DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more



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 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 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

Page last updated: August 23, 2015

-- advertisement -- The American Red Cross
 
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017