PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
AA Secord, Duke University Medical Center
ClinicalTrials.gov Identifier:
NCT00672295
First received: May 4, 2008
Last updated: December 27, 2012
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
Ovarian Cancer
Peritoneal Cancer
Fallopian Tube Cancer
Drug: Dasatinib, Paclitaxel, and Carboplatin
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Duke University:

Primary Outcome Measures:
  • To determine maximal tolerated dose (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To describe the toxicity of this combination of therapy [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To describe the pharmacokinetics and pharmacodynamics parameters related to this combination [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To describe the clinical activity as defined as the response rate (complete and partial response rate) and progression-free survival > 6 months [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To compare the SRC pathway microarray signature in pre and post-treatment cancer specimens [ Time Frame: 6 months ] [ Designated as safety issue: No ]
  • To evaluate SRC pathway downstream substrates, FAX, paxcillin, and CRK-L in pre and post-treatment cancer specimens [ Time Frame: 6 months ] [ Designated as safety issue: No ]

Enrollment: 11
Study Start Date: August 2007
Study Completion Date: November 2012
Primary Completion Date: September 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Dasatinib, paclitaxel,and carboplatin
Combination of dasatinib, paclitaxel,and carboplatin
Drug: Dasatinib, Paclitaxel, and Carboplatin

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.

Other Names:
  • Dasatinib
  • Paclitaxel
  • Carboplatin
  • Taxol
  • Paraplatin
  • Sprycel

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00672295

Locations
United States, Florida
Moffitt Cancer Center
Tampa, Florida, United States, 33612-9497
United States, North Carolina
Duke University Health System
Durham, North Carolina, United States, 27701
Sponsors and Collaborators
AA Secord
Investigators
Principal Investigator: Angeles A Secord, MD Duke University Health System
  More Information

Additional Information:
Publications:
Responsible Party: AA Secord, Associate Professor, Gynecologic Oncology, Duke University Medical Center
ClinicalTrials.gov Identifier: NCT00672295     History of Changes
Other Study ID Numbers: Pro00012282, 105821b, 9311-06-R0
Study First Received: May 4, 2008
Last Updated: December 27, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Duke University:
Ovarian Cancer
Peritoneal Cancer
Tubal Cancer
Fallopian Tube Cancer
Dasatinib
Sprycel
Paclitaxel
Taxol
Carboplatin
Paraplatin

Additional relevant MeSH terms:
Ovarian Neoplasms
Peritoneal Neoplasms
Fallopian Tube Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Abdominal Neoplasms
Digestive System Neoplasms
Digestive System Diseases
Peritoneal Diseases
Fallopian Tube Diseases
Carboplatin
Paclitaxel
Dasatinib
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Antineoplastic Agents, Phytogenic
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Protein Kinase Inhibitors

ClinicalTrials.gov processed this record on August 21, 2014