Ovarian Cancer
Conditions
Brief summary
In this study the investigators will be using an AUC of 6 based on creatinine clearance using the Carboplatin dosing formula used for Gynecologic Oncology Group protocols. Given that myelosuppression was significant using the docetaxel dose of 75 mg/m\*2 in the SCOTROC trial, the prophylactic use of pegylated G-CSF in this Phase II trial is warranted. The expectation would be that patients will be able to receive their cycles in a more timely fashion, with less delays, thereby allowing for improved outcomes and decreased hospitalizations due to myelosuppression.
Interventions
Sponsors
Sanofi
Washington University School of Medicine
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Histologically confirmed newly diagnosed Stage III/IV epithelial ovarian or primary peritoneal carcinoma at time of initial diagnosis * Treatment must start within 8 weeks of surgery * Subjects may be measurable per RECIST criteria or evaluable for disease response by CA125. Evaluable CA 125 levels are defined as an elevated CA125 pre operatively which either remains elevated post-operatively or normalizes after surgery * No prior chemotherapy or radiation therapy * Age ≥ 18 * Performance Status must be ≤ 2 (ECOG) * Peripheral neuropathy: must be ≤ grade 1 * Hematologic (minimal values) * Absolute neutrophil count ≥ 1,500/mm3 * Hemoglobin ≥ 8.0 g/dl * Platelet count ≥ 100,000/mm3 * Hepatic \*Total Bilirubin ≤ ULN * AST and ALT and Alkaline Phosphatase must be within the range allowing for eligibility. * If alkaline phosphatase is ≤ ULN and AST or ALT is \>5x ULN then the patient is not eligible * If alkaline phosphatase is \>1x but ≤2.5 x the ULN and the AST or ALT is \>1.5x the ULN then the patient is not eligible * If alkaline phosphatase is \>2.5x but ≤5x the ULN and the AST or ALT is \>1x the ULN then the patient is not eligible * If alkaline phosphatase is \>5x the ULN then the patient is not eligible * Renal: Creatinine (serum) less than or equal to 1.5 ULN, CTC grade 1. * Women of childbearing potential must have a negative pregnancy test and must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter. PT/PTT ≤ 1.5 x's ULN
Exclusion criteria
* Patients with a history of severe hypersensitivity reaction to Docetaxel or other drugs formulated with polysorbate 80. * Women who are pregnant or breast-feeding. * Patients who have signs of infection or who have not recovered from the effects of recent surgery * Patients with a performance status of 3 or 4 * Patients with a second malignancy within past 5 years other than non-melanoma skin carcinoma. * Patients who have received prior myelosuppressive chemotherapy or XRT.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3 | Through 30 days after completion of treatment (approximately 22 weeks) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Efficacy of Regimen as Measured by CA-125 Response | Completion of treatment (approximately 18 weeks) | * Progression is defined as one of the following: * Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 ≥ twice the upper limit of normal on two occasions at least one week apart * Patients with elevated CA-125 pretreatment which never normalizes must show evidence of CA-125 ≥ 2 times the nadir value OR \> 50% increase from the nadir on two occasions at least one week apart, * Patients with CA-125 in the normal range pretreatment must show evidence of CA-125 ≥ two times the upper limit of normal on two occasions at least one week apart. * Complete response is defined as a CA-125 value \<13 confirmed on two occasions at least 2 weeks apart. * Partial Response is defined as a reduction of at least 50% from the original elevated CA-125 value (original value must have been \> 50), confirmed on two occasions at least 2 weeks apart. * Stable Disease is defined as not meeting one of the above criteria. |
| Time to Progression (TTP) | Completion of follow-up | Progressive disease is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Unequivocal progression of existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin, in the opinion of the treating physician within 8 weeks of study entry is also considered increasing disease (in this circumstance an explanation must be provided). In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% increase in the LD is required. |
| Progression-free Survival (PFS) | Completion of follow-up | -Progression-Free Survival is the period from study entry until disease progression, death or date of last contact. |
| Quality of Life (QoL) as Measured by FACT-O Assessment Tool | Completion of follow-up | * The FACT-O questionnaire consists of a Physical Well-Being Section, Social/Family Well-Being Section, Emotional Well-Being Section, Functional Well-Being Section, and Additional Concerns Section * Answers range from Not at all to Very Much with 0 = not at all and 4 = very much |
| Overall Survival (OS) | Completion of follow-up | Overall Survival is the observed length of life from entry into the study to death or the date of last contact |
Other
| Measure | Time frame |
|---|---|
| Adverse Events as Measured by Number of Events Experienced by All Participants | 30 days after completion of treatment (approximately 22 weeks) |
Countries
United States
Participant flow
Recruitment details
The study opened to participant enrollment on 01/12/2006 and closed to participant enrollment on 12/01/2009.
