Combination Chemotherapy Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

Phase I Trial of the Treatment of Advanced Endometrial Cancer With Concurrent Weekly Paclitaxel and Cisplatin and Whole Abdominal Radiation Therapy

This phase I trial is studying the side effects and best dose of combination chemotherapy when given with radiation therapy in treating patients with stage III or stage IV endometrial cancer. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Radiation therapy uses high-energy x-rays to damage tumor cells.

Study Overview

• Status: Completed
• Conditions: Stage III Uterine Corpus Cancer; Stage IV Uterine Corpus Cancer; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma
• Intervention / Treatment: Drug: Cisplatin; Drug: Paclitaxel; Radiation: Radiation Therapy

Detailed Description

OBJECTIVES:

I. Determine the safety and maximum tolerated doses of paclitaxel and cisplatin when administered with radiotherapy in patients with stage III or IV endometrial cancer.

II. Assess the time to disease progression and overall survival of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of paclitaxel and cisplatin.

Patients receive paclitaxel IV over 1 hour and cisplatin IV on days 1, 8, 15, 22, 29, and 36. Patients also undergo whole abdominal radiotherapy for 5 consecutive days weekly for 6 weeks.

Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin 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. Once the MTD is determined, additional patients are treated at that dose level.

Patients are followed every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.

PROJECTED ACCRUAL: A total of 3-48 patients will be accrued for part I and 14-20 patients will be accrued for part II of this study.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19103
      • Gynecologic Oncology Group

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:

• Histologically confirmed surgical stage III or IV endometrial cancer
• Any stage clear or serous papillary endometrial cancer
• Positive para-aortic lymph nodes allowed

• Tumor must be surgically reduced to 2 cm or less within 8 weeks of study

  • Must have had hysterectomy and bilateral salpingo-oophorectomy
• No recurrent disease
• No metastases to lung or liver parenchyma or inguinal or scalene lymph nodes
• Performance status - GOG 0-2
• Absolute neutrophil count greater than 2,000/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times upper limit of normal (ULN)
• SGOT no greater than 3 times ULN
• Creatinine no greater than 1.5 times ULN
• No other prior or concurrent malignancy in the past 5 years except non-melanoma skin cancer
• No prior chemotherapy
• No prior radiotherapy
• See Disease Characteristics
• No more than 8 weeks since prior surgery
• No prior anticancer therapy that would preclude study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Treatment (paclitaxel, cisplatin, abdominal radiotherapy); Patients receive paclitaxel IV over 1 hour and cisplatin IV on days 1, 8, 15, 22, 29, and 36. Patients also undergo whole abdominal radiotherapy for 5 consecutive days weekly for 6 weeks. Cohorts of 3-6 patients receive escalating doses of paclitaxel and cisplatin until the 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. Once the MTD is determined, additional patients are treated at that dose level.

Drug: Cisplatin; Given IV; Drug: Paclitaxel; Given IV; Other Names: Anzatax; TAX; Radiation: Radiation Therapy; Undergo whole abdominal radiation therapy; Other Names: Cancer Radiotherapy; Irradiate; Irradiated; Irradiation; RT

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Acute toxicity for identification of MTD, using the 21 major categories of the Cancer Therapy Evaluation Program Common Toxicity Criteria (CTEP CTC) v2.0	Calculated using a 90% conditional likelihood-based confidence bound.	Up to 30 days post-radiotherapy
Chronic toxicity based on the NCI CTC Radiation Therapy Oncology Group (RTOG)/European Organization for Research and Treatment of Cancer (EORTC) late radiation morbidity scoring scheme		Up to 6 months post-radiotherapy

Secondary Outcome Measures

Outcome Measure	Time Frame
Site (local/distant) of treatment failure	Up to 5 years
Number of dose level combinations that will have been evaluated prior to MTD establishment	Up to 60 months

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI)
• Investigators: Principal Investigator: D. McMeekin, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): July 1, 2009

Study Registration Dates

• First Submitted: June 2, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): December 31, 2014
• Last Update Submitted That Met QC Criteria: December 29, 2014
• Last Verified: December 1, 2014

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Uterine Diseases; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Adenocarcinoma; Endometrial Neoplasms; Cystadenocarcinoma, Serous; Adenocarcinoma, Clear Cell; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Paclitaxel; Cisplatin
• Other Study ID Numbers: GOG-9907 (Other Identifier: CTEP); U10CA027469 (U.S. NIH Grant/Contract); NCI-2012-02334 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); CDR0000067856