Brief Title
PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer
Official Title
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
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.
Detailed Description
This is a phase I multicenter study designed to determine the maximal tolerated dose (MTD)
and toxicity of dasatinib in combination with paclitaxel and carboplatin during the first
cycle of treatment in patients with advanced or recurrent ovarian, peritoneal, and tubal
carcinoma. The MTD will be defined as the highest dose at which no more than 1 of 6 evaluable
patient experiences a dose-limiting toxicity (DLT) due to the combination of dasatinib,
paclitaxel,and carboplatin during the first cycle of treatment.
Study Phase
Phase 1
Study Type
Interventional
Primary Outcome
To determine maximal tolerated dose (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment
Secondary Outcome
To describe the toxicity of this combination of therapy
Condition
Ovarian Cancer
Intervention
Dasatinib, Paclitaxel, and Carboplatin
Study Arms / Comparison Groups
Dasatinib, paclitaxel,and carboplatin
Description: Combination of dasatinib, paclitaxel,and carboplatin
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
11
Start Date
August 2007
Completion Date
November 2012
Primary Completion Date
September 2011
Eligibility Criteria
Inclusion Criteria:
- 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
Exclusion Criteria:
- 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
Gender
Female
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Angeles A Secord, MD, ,
Location Countries
United States
Location Countries
United States
Administrative Informations
NCT ID
NCT00672295
Organization ID
Pro00012282
Secondary IDs
105821b
Responsible Party
Sponsor-Investigator
Study Sponsor
AA Secord
Study Sponsor
Angeles A Secord, MD, Principal Investigator, Duke Health
Verification Date
December 2012