Clinical trial NCT00672295: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Keywords: Ovarian Cancer
Peritoneal Cancer
Tubal Cancer
Fallopian Tube Cancer
Dasatinib
Sprycel
Paclitaxel
Taxol
Carboplatin
Paraplatin
Lead sponsor: Duke University
Sponsor class: OTHER
First posted: 2008-05-06
Enrollment: 11
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: To determine maximal tolerated dose (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment
timeFrame: 6 months
Secondary outcomes:
measure: To describe the toxicity of this combination of therapy
timeFrame: 6 months
measure: To describe the pharmacokinetics and pharmacodynamics parameters related to this combination
timeFrame: 6 months
measure: To describe the clinical activity as defined as the response rate (complete and partial response rate) and progression-free survival > 6 months
timeFrame: 6 months
measure: To compare the SRC pathway microarray signature in pre and post-treatment cancer specimens
timeFrame: 6 months
measure: To evaluate SRC pathway downstream substrates, FAX, paxcillin, and CRK-L in pre and post-treatment cancer specimens
timeFrame: 6 months
Other outcomes:
Locations:
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Durham
country: United States
facility: Duke University Health System
state: North Carolina
Study officials:
affiliation: Duke Health
name: Angeles A Secord, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.