Docetaxel in Treating Patients With Refractory or Recurrent Advanced Gynecologic Cancer

Study Overview
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Brief Summary
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RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Docetaxel may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving daily doses of docetaxel may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of docetaxel in treating patients with refractory or recurrent advanced gynecologic cancer.

Detailed Description
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OBJECTIVES: Primary Determine the maximum tolerated dose of metronomic docetaxel in patients with progressive or recurrent gynecologic cancer. Secondary Determine the response rate in patients treated with this drug. Determine the pharmacokinetics associated with this drug in these patients. OUTLINE: This is a dose-escalation study. Patients receive docetaxel intravenously (IV) over 1-2 minutes daily for up to 6 months in the absence of unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of docetaxel until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. After completion of study treatment, patients are followed every 3 months.

Official Title
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Phase I Study of Metronomic Daily Dosing of Docetaxel in Women With Progressive or Recurrent Gynecologic Cancer

Conditions
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Sarcoma, Cervical Cancer, Endometrial Cancer, Fallopian Tube Cancer, Ovarian Cancer, Peritoneal Cavity Cancer, Vaginal Cancer, Vulvar Cancer

Intervention / Treatment
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* Drug: docetaxel


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must have histologically confirmed advanced, refractory gynecologic cancer. Patients must have received prior chemotherapy, and must have residual or recurrent disease after initial therapy or after subsequent therapy. Patients must have at least one site of bi-dimensional measurable disease as defined in section 9 or must have evaluable but radiographically non-measurable disease associated with CA-125 > 50 units/ml on two measurements at least one week apart. Baseline measurements and CA-125 must be obtained for all patients within four weeks before registration. Patients must have Eastern Cooperative Oncology Group (ECOG) performance status 0-1. Patients must not have received any hormonal or immunologic therapy for 2 weeks or cytotoxic chemotherapy or radiation therapy for 4 weeks (nitrosoureas and mitomycin C require 6 weeks) prior to registration. Patients may not have a history of prior malignancy in the past 5 years other than non-melanoma skin cancer or in situ carcinoma of the cervix. Patients must have documented adequate organ function within 4 weeks of registration defined as: Marrow: WBC ≥ 3000/mm3, ANC ≥ 1500/mm3 , Hgb ≥ 8.0 g/dl, platelets ≥ 100,000/mm3 Hepatic: Total Bilirubin ≤ ULN, SGOT or SGPT and Alkaline Phosphatase must be within the range allowing for eligibility, as in the table below SGOT or SGPT: Meets 1 of the following criteria: Alkaline phosphatase (AP) normal AND SGOT or SGPT normal AP ≤ 5 times ULN AND SGOT or SGPT normal AP normal AND SGOT or SGPT ≤ 5 times ULN AP ≤ 2.5 ULN AND SGOT or SGPT ≤ 1.5 times ULN Renal: BUN ≤ 30 mg%, creatinine ≤ 1.5 mg% Age ≥ 18 years Exclusion Criteria: Pregnant or lactating. The agents used in this study may be teratogenic to a fetus and there is no information on the excretion of agents into breast milk. Patients of reproductive potential must use effective birth control, preferably with barrier methods. Prior history of myocardial infarction, congestive heart failure or significant ischemic or valvular heart disease. Patients with known brain metastases are not eligible. Peripheral neuropathy must be ≤ grade 2. Patients with a history of severe hypersensitivity reaction to docetaxel or other drugs formulated with polysorbate 80 must be excluded. Patient must given written informed consent indicating the investigational nature of the treatment and its potential risks

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
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Metronomic Docetaxel<br>Docetaxel will be administered by daily injection via pre-filled syringes into the patient's accessed subcutaneous port. | Drug: docetaxel<br>* Three patients will be enrolled and dosed at each level; from dose level 1 of 2.9 mg/m^2/day up to dose level 6 of 6.4 mg/m^2/day<br>* Other names: Taxotere;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum Tolerated Dose | Determine the maximum tolerated dose of metronomic docetaxel in patients with progressive or recurrent gynecologic cancer | Up to 180 Days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Response to Treatment | Determine the response rate in patients treated with this drug. | Up to 180 Days | 
| Pharmacokinetics | Determine the pharmacokinetics associated with this drug in these patients. | Day 1 through Day 5 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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recurrent ovarian germ cell tumor, recurrent cervical cancer, stage III cervical cancer, stage IVA cervical cancer, stage IVB cervical cancer, stage III endometrial carcinoma, recurrent endometrial carcinoma, stage IV endometrial carcinoma, fallopian tube cancer, stage III ovarian epithelial cancer, stage IV ovarian epithelial cancer, stage III ovarian germ cell tumor, stage IV ovarian germ cell tumor, recurrent ovarian epithelial cancer, recurrent uterine sarcoma, stage III uterine sarcoma, stage IV uterine sarcoma, stage III vaginal cancer, recurrent vaginal cancer, stage IVA vaginal cancer, stage IVB vaginal cancer, stage III vulvar cancer, recurrent vulvar cancer, stage IV vulvar cancer, ovarian sarcoma, ovarian stromal cancer, peritoneal cavity cancer