PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer
Primary Purpose
Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
Dasatinib, Paclitaxel, and Carboplatin
Sponsored by
About this trial
This is an interventional treatment trial for Ovarian Cancer focused on measuring Ovarian Cancer, Peritoneal Cancer, Tubal Cancer, Fallopian Tube Cancer, Dasatinib, Sprycel, Paclitaxel, Taxol, Carboplatin, Paraplatin
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
Sites / Locations
- Moffitt Cancer Center
- Duke University Health System
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Dasatinib, paclitaxel,and carboplatin
Arm Description
Combination of dasatinib, paclitaxel,and carboplatin
Outcomes
Primary Outcome Measures
To determine maximal tolerated dose (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment
Secondary Outcome Measures
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
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00672295
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
Study Type
Interventional
2. Study Status
Record Verification Date
December 2012
Overall Recruitment Status
Completed
Study Start Date
August 2007 (undefined)
Primary Completion Date
September 2011 (Actual)
Study Completion Date
November 2012 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor-Investigator
Name of the Sponsor
AA Secord
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ovarian Cancer, Peritoneal Cancer, Fallopian Tube Cancer
Keywords
Ovarian Cancer, Peritoneal Cancer, Tubal Cancer, Fallopian Tube Cancer, Dasatinib, Sprycel, Paclitaxel, Taxol, Carboplatin, Paraplatin
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
11 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Dasatinib, paclitaxel,and carboplatin
Arm Type
Experimental
Arm Description
Combination of dasatinib, paclitaxel,and carboplatin
Intervention Type
Drug
Intervention Name(s)
Dasatinib, Paclitaxel, and Carboplatin
Other Intervention Name(s)
Dasatinib, Paclitaxel, Carboplatin, Taxol, Paraplatin, Sprycel
Intervention Description
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.
Primary Outcome Measure Information:
Title
To determine maximal tolerated dose (MTD) of dasatinib in combination with paclitaxel and carboplatin during the first cycle of treatment
Time Frame
6 months
Secondary Outcome Measure Information:
Title
To describe the toxicity of this combination of therapy
Time Frame
6 months
Title
To describe the pharmacokinetics and pharmacodynamics parameters related to this combination
Time Frame
6 months
Title
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
Title
To compare the SRC pathway microarray signature in pre and post-treatment cancer specimens
Time Frame
6 months
Title
To evaluate SRC pathway downstream substrates, FAX, paxcillin, and CRK-L in pre and post-treatment cancer specimens
Time Frame
6 months
10. Eligibility
Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Angeles A Secord, MD
Organizational Affiliation
Duke Health
Official's Role
Principal Investigator
Facility Information:
Facility Name
Moffitt Cancer Center
City
Tampa
State/Province
Florida
ZIP/Postal Code
33612-9497
Country
United States
Facility Name
Duke University Health System
City
Durham
State/Province
North Carolina
ZIP/Postal Code
27701
Country
United States
12. IPD Sharing Statement
Citations:
PubMed Identifier
22837181
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.
Results Reference
background
Links:
URL
http://obgyn.duke.edu
Description
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PH I SRC Kinase, Dasatinib Combo Paclitaxel & Carboplatin in Pts w Ovarian, Peritoneal, & Tubal Cancer
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