Participants by arm
| Arm | Count |
|---|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) * Docetaxel intravenously over 1 hour followed by carboplatin intravenously over 30 minutes-1 hour on day 1 every 21 days for maximum of 6 cycles
* Pegylated G-CSF on day 2 every 21 days for maximum of 6 cycles | 18 |
| Total | 18 |
Baseline characteristics
| Characteristic | Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) |
|---|---|
| Age, Continuous | 62 years |
| Region of Enrollment United States | 18 participants |
| Sex: Female, Male Female | 18 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 0 / 0 |
| serious Total, serious adverse events | 0 / 0 |
Outcome results
Primary
Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3
Time frame: Through 30 days after completion of treatment (approximately 22 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3 | Grade 3 neutropenia | 4 participants |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Incidence of Grade 3-4 Neutropenia as Measured by CTCAE Version 3 | Grade 4 neutropenia | 0 participants |
Secondary
Efficacy of Regimen as Measured by CA-125 Response
* Progression is defined as one of the following: * Patients with elevated CA-125 pretreatment and normalization of CA-125 must show evidence of CA-125 ≥ twice the upper limit of normal on two occasions at least one week apart * Patients with elevated CA-125 pretreatment which never normalizes must show evidence of CA-125 ≥ 2 times the nadir value OR \> 50% increase from the nadir on two occasions at least one week apart, * Patients with CA-125 in the normal range pretreatment must show evidence of CA-125 ≥ two times the upper limit of normal on two occasions at least one week apart. * Complete response is defined as a CA-125 value \<13 confirmed on two occasions at least 2 weeks apart. * Partial Response is defined as a reduction of at least 50% from the original elevated CA-125 value (original value must have been \> 50), confirmed on two occasions at least 2 weeks apart. * Stable Disease is defined as not meeting one of the above criteria.
Time frame: Completion of treatment (approximately 18 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Efficacy of Regimen as Measured by CA-125 Response | Complete response | 16 participants |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Efficacy of Regimen as Measured by CA-125 Response | Partial response | 1 participants |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Efficacy of Regimen as Measured by CA-125 Response | Stable disease | 0 participants |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Efficacy of Regimen as Measured by CA-125 Response | Progressive disease | 1 participants |
Secondary
Overall Survival (OS)
Overall Survival is the observed length of life from entry into the study to death or the date of last contact
Time frame: Completion of follow-up
Population: The sponsor withdrew funding for the study which meant there was no funding for completion of accrual, follow-up or statistical analysis.
Secondary
Progression-free Survival (PFS)
-Progression-Free Survival is the period from study entry until disease progression, death or date of last contact.
Time frame: Completion of follow-up
Population: The sponsor withdrew funding for the study which meant there was no funding for completion of accrual, follow-up or statistical analysis.
Secondary
Quality of Life (QoL) as Measured by FACT-O Assessment Tool
* The FACT-O questionnaire consists of a Physical Well-Being Section, Social/Family Well-Being Section, Emotional Well-Being Section, Functional Well-Being Section, and Additional Concerns Section * Answers range from Not at all to Very Much with 0 = not at all and 4 = very much
Time frame: Completion of follow-up
Population: The sponsor withdrew funding for the study which meant there was no funding for completion of accrual, follow-up or statistical analysis.
Secondary
Time to Progression (TTP)
Progressive disease is at least a 20% increase in the sum of LD of target lesions taking as references the smallest sum LD or the appearance of new lesions within 8 weeks of study entry. Unequivocal progression of existing non-target lesions, other than pleural effusions without cytological proof of neoplastic origin, in the opinion of the treating physician within 8 weeks of study entry is also considered increasing disease (in this circumstance an explanation must be provided). In the case where the ONLY target lesion is a solitary pelvic mass measured by physical exam, which is not radiographically measurable, a 50% increase in the LD is required.
Time frame: Completion of follow-up
Population: The sponsor withdrew funding for the study which meant there was no funding for completion of accrual, follow-up or statistical analysis.
Other Pre-specified
Adverse Events as Measured by Number of Events Experienced by All Participants
Time frame: 30 days after completion of treatment (approximately 22 weeks)
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Low white blood cell count | 25 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Low absolute neutrophil count | 21 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Low platelet count | 47 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Low hemoglobin | 78 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Allergy/immunology | 3 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Cardiovascular | 4 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Coagulation | 1 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Constitutional symptoms | 42 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Dermatology | 64 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Endocrine | 56 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Gastrointestinal | 43 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Genitourinary/renal | 1 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Hemorrhage | 2 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Infection/febrile neutropenia | 9 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Lymphatics | 2 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Metabolic/laboratory | 74 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Musculoskeletal | 6 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Neurologic | 30 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Ocular/visual | 2 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Pain | 27 events |
| Arm 1: (Docetaxel, Carboplatin, Pegylated G-CSF) | Adverse Events as Measured by Number of Events Experienced by All Participants | Pulmonary | 2 events |