PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer
A Phase I Trial of A SRC Kinase Inhibitor, Dasatinib,in Combination With Paclitaxel and Carboplatin in Patients With Advanced or Recurrent Ovarian, Peritoneal, and Tubal Cancer
3 other identifiers
interventional
11
1 country
2
Brief Summary
Primary objective to determine the maximal tolerated (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment. Secondary objectives to describe the toxicity of this combination of therapy; to describe the pharmacokinetics and pharmacodynamics parameters related to this combination; to describe the clinical activity as defined as the response rate (complete and partial response rate) and progression-free survival \> 6 month; to compare the SRC pathway microarray signature in pre and post-treatment cancer specimens; to evaluate SRC pathway downstream substrates, FAX, paxcillin, and CRK-L in pre and post-treatment cancer specimens.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for phase_1 ovarian-cancer
Started Aug 2007
Typical duration for phase_1 ovarian-cancer
2 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 1, 2007
CompletedFirst Submitted
Initial submission to the registry
May 4, 2008
CompletedFirst Posted
Study publicly available on registry
May 6, 2008
CompletedPrimary Completion
Last participant's last visit for primary outcome
September 1, 2011
CompletedStudy Completion
Last participant's last visit for all outcomes
November 1, 2012
CompletedDecember 28, 2012
December 1, 2012
4.1 years
May 4, 2008
December 27, 2012
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
To determine maximal tolerated dose (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment
6 months
Secondary Outcomes (5)
To describe the toxicity of this combination of therapy
6 months
To describe the pharmacokinetics and pharmacodynamics parameters related to this combination
6 months
To describe the clinical activity as defined as the response rate (complete and partial response rate) and progression-free survival > 6 months
6 months
To compare the SRC pathway microarray signature in pre and post-treatment cancer specimens
6 months
To evaluate SRC pathway downstream substrates, FAX, paxcillin, and CRK-L in pre and post-treatment cancer specimens
6 months
Study Arms (1)
Dasatinib, paclitaxel,and carboplatin
EXPERIMENTALCombination of dasatinib, paclitaxel,and carboplatin
Interventions
Dasatinib will be administered as an oral dose (tablet) as per the dose escalation (50 mg everyday - 250 mg everyday)continuously on days 2-21 in the first cycle (3 weeks) therapy and continuously (days 1-21) throughout the remainder of therapy. Paclitaxel will be administered on a 21-day schedule. Paclitaxel (150-175 mg/m\^2) IV infused over 3 hours on day #1 of each cycle. Carboplatin (AUC=5-6 mg/,l/min) will be infused over 30-60 minutes every cycle via IV on day 1 of every cycle following the paclitaxel administration. All patients will be followed until disease progression or study withdrawal. In addition, following disease progression, patients will be monitored for delayed toxicity and survival for a period of 5 years and data entered into eDC, unless is withdrawn.
Eligibility Criteria
You may qualify if:
- Pts must have histologic or cytologic evidence of ovarian, peritoneal, or tubal cancer
- All pts must have measurable disease
- \> 18 yrs
- Expected survival of at least 3 months
- Pts must have GOG performance status pf 0, 1 or 2
- Pts must have adequate:Bone marrow function, renal function, hepatic function, neurologic function
- No chemo, radiotherapy, biologic, hormonal, or investigational drug therapy within 28 days prior to study entry
- Pts may have had up to 3 prior cytotoxic chemo regimens including prior treatment w carboplatin \& paclitaxel
- Capable of providing written informed consent
- Pts of childbearing potential must have negative serum pregnancy test prior to study entry \& be practicing effective method of birth control during course of study, in manner such that risk of failure is minimized. Prior to study enrollment, women of childbearing potential must be advised of importance of avoiding pregnancy during trial participation \& potential risk factors for unintentional pregnancy
- Pts must have tissue block from their tumor available for evaluation for microarray \& immunoblot analyses. Pretreatment tumor tissue may be obtained from either archival tissue or be obtained by guided by guided core needle or simple biopsy it must be performed within four weeks prior to enrollment on study. Pts must have tumor that is accessible to biopsy \& consent to undergo post-treatment biopsy after cycle #2 of treatment as well
You may not qualify if:
- Pts w epithelial ovarian tumors of low malignant potential (borderline tumor)
- Pts w history of other invasive malignancies, w exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within last 5 yrs
- Pts who have following cardiac conditions: uncontrolled angina or myocardial infarction within past 6 months; diagnosed or suspected congenital long QT syndrome; Any history of clinically significant ventricular arrhythmias; Prolonged QTc interval on pre-entry electrocardiogram on both Fridericia \& Bazett's correction; uncontrolled hypertension
- History of significant bleeding disorder unrelated to cancer, including: diagnosed congenital bleeding disorders; diagnosed acquired bleeding disorder within 1 yr
- Pts currently taking drugs that are generally accepted to have risk of causing Torsades de Pointes including: quinidine, procainamide, disopyramide; amiodarone, sotalol, ibutilide, dofetilide; erythromycins, clarithromycin; chlorpromazine, haloperidol, mesoridazine, thioridazine, pimozide; cisapride, bepridil, droperidol, methadone, arsenic, chloroquine, domperidone, halofantrine, levomethadyl, pentamidine, sparfloxacin, lidoflazine
- Serum creatinine \> 1.5 times institutional upper limits of normal
- Pts taking certain concomitant medications, consider following prohibitions: medications that inhibit platelet function or anticoagulants
- Pts who have received radiation therapy to \> 30 percent of bone marrow
- Pts w history of grade 3 hypersensitivity to paclitaxel or carboplatin
- Pts w septicemia, severe infection, acute hepatitis, other uncontrolled severe medical conditions
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- AA Secordlead
Study Sites (2)
Moffitt Cancer Center
Tampa, Florida, 33612-9497, United States
Duke University Health System
Durham, North Carolina, 27701, United States
Related Publications (1)
Secord AA, Teoh DK, Barry WT, Yu M, Broadwater G, Havrilesky LJ, Lee PS, Berchuck A, Lancaster J, Wenham RM. A phase I trial of dasatinib, an SRC-family kinase inhibitor, in combination with paclitaxel and carboplatin in patients with advanced or recurrent ovarian cancer. Clin Cancer Res. 2012 Oct 1;18(19):5489-98. doi: 10.1158/1078-0432.CCR-12-0507. Epub 2012 Jul 26.
PMID: 22837181BACKGROUND
Related Links
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Angeles A Secord, MD
Duke Health
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- OTHER
- Responsible Party
- SPONSOR INVESTIGATOR
- PI Title
- Associate Professor, Gynecologic Oncology
Study Record Dates
First Submitted
May 4, 2008
First Posted
May 6, 2008
Study Start
August 1, 2007
Primary Completion
September 1, 2011
Study Completion
November 1, 2012
Last Updated
December 28, 2012
Record last verified: 2012-12