Weekly Paclitaxel/Carboplatin With Neupogen in Gynaecological Cancers

Study Overview
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Brief Summary
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Rationale: The administration of prophylactic G-CSF may reduce the toxicity of a weekly paclitaxel/carboplatin regimen in gynaecological cancers. Purpose: This multicenter phase II trial is studying the side effects of weekly paclitaxel/carboplatin when given with prophylactic G-SCF in patients with recurrent epithelial ovarian-, primary peritoneal or fallopian tube cancers, endometrial carcinoma or cervical carcinoma. Data obtained in this trial will be compared with historical data as published earlier. The trial will include 3 cohorts of 36 patients: Subjects with ovarian, fallopian tube or peritoneal carcinoma Subjects with endometrial cancer Subjects with cervical carcinoma Treatment: Subjects will receive Paclitaxel 60 mg/m² followed by Carboplatin AUC 2.7 intravenously weekly during 18 weeks. Filgrastim (Neupogen) will be given to all patients on day 5 and possibly on day 6 of each course. Subjects will be evaluated by CT/MRI scan after 9 cycles of chemotherapy (week 10), after 18 cycles of chemotherapy, then every 6 months for the next 2 years and then if clinically indicated. Subjects who develop disease progression will discontinue therapy. Subjects who have no evidence of disease progression after completion of study therapy will be followed until disease progression, withdrawal of informed consent, or death.

Detailed Description
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Primary objective: - To evaluate the occurrence of grade 4 neutropenia during weekly paclitaxel/carboplatin with prophylactic G-CSF Secondary objectives: To evaluate per cohort the occurrence of grade 4 neutropenia To evaluate other toxicities To evaluate the dose reductions or dose delays in the chemotherapy To determine the progression free survival according to RECIST v1.1 To evaluate the response rate and overall survival

Official Title
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Phase II Study of Weekly Paclitaxel/Carboplatin in Combination With Prophylactic G-CSF in the Treatment of Gynaecological Cancers

Conditions
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Ovarian Cancer, Endometrial Cancer, Uterine Cervical Cancer

Intervention / Treatment
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* Drug: Filgrastim
* Drug: Paclitaxel
* Drug: Carboplatin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: All cohorts: Female subjects more than 18 years of age Performance status must be ECOG 0-2. Adequate organ function Measurable disease by RECIST version 1.1 or CA125 progression according to the GCIG definition (Vergote et al). Written informed consent Ovarian, fallopian tube or peritoneal carcinoma cohort: Histologically confirmed diagnosis of invasive epithelial ovarian,fallopian tube, or peritoneal carcinoma (serous, mucinous, endometrioid,clear cell, or carcinosarcomas are eligible). Patients should have received at least 1 earlier platin treatment but should be platin refractory (progression within 28 days after the last dose of platin) or platin resistant (progression within 6 months after last dose of platin therapy). Earlier weekly or dose-dense regimens with paclitaxel and carboplatin are not allowed. Consolidation after the last platin dose with non-platinum containing chemotherapy or molecular targeted drugs is allowed Endometrial carcinoma cohort Histologically confirmed diagnosis of endometrial carcinoma (endometrioid,adenoacanthoma, adenosquamous, serous, clear cell carcinoma or carcinosarcomas are eligible). Recurrent or advanced endometrial carcinoma can be included. Earlier platin therapy is allowed. But earlier weekly or dose-dense regimens with paclitaxel and carboplatin are not allowed. Cervical carcinoma cohort Histologically confirmed diagnosis of cervical carcinoma (adenocarcinoma or squamous carcinomas are eligible). Recurrent or advanced endometrial carcinoma can be included. Earlier platin (including concomitant with radiotherapy) therapy is allowed. But earlier weekly or dose-dense regimens with paclitaxel and carboplatin are not allowed. Exclusion Criteria: Other histologies than those mentioned above such as non-epithelial ovarian carcinomas, neuro-endocrine tumors, sarcomas, metastases from other primary tumors, ... Earlier weekly or dose-dense paclitaxel and carboplatin regimen. Any unstable or serious condition e.g. uncontrolled infection requiring systemic therapy. Prior other malignancies treated primarily or for recurrence within 3 years prior to inclusion in this study, except for completely resected non- melanomatous skin carcinoma or successfully treated in situ carcinoma of the skin or cervix of the uterus. Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures Metastatic disease to the brain or leptomeninges. Treatment with any of the following anti-cancer therapies: radiation therapy, surgery or tumor embolization within 14 days prior to the first dose of study chemotherapy. chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of study drug Known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs similar or related to Paclitaxel, Carboplatin or G-CSF.

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: Prevention
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Filgrastim<br> | Drug: Filgrastim<br>* All subjects will receive standard treatment with paclitaxel followed by carboplatin intravenously during 18 weeks. Filgrastim (Neupogen) will be given prophylactically on day 5. An additional dose will be given on day 6 in case of severe neutropenia during the course of the trial.<br>Drug: Paclitaxel<br>* All subjects will receive standard treatment with paclitaxel followed by carboplatin intravenously during 18 weeks. Filgrastim (Neupogen) will be given prophylactically on day 5. An additional dose will be given on day 6 in case of severe neutropenia during the course of the trial.<br>Drug: Carboplatin<br>* All subjects will receive standard treatment with paclitaxel followed by carboplatin intravenously during 18 weeks. Filgrastim (Neupogen) will be given prophylactically on day 5. An additional dose will be given on day 6 in case of severe neutropenia during the course of the trial.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurrence of grade 4 neutropenia |  | 2.5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Occurence of other toxicities |  | 2.5 years | 
| Occurence of dose reductions and dose delays |  | 2.5 years | 
| Progression free survival |  | 3 years, 7 years | 
| Overall survival |  | 3 years, 7 years | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Ovarian Cancer, Endometrial Cancer, Endometrial Carcinoma, Uterine Cervical Cancer, Paclitaxel, Carboplatin, Neupogen, Filgrastim, Ovarian Diseases, Peritoneal Diseases, Fallopian Tube Diseases, Endocrine System Diseases, Endometrial Diseases, Uterine Cervical Diseases, Neoplasms, Neoplasms, Glandular and Epithelial, Ovarian Neoplasms, Peritoneal Neoplasms, Fallopian Tube Neoplasms, Neoplasms, Endometrial, Cervical Neoplasms, Genital Neoplasms, Female, Urogenital Neoplasms, Antineoplastic Agents, Phytogenic, Genital Diseases, Female