Comparison of Two Combination Chemotherapy Regimens Plus Radiation Therapy in Treating Patients With Stage III or Stage IV Endometrial Cancer

A Randomized Phase III Study of Tumor Volume Directed Pelvic Plus or Minus Para-Aortic Irradiation Followed by Cisplatin and Doxorubicin or Cisplatin, Doxorubicin and Paclitaxel for Advanced Endometrial Carcinoma

Randomized phase III trial to compare the effectiveness of two combination chemotherapy regimens plus radiation therapy in treating patients who have stage III or stage IV endometrial cancer. Radiation therapy uses high-energy x-rays to damage tumor cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one chemotherapy drug with radiation therapy may kill more tumor cells. It is not yet known which combination chemotherapy regimen plus radiation therapy is more effective for endometrial cancer.

Study Overview

• Status: Completed
• Conditions: Stage III Uterine Corpus Cancer; Endometrial Clear Cell Adenocarcinoma; Endometrial Serous Adenocarcinoma; Endometrial Adenocarcinoma; Endometrial Adenosquamous Carcinoma; Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation
• Intervention / Treatment: Drug: Cisplatin; Drug: Paclitaxel; Drug: Doxorubicin Hydrochloride; Biological: Pegfilgrastim; Biological: Filgrastim

Detailed Description

OBJECTIVES:

I. Compare survival and progression-free survival in patients with stage III endometrial carcinoma treated with tumor volume-directed pelvic radiotherapy with or without paraaortic radiotherapy followed by cisplatin and doxorubicin with or without paclitaxel.

II. Compare short and long-term toxic effects of these treatment regimens in this patient population.

OUTLINE: This is a randomized, multicenter study. Patients are stratified according to radiotherapy field (pelvic vs extended field). Within 8 weeks after surgery, patients receive tumor volume-directed pelvic radiotherapy with or without paraaortic nodal radiotherapy once daily for 5 consecutive days for up to 16 weeks after surgery. Within 8 weeks of completing radiotherapy, patients are randomized to 1 of 2 chemotherapy treatment arms.

Arm I: Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) subcutaneously (SC) or pegfilgrastim on days 2-11.

Arm II: Patients receive doxorubicin and cisplatin as in arm I, paclitaxel IV over 3 hours on day 2, and G-CSF SC or pegfilgrastim on days 3-12. Treatment repeats every 3 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.

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

PROJECTED ACCRUAL: A total of 614 patients (307 per treatment arm) will be accrued for this study within 5.2 years.

• Study Type: Interventional
• Enrollment (Actual): 659
• Phase: Phase 3

Contacts and Locations

Study Locations

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

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Child; Adult; Older Adult
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

Description

Inclusion Criteria:

• Histologically confirmed advanced endometrial carcinoma with any histology, including:

  • Clear cell and serous papillary carcinoma

• Surgical stage III disease, including:

  • Positive adnexa
  • Tumor invading the serosa
  • Positive pelvic and/or paraaortic nodes
  • Involvement of bowel mucosa
  • Intraabdominal metastases
  • Positive pelvic washings
  • Vaginal involvement within the radiation port

• Must have had prior surgery, including hysterectomy and bilateral salpingo-oophorectomy

  • Tumor maximally debulked to a maximum residual diameter of no greater than 2 cm

  • Paraaortic lymph node sampling allowed

    • If positive, must have negative chest CT scan
• No recurrent disease
• No parenchymal liver metastases
• No disease outside the abdomen
• Performance status - GOG 0-2
• At least 3 months
• Absolute neutrophil count at least 1,500/mm^3
• Platelet count at least 100,000/mm^3
• Bilirubin no greater than 1.5 times normal
• SGOT/SGPT no greater than 3 times normal
• Alkaline phosphatase no greater than 3 times normal
• Creatinine no greater than 1.6 mg/dL
• LVEF at least 50% within 6 months of study entry
• No other prior or concurrent malignancy within the past 5 years except adequately treated nonmelanoma skin cancer
• No serious comorbid illness that would preclude study participation
• No prior chemotherapy
• See Disease Characteristics
• No prior pelvic or abdominal radiotherapy
• No prior radiotherapy for prior malignancy
• See Disease Characteristics

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim); Patients receive doxorubicin IV over 30 minutes immediately followed by cisplatin IV over 1 hour on day 1. Patients also receive filgrastim (G-CSF) SC or pegfilgrastim on days 2-11.	Drug: Cisplatin; Given IV; Drug: Doxorubicin Hydrochloride; Given IV; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; Neulasta; GCSF-SD01; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Nivestim
Experimental: Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim); Patients receive doxorubicin and cisplatin as in arm I, paclitaxel IV over 3 hours on day 2, and G-CSF SC or pegfilgrastim on days 3-12. Treatment repeats every 3 weeks for a maximum of 6 courses in the absence of disease progression or unacceptable toxicity.	Drug: Cisplatin; Given IV; Drug: Paclitaxel; Given IV; Other Names: Anzatax; TAX; Drug: Doxorubicin Hydrochloride; Given IV; Biological: Pegfilgrastim; Given SC; Other Names: Filgrastim SD-01; Neulasta; GCSF-SD01; Biological: Filgrastim; Given SC; Other Names: G-CSF; r-metHuG-CSF; Nivestim

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation.	Recurrence is defined as discovery of disease not previously present by clinical, radiographic, and/or laboratory means or as a 50% or greater increase in the product of two perpendicular diameters from any documented lesion. Recurrence-free survival is defined as time in months the patient is alive, recurrence-free starting from the date of randomization. Intention to treat among eligible participants who receive random treatment allocation.	study entry up to 5 years post treatment

Collaborators and Investigators

• Sponsor: Gynecologic Oncology Group
• Collaborators: National Cancer Institute (NCI); Eastern Cooperative Oncology Group
• Investigators: Principal Investigator: Howard Homesley, Gynecologic Oncology Group

Study record dates

Study Major Dates

• Study Start: July 1, 2000
• Primary Completion (Actual): March 1, 2010

Study Registration Dates

• First Submitted: July 5, 2000
• First Submitted That Met QC Criteria: January 26, 2003
• First Posted (Estimate): January 27, 2003

Study Record Updates

• Last Update Posted (Estimate): May 19, 2015
• Last Update Submitted That Met QC Criteria: April 30, 2015
• Last Verified: April 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Uterine Neoplasms; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Neoplasms, Complex and Mixed; Cystadenocarcinoma; Neoplasms, Cystic, Mucinous, and Serous; Ovarian Neoplasms; Endometrial Neoplasms; Carcinoma; Adenocarcinoma; Cystadenocarcinoma, Serous; Carcinoma, Endometrioid; Adenocarcinoma, Clear Cell; Carcinoma, Adenosquamous; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Immunologic Factors; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antineoplastic Agents, Phytogenic; Topoisomerase II Inhibitors; Topoisomerase Inhibitors; Adjuvants, Immunologic; Antibiotics, Antineoplastic; Paclitaxel; Lenograstim; Doxorubicin; Liposomal doxorubicin
• Other Study ID Numbers: GOG-0184 (Other Identifier: CTEP); U10CA027469 (U.S. NIH Grant/Contract); NCI-2012-02350 (Registry Identifier: CTRP (Clinical Trial Reporting Program)); ECOG-G0184; RTOG-EN0130; CDR0000068020