PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer
Information source: Duke University
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Ovarian Cancer; Peritoneal Cancer; Fallopian Tube Cancer
Intervention: Dasatinib, Paclitaxel, and Carboplatin (Drug)
Phase: Phase 1
Status: Completed
Sponsored by: AA Secord Official(s) and/or principal investigator(s): Angeles A Secord, MD, Principal Investigator, Affiliation: Duke University Health System
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.
Clinical Details
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
Study design: Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
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 therapyTo 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 months 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.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Female.
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
Locations and Contacts
Moffitt Cancer Center, Tampa, Florida 33612-9497, United States
Duke University Health System, Durham, North Carolina 27701, United States
Additional Information
Related publications: 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.
Starting date: August 2007
Last updated: December 27, 2012
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