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

NCT ID: NCT00672295

Last Updated: 2012-12-28

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

PHASE1

Total Enrollment

11 participants

Study Classification

INTERVENTIONAL

Study Start Date

2007-08-31

Study Completion Date

2012-11-30

Brief Summary

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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

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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.

Conditions

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Ovarian Cancer Peritoneal Cancer Fallopian Tube Cancer

Keywords

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Ovarian Cancer Peritoneal Cancer Tubal Cancer Fallopian Tube Cancer Dasatinib Sprycel Paclitaxel Taxol Carboplatin Paraplatin

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Dasatinib, paclitaxel,and carboplatin

Combination of dasatinib, paclitaxel,and carboplatin

Group Type EXPERIMENTAL

Dasatinib, Paclitaxel, and Carboplatin

Intervention Type DRUG

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.

Interventions

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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.

Intervention Type DRUG

Other Intervention Names

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Dasatinib Paclitaxel Carboplatin Taxol Paraplatin Sprycel

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Eligible Sex

FEMALE

Accepts Healthy Volunteers

No

Sponsors

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AA Secord

OTHER

Sponsor Role lead

Responsible Party

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AA Secord

Associate Professor, Gynecologic Oncology

Responsibility Role SPONSOR_INVESTIGATOR

Principal Investigators

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Angeles A Secord, MD

Role: PRINCIPAL_INVESTIGATOR

Duke Health

Locations

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Moffitt Cancer Center

Tampa, Florida, United States

Site Status

Duke University Health System

Durham, North Carolina, United States

Site Status

Countries

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United States

References

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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.

Reference Type BACKGROUND
PMID: 22837181 (View on PubMed)

Related Links

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Other Identifiers

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105821b

Identifier Type: -

Identifier Source: secondary_id

9311-06-R0

Identifier Type: -

Identifier Source: secondary_id

Pro00012282

Identifier Type: -

Identifier Source: org_study_id