Second-Line Treatment for Patients With Platinum-Sensitive Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

Multicenter, Randomized, Phase II Comparative Study to Compare Efficacy & Safety of Taxotere®/Carboplatin Combination Therapy vs Sequential Therapy w/ Taxotere® Then Carboplatin as Second-line Treatment of Patients w/ Relapsed, Platinum-sensitive Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00090610
• Other study ID #: Pro00008381
• Secondary ID: DUKE UNIVERSITY
• Status: Completed
• Phase: Phase 2
• First received: August 27, 2004
• Last updated: February 5, 2015
• Start date: October 2003
• Est. completion date: October 2009

Study information

• Verified date: December 2012
• Source: Duke University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug AdministrationUnited States: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to compare the progression-free survival of two treatment regimens for relapsed ovarian cancer.

Description:

Primary Objective

The primary objective of the study is to compare the progression-free survival of two treatment regimens:

Taxotere® 30 mg/m2 IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days for 6 cycles or until disease progression. (A patient who has completed 6 cycles of treatment and who has achieved a partial response or stable disease may either continue or stop treatment at the investigator's discretion.)

Versus

Taxotere® 30 mg/m2 IV on Days 1 and 8, repeated every 21 days up to 6 cycles or until disease progression. Followed by carboplatin (AUC 6) IV every 21 days if the patient does not achieve a complete response or has disease progression on Taxotere®. A patient who has achieved a complete response on Taxotere® will be followed until the subsequent recurrence at which time she will then receive single-agent carboplatin. Carboplatin treatment will be discontinued if the patient has completed 6 cycles of treatment and has achieved a complete response or has disease progression. (A patient who has completed 6 cycles of carboplatin treatment and who has achieved a partial response or stable disease may either continue or stop treatment at the investigator's discretion.)

Secondary Objectives

The secondary objectives of the study are to compare the objective response rates (defined as a complete response plus partial response), duration of tumor response, median survival, QOL and safety in patients treated with the two regimens described above.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 150
• Est. completion date: October 2009
• Est. primary completion date: March 2009
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Pathologically confirmed epithelial ovarian cancer, peritoneal serous cancer, or tubal carcinoma.

• The patient's tumor is platinum-sensitive, which means that the patient had a complete response to front-line treatment with a platinum compound and had a treatment-free interval without clinical evidence of progressive disease for greater than 6 months.

• The patient has received one and only one prior chemotherapy regimen for the treatment of this malignancy. Prior treatment with paclitaxel and/or a platinum compound is allowed. Patients who have received consolidation treatment are allowed. Prior treatment with Taxotere® is not allowed.

o Consolidation therapy is allowed including a different cytotoxic agent than the agent used in the front-line regimen, intraperitoneal therapy, biologic therapy, and immunotherapy.

• Patients may have received one prior regimen with a biologic therapy, either combined with cytotoxic therapy in the front-line setting, or as a single-agent for this recurrence. The biologic therapy must be discontinued at least three weeks prior to registration.

• Measurable or evaluable disease either by radiologic imaging, or physical exam, or by measurement of CA125 < 70 on two occasions at least one week apart.

• At least 3 weeks since radiotherapy, with full recovery. The measurable disease must be completely outside the radiation portal.

• At least 3 weeks since major surgery, with full recovery. Patients who have undergone a secondary tumor debulking or cytoreductive surgery for this malignancy are excluded.

• Eastern Cooperative Oncology Group (ECOG) performance status < 2.

• Age > 18 years.

• Absolute neutrophil count > 1,500/mm3; platelet count > 100,000/mm3; Hemoglobin > 8.0 g/dl

• Serum bilirubin Within Normal Limits (WNL); AST or ALT and Alkaline Phosphatase must be within the range allowing for eligibility.

• If there is childbearing potential, a serum pregnancy test must be negative.

• Patients of childbearing potential must be willing to consent to using effective contraception while on treatment and for three months following the completion of treatment.

• Informed consent has been obtained.

Exclusion Criteria:

• Prior treatment with Taxotere®.

• Concurrent immunotherapy or hormonal therapy for the specific purpose of treatment for the disease. Any hormonal therapy directed at the malignant tumor must be discontinued at least one week prior to enrollment in order for the patient to be eligible to participate in this trial. Continuation of Hormone Replacement therapy is permitted.

• Serious concurrent medical or psychiatric illness, including serious active infection.

• Peripheral neuropathy > grade 2.

• History of other malignancy within the last 5 years, except for basal cell skin carcinoma.

• The patient is pregnant or nursing.

• Patients with a history of severe hypersensitivity reaction to cisplatin, carboplatin, mannitol, or drugs formulated with Polysorbate 80.

