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

• Sponsor: Duke University (Other)
• Overall Status: Completed
• CT.gov ID: NCT00090610
• Collaborator: Aventis Pharmaceuticals (Industry)
• Enrollment: 150
• Locations: 19
• Arms: 2
• Duration (Months): 72
• Patients Per Site: 7.9
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

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

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: Docetaxel; Drug: Carboplatin	Phase 2

Detailed 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.

Study Design

• Study Type: Interventional
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• 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
• Study Start Date: Oct 1, 2003
• Actual Primary Completion Date: Mar 1, 2009
• Actual Study Completion Date: Oct 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 - Combination Therapy Docetaxel 30mg/m2 mg IV on Days 1 and 8, in combination with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	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; Other Names: Taxotere ; Drug: 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; Other Names: Paraplatin
Experimental: Arm 2 - Sequential Therapy Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression. Once subjects have completed 6 cycles of docetaxel, they receive carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.	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; Other Names: Taxotere ; Drug: 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; Other Names: Paraplatin

Outcome Measures

Primary Outcome Measures

1. Progression-free Survival (PFS) [Every 6 months, to 18 months]

   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.

Secondary Outcome Measures

1. Objective Response Rate [Every 6 months, starting at 12 months to 24 months]

   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

2. Quality of Life [Baseline performed 14 days before first dose, then every other cycle and at study termination]

   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.

3. Recurrence-Free Survival [Every 6 months starting at 12 months, to 24 months]

   Recurrence-free survival is based on measurable disease using Kaplan-Meier estimates for the intent to treat (ITT) Population who achieved a complete response.

4. Median Overall Survival [Every 6 months starting at 12 months, to 24 months]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Florida Gynecologic Oncology	Fort Myers	Florida	United States	33901
2	Jupiter Medical Center-Gynecology Oncology and Gynecology	Jupiter	Florida	United States	33458
3	Florida Hospital/Gyn/Onc Department	Orlando	Florida	United States	32804
4	Hematology-Onc. Assoc. of The Quad Cities	Bettendorf	Iowa	United States	52722
5	University of Iowa	Iowa City	Iowa	United States	52242
6	Franklin Square Hospital Center/MedStar Health-Section of Hematology/Oncology	Baltimore	Maryland	United States	21237-3998
7	Cancer Center at Hackensack	Hackensack	New Jersey	United States	07601
8	Columbia University College of Physicians and Surg	New York	New York	United States	10032
9	Hope: A Woman's Cancer Center	Asheville	North Carolina	United States	28816
10	University of North Carolina/ Division of Gyn Oncology	Chapel Hill	North Carolina	United States	27599-7570
11	Carolinas Medical Center/Gyn Oncology Department	Charlotte	North Carolina	United States	28232
12	Duke University/Division of Gynecologic Oncology	Durham	North Carolina	United States	27710-0001
13	Forsyth Regional Cancer Center	Winston-Salem	North Carolina	United States	27103
14	Gynecologic Oncology and Surgery	Oklahoma City	Oklahoma	United States	73112
15	PA Hematology/Oncology Associates	Philadelphia	Pennsylvania	United States	19106
16	Western Pennsylvania Hospital	Pittsburgh	Pennsylvania	United States	15224
17	MUSC-Div of Gyn/Oncology	Charleston	South Carolina	United States	29425
18	The West Cancer Clinic	Memphis	Tennessee	United States	38120
19	Southwest Regional Cancer Center	Austin	Texas	United States	78705

Sponsors and Collaborators

• Duke University
• Aventis Pharmaceuticals

Investigators

• Study Chair: Angeles A Secord, MD, Duke University

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Duke University
• ClinicalTrials.gov Identifier: NCT00090610
• Other Study ID Numbers: Pro00008381; DUKE UNIVERSITY MEDICAL CENTER; DUMC03
• First Posted: Aug 31, 2004
• Last Update Posted: Feb 25, 2015
• Last Verified: Dec 1, 2012

• Keywords provided by Duke University: Relapsed ovarian cancer
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial; Carboplatin; Docetaxel

Study Results

Participant Flow

Recruitment Details	Between January 2004 and March 2007, 150 participants were enrolled at this multicenter study.
Pre-assignment Detail	All patients were assigned

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
Period Title: Overall Study
STARTED	75	75
COMPLETED	74	74
NOT COMPLETED	1	1

Baseline Characteristics

Arm/Group Title	Arm 1	Arm 2	Total
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.	Total of all reporting groups
Overall Participants	75	75	150
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	63.8 (10.17)	64.9 (10.04)	63.9 (10.08)
Sex: Female, Male (Count of Participants)
Female	75 100%	75 100%	150 100%
Male	0 0%	0 0%	0 0%
Region of Enrollment (participants) [Number]
United States	75 100%	75 100%	150 100%

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival (PFS)
Description	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.
Time Frame	Every 6 months, to 18 months

Outcome Measure Data

Analysis Population Description

1 patient in each arm was excluded. The patient in Arm 1 did not complete 1 cycle of therapy. A patient in Arm 2 withdrew from the study

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
Measure Participants	74	74
Median (95% Confidence Interval) [months]	13.7	8.4

2. Secondary Outcome

Title	Objective Response Rate
Description	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
Time Frame	Every 6 months, starting at 12 months to 24 months

Outcome Measure Data

Analysis Population Description

Same as for PFS

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
Measure Participants	74	74
Number (95% Confidence Interval) [percentage of participants]	55.4 73.9%	43.3 57.7%

3. Secondary Outcome

Title	Quality of Life
Description	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.
Time Frame	Baseline performed 14 days before first dose, then every other cycle and at study termination

Outcome Measure Data

Analysis Population Description

The number of participants was based on QoL data available for Arm 1 and one patient withdrew on Arm 2.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
Measure Participants	74	74
Baseline	76.3 (14.0)	76.6 (16.1)
Cycle 1	65.1 (21.3)	73.3 (16.2)
Cycle 2	72.7 (15.1)	75.3 (13.6)
Cycle 3	69.4 (13.5)	75.6 (12.8)
Cycle 4	70.8 (15.07)	76.0 (13.7)
Cycle 5	69.3 (14.5)	74.0 (16.2)
Cycle 6	74.3 (10.6)	81.2 (9.7)
End of Study	71.4 (15.0)	78.0 (14.8)

4. Secondary Outcome

Title	Recurrence-Free Survival
Description	Recurrence-free survival is based on measurable disease using Kaplan-Meier estimates for the intent to treat (ITT) Population who achieved a complete response.
Time Frame	Every 6 months starting at 12 months, to 24 months

Outcome Measure Data

Analysis Population Description

Subjects who had a complete response.

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
Measure Participants	13	9
Median (95% Confidence Interval) [months]	20	15.8

5. Secondary Outcome

Title	Median Overall Survival
Time Frame	Every 6 months starting at 12 months, to 24 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Arm 1	Arm 2
Arm/Group Description	Docetaxel 30mg/m2 mg IV on Days 1 and 8, combined with carboplatin AUC 6 IV on Day 1, repeated every 21 days X 6 cycles or until disease progression	Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
Measure Participants	74	74
Median (95% Confidence Interval) [months]	33.2	30.1

Adverse Events

Time Frame	7-70 weeks
Adverse Event Reporting Description	Limited toxicity events including hematological, neurologic, hepatic, and renal toxicity were collected on the CRF. Other AEs were recorded in the patient's medical chart. The SAEs were captured from the first dose of study medication through 30 days after the last administration of study medication.
Arm/Group Title	Arm 1		Arm2
Arm/Group Description	Docetaxel 30 mg/m2 intravenously (IV) on Days 1 and 8, combined with carboplatin area under the concentration versus time curve (AUC) 6 IV on Day 1, repeated every 21 days for 6 cycles or until disease progression (DP) (whichever occurred first).		Docetaxel 30mg/m2 IV on Days 1 and 8, repeated every 21 days for 6 cycles until disease progression, followed by carboplatin AUC 6 IV every 21 days for 6 cycles or until disease progression.
All Cause Mortality
	Arm 1		Arm2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Arm 1		Arm2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/75 (21.3%)		18/74 (24.3%)
Blood and lymphatic system disorders
Deep Thrombophlebitis	1/75 (1.3%)	1	1/74 (1.4%)	1
Cardiac disorders
Pericardial Effusion	1/75 (1.3%)	1	0/74 (0%)	0
Heart Failure	0/75 (0%)	0	1/74 (1.4%)	1
Myocardial Infarct	0/75 (0%)	0	2/74 (2.7%)	2
Chest pain	3/75 (4%)	3	1/74 (1.4%)	1
Gastrointestinal disorders
Intestinal obstruction	1/75 (1.3%)	1	7/74 (9.5%)	7
diarrhea	1/75 (1.3%)	1	0/74 (0%)	0
tongue edema	0/75 (0%)	0	1/74 (1.4%)	1
vomiting	0/75 (0%)	0	1/74 (1.4%)	1
Colitis	1/75 (1.3%)	1	0/74 (0%)	0
Pancreatitis	1/75 (1.3%)	1	0/74 (0%)	0
GI perforation	1/75 (1.3%)	1	0/74 (0%)	0
GI disorder	1/75 (1.3%)	1	0/74 (0%)	0
Ileus	1/75 (1.3%)	1	0/74 (0%)	0
Immune system disorders
allergic reaction	1/75 (1.3%)	1	1/74 (1.4%)	1
Infections and infestations
Infection	1/75 (1.3%)	1	3/74 (4.1%)	3
Musculoskeletal and connective tissue disorders
Arthritis	1/75 (1.3%)	1	0/74 (0%)	0
Nervous system disorders
Cerebrovascular Accident	1/75 (1.3%)	1	0/74 (0%)	0
Other (Not Including Serious) Adverse Events
	Arm 1		Arm2
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	61/75 (81.3%)		61/74 (82.4%)
Blood and lymphatic system disorders
Hematologic toxicity	61/75 (81.3%)		61/74 (82.4%)
Hepatobiliary disorders
Hepatic	11/75 (14.7%)		13/74 (17.6%)
Nervous system disorders
Neurotoxicity	25/75 (33.3%)		31/74 (41.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.