will be provided in the SAP. Descriptive statistics will be used to describe the incidence of adverse events and toxicity, as well as the number of patients in who the study medication was permanently stopped.
Enrolment is completed according to protocol planned sample size, and assessments and requirements are completed as per protocol, the stated objectives of the trial are achieved, recommendation by DMC. Patients may withdraw from the trial at any time at their own request, or they may be withdrawn at any time at the discretion of the investigator or sponsor if continuation of the study would be detrimental to the patient's well being, such as objective disease progression, unacceptable toxicity, noncompliance, second primary malignancy, or logistical considerations
|Study Type ICMJE||Interventional|
|Study Phase||Phase 2|
|Study Design ICMJE||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Condition ICMJE||Breast Cancer|
|Intervention ICMJE||Drug: Dasatinib|
|Study Arm (s)||Not Provided|
|Publications *||Not Provided|
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
|Recruitment Status ICMJE||Withdrawn|
|Estimated Enrollment ICMJE||60|
|Completion Date||Not Provided|
|Primary Completion Date||Not Provided|
|Eligibility Criteria ICMJE||
|Ages||18 Years and older|
|Accepts Healthy Volunteers||No|
|Contacts ICMJE||Contact information is only displayed when the study is recruiting subjects|
|Location Countries ICMJE||Canada|
|NCT Number ICMJE||NCT01410708|
|Other Study ID Numbers ICMJE||BR-1-0103, TORI 104|
|Has Data Monitoring Committee||Yes|
|Responsible Party||Not Provided|
|Study Sponsor ICMJE||Alberta Health Services|
|Collaborators ICMJE||Not Provided|
|Investigators ICMJE||Not Provided|
|Information Provided By||Alberta Health Services|
|Verification Date||August 2011|
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP