Ovarian Cancer
Conditions
Keywords
Relapsed ovarian cancer
Brief summary
The purpose of this study is to compare the progression-free survival of two treatment regimens for relapsed ovarian cancer.
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.
Interventions
DRUGDocetaxel
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
DRUGCarboplatin
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
Sponsors
Aventis Pharmaceuticals
Duke University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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 |
| 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. |
| 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. |
| Median Overall Survival | Every 6 months starting at 12 months, to 24 months | — |
Countries
United States
Participant flow
Recruitment details
Between January 2004 and March 2007, 150 participants were enrolled at this multicenter study.
Pre-assignment details
All patients were assigned
Participants by arm
| Arm | Count |
|---|---|
| Arm 1 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 | 75 |
| Arm 2 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. | 75 |
| Total | 150 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Arm 1 | Arm 2 | Total |
|---|---|---|---|
| Age, Continuous | 63.8 years STANDARD_DEVIATION 10.17 | 64.9 years STANDARD_DEVIATION 10.04 | 63.9 years STANDARD_DEVIATION 10.08 |
| Region of Enrollment United States | 75 participants | 75 participants | 150 participants |
| Sex: Female, Male Female | 75 Participants | 75 Participants | 150 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 61 / 75 | 61 / 74 |
| serious Total, serious adverse events | 16 / 75 | 18 / 74 |
Outcome results
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.
Time frame: Every 6 months, to 18 months
Population: 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 | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 | Progression-free Survival (PFS) | 13.7 months |
| Arm 2 | Progression-free Survival (PFS) | 8.4 months |
Secondary
Median Overall Survival
Time frame: Every 6 months starting at 12 months, to 24 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 | Median Overall Survival | 33.2 months |
| Arm 2 | Median Overall Survival | 30.1 months |
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
Time frame: Every 6 months, starting at 12 months to 24 months
Population: Same as for PFS
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm 1 | Objective Response Rate | 55.4 percentage of participants |
| Arm 2 | Objective Response Rate | 43.3 percentage of participants |
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.
Time frame: Baseline performed 14 days before first dose, then every other cycle and at study termination
Population: The number of participants was based on QoL data available for Arm 1 and one patient withdrew on Arm 2.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm 1 | Quality of Life | Baseline | 76.3 units on a scale | Standard Deviation 14 |
| Arm 1 | Quality of Life | Cycle 5 | 69.3 units on a scale | Standard Deviation 14.5 |
| Arm 1 | Quality of Life | Cycle 1 | 65.1 units on a scale | Standard Deviation 21.3 |
| Arm 1 | Quality of Life | Cycle 2 | 72.7 units on a scale | Standard Deviation 15.1 |
| Arm 1 | Quality of Life | Cycle 3 | 69.4 units on a scale | Standard Deviation 13.5 |
| Arm 1 | Quality of Life | Cycle 4 | 70.8 units on a scale | Standard Deviation 15.07 |
| Arm 1 | Quality of Life | Cycle 6 | 74.3 units on a scale | Standard Deviation 10.6 |
| Arm 1 | Quality of Life | End of Study | 71.4 units on a scale | Standard Deviation 15 |
| Arm 2 | Quality of Life | End of Study | 78.0 units on a scale | Standard Deviation 14.8 |
| Arm 2 | Quality of Life | Baseline | 76.6 units on a scale | Standard Deviation 16.1 |
| Arm 2 | Quality of Life | Cycle 3 | 75.6 units on a scale | Standard Deviation 12.8 |
| Arm 2 | Quality of Life | Cycle 5 | 74.0 units on a scale | Standard Deviation 16.2 |
| Arm 2 | Quality of Life | Cycle 6 | 81.2 units on a scale | Standard Deviation 9.7 |
| Arm 2 | Quality of Life | Cycle 1 | 73.3 units on a scale | Standard Deviation 16.2 |
| Arm 2 | Quality of Life | Cycle 4 | 76.0 units on a scale | Standard Deviation 13.7 |
| Arm 2 | Quality of Life | Cycle 2 | 75.3 units on a scale | Standard Deviation 13.6 |
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.
Time frame: Every 6 months starting at 12 months, to 24 months
Population: Subjects who had a complete response.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Arm 1 | Recurrence-Free Survival | 20 months |
| Arm 2 | Recurrence-Free Survival | 15.8 months |