Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer

This study has been terminated.
Sponsor:
Collaborator:
Information provided by:
Gynecologic Oncology Group
ClinicalTrials.gov Identifier:
NCT00016341
First received: May 6, 2001
Last updated: April 10, 2013
Last verified: June 2007
  Purpose

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Estrogen can stimulate the growth of tumor cells. Hormone therapy using tