Docetaxel in Treating Patients With Refractory or Recurrent Advanced Gynecologic Cancer

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

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.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Cervical Cancer; Ovarian Cancer; Fallopian Tube Cancer; Peritoneal Cavity Cancer; Vulvar Cancer; Endometrial Cancer; Vaginal Cancer
• Intervention / Treatment: Drug: docetaxel

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 18
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metronomic Docetaxel; Docetaxel will be administered by daily injection via pre-filled syringes into the patient's accessed subcutaneous port.	Drug: docetaxel; 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; Other Names: Taxotere

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Masonic Cancer Center, University of Minnesota

Study record dates

Study Major Dates

• Study Start: March 1, 2004
• Primary Completion (Actual): December 1, 2008
• Study Completion (Actual): December 1, 2008

Study Registration Dates

• First Submitted: February 6, 2006
• First Submitted That Met QC Criteria: February 6, 2006
• First Posted (Estimate): February 7, 2006

Study Record Updates

• Last Update Posted (Actual): November 29, 2017
• Last Update Submitted That Met QC Criteria: November 27, 2017
• Last Verified: November 1, 2017

More Information

Terms related to this study

• Keywords: stage III ovarian epithelial cancer; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; fallopian tube cancer; stage IV endometrial carcinoma; recurrent endometrial carcinoma; stage III cervical cancer; stage IVA cervical cancer; stage IV uterine sarcoma; recurrent uterine sarcoma; ovarian sarcoma; recurrent cervical cancer; stage IVB cervical cancer; stage III uterine sarcoma; ovarian stromal cancer; recurrent ovarian germ cell tumor; stage III ovarian germ cell tumor; stage IV ovarian germ cell tumor; stage III endometrial carcinoma; recurrent vaginal cancer; stage III vaginal cancer; stage IVA vaginal cancer; stage IVB vaginal cancer; recurrent vulvar cancer; stage III vulvar cancer; stage IV vulvar cancer; peritoneal cavity cancer
• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Cervical Diseases; Uterine Diseases; Adnexal Diseases; Fallopian Tube Diseases; Vaginal Diseases; Vulvar Diseases; Sarcoma; Uterine Cervical Neoplasms; Fallopian Tube Neoplasms; Endometrial Neoplasms; Vulvar Neoplasms; Vaginal Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: 2003LS034; UMN-WCC-35 (Other Identifier: Women's Cancer Center, University of Minnesota); 0307M50626 (Other Identifier: IRB, University of Minnesota)