Carboplatin Plus Docetaxel With Day 2 Pegylated G-CSF (Neulasta®) in Patients With Advanced Stage Ovarian Carcinoma

Study Overview
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Brief Summary
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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.

Official Title
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Phase II Trial of Carboplatin Plus Docetaxel With Day 2 Pegylated G-CSF (Neulasta®) in the Front-line Treatment of Patients With Advanced Stage Ovarian Carcinoma

Conditions
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Ovarian Cancer

Intervention / Treatment
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* Drug: Docetaxel
* Drug: Carboplatin
* Drug: Pegylated G-CSF


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Arm 1: (docetaxel, carboplatin, pegylated G-CSF)<br>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 | Drug: Docetaxel<br> <br> * Other names: Taxotere®;Drug: Carboplatin<br> <br> * Other names: CBDCA;Drug: Pegylated G-CSF<br> <br> * Other names: Pegfilgrastim;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. | Completion of treatment (approximately 18 weeks) | 
| 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. | Completion of follow-up | 
| Overall Survival (OS) | Overall Survival is the observed length of life from entry into the study to death or the date of last contact | Completion of follow-up | 
| Progression-free Survival (PFS) | -Progression-Free Survival is the period from study entry until disease progression, death or date of last contact. | Completion of follow-up | 
| 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 | Completion of follow-up |