• Secondary debulking for this recurrence.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• Docetaxel
For Arm 1: 30mg/m2 mg IV on Days 1 and 8 repeated every 21 days for six cycles until disease progression combined with carboplatin For Arm 2: 30mg/m2 IV on Days 1 and 8 repeated every 21 days for six cycles until disease progression followed by carboplatin
• Carboplatin
Arm 1: AUC 6 IV on Days 1 and 8, repeated every 21 days for 6 cycles or until disease progression, combined with docetaxel. Arm 2: AUC 6 IV every 21 days for 6 cycles or until disease progression, following six cycles of treatment with docetaxel

Locations

Country	Name	City	State
United States	Hope: A Woman's Cancer Center	Asheville	North Carolina
United States	Southwest Regional Cancer Center	Austin	Texas
United States	Franklin Square Hospital Center/MedStar Health-Section of Hematology/Oncology	Baltimore	Maryland
United States	Hematology-Onc. Assoc. of The Quad Cities	Bettendorf	Iowa
United States	University of North Carolina/ Division of Gyn Oncology	Chapel Hill	North Carolina
United States	MUSC-Div of Gyn/Oncology	Charleston	South Carolina
United States	Carolinas Medical Center/Gyn Oncology Department	Charlotte	North Carolina
United States	Duke University/Division of Gynecologic Oncology	Durham	North Carolina
United States	Florida Gynecologic Oncology	Fort Myers	Florida
United States	Cancer Center at Hackensack	Hackensack	New Jersey
United States	University of Iowa	Iowa City	Iowa
United States	Jupiter Medical Center-Gynecology Oncology and Gynecology	Jupiter	Florida
United States	The West Cancer Clinic	Memphis	Tennessee
United States	Columbia University College of Physicians and Surg	New York	New York
United States	Gynecologic Oncology and Surgery	Oklahoma City	Oklahoma
United States	Florida Hospital/Gyn/Onc Department	Orlando	Florida
United States	PA Hematology/Oncology Associates	Philadelphia	Pennsylvania
United States	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania
United States	Forsyth Regional Cancer Center	Winston-Salem	North Carolina

Sponsors (2)

Lead Sponsor	Collaborator
Duke University	Aventis Pharmaceuticals

Country where clinical trial is conducted

United States, 

References & Publications (3)

Alvarez Secord A, Berchuck A, Higgins RV, Nycum LR, Kohler MF, Puls LE, Holloway RW, Lewandowski GS, Valea FA, Havrilesky LJ. A multicenter, randomized, phase 2 clinical trial to evaluate the efficacy and safety of combination docetaxel and carboplatin an — View Citation

Havrilesky LJ, Pokrzywinski R, Revicki D, Higgins RV, Nycum LR, Kohler MF, Berchuck A, Myers ER, Secord AA. Cost-effectiveness of combination versus sequential docetaxel and carboplatin for the treatment of platinum-sensitive, recurrent ovarian cancer. Ca — View Citation

Pokrzywinski R, Secord AA, Havrilesky LJ, Puls LE, Holloway RW, Lewandowski GS, Higgins RV, Nycum LR, Kohler MF, Revicki DA. Health-related quality of life outcomes of docetaxel/carboplatin combination therapy vs. sequential therapy with docetaxel then ca — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression-free Survival (PFS)	Progression in measurable disease is defined as any of the following: At least a 20% increase in the sum of the longest diameter target lesions; appearance of one or more new lesions; Death due to disease without prior objective documentation of progression; deterioration in health status attributable to the disease requiring a change in therapy without objective documentation of progression; Progression in non-measurable disease according to CA125 levels is defined as any of the following: CA125 that begins in normal range increases to twice the upper limit of normal; CA125 level that begins elevated increases 25% over two previous samples, a 50% increase over three previous samples, or a persistent elevation over 100 U/ml for more than 2 months without a 50% decrease.	Every 6 months, to 18 months	No
Secondary	Objective Response Rate	Complete response rate plus partial response rate, where: Complete response (CR) is defined as disappearance of all target and non-target lesions and no evidence of new lesions documented by two disease assessments at least 4 weeks apart and normalization of elevated CA125 in cases of ovarian cancer; Partial response (PR) for measurable disease is defined >= 30% decrease in the sum of the longest dimensions of all target measurable lesions with no unequivocal progression of non-target lesions as well as no new lesions, with documentation by two disease assessments at least four weeks apart. PR according to CA125 levels is defined as a 50% decrease in CA125 levels where two initial samples were elevated and the sample that shows the 50% is confirmed by a fourth sample 28 days after the prior sample.; OR = CR + PR	Every 6 months, starting at 12 months to 24 months	No
Secondary	Quality of Life	Quality of Life was measured using the Trial Outcome Index (TOI) score of the Functional Assessment of Cancer Therapy-Ovarian (FACT-O) instrument, version 4. The TOI portion of the FACT-O included questions related to Physical well-being (PWB), Social/Family well-being (FWB), and an ovarian cancer specific module (OCS). The PWB score range is from 0-28; the FWB score range is from 0-28; the OCS score range is from 0-44; this gives the TOI a score range from 0-100. (TOI = PWB + FWB + OCS); With these instruments, a higher score indicates better health-related quality of life.	Baseline performed 14 days before first dose, then every other cycle and at study termination	No
Secondary	Recurrence-Free Survival	Recurrence-free survival is based on measurable disease using Kaplan-Meier estimates for the intent to treat (ITT) Population who achieved a complete response.	Every 6 months starting at 12 months, to 24 months	No
Secondary	Median Overall Survival		Every 6 months starting at 12 months, to 24 months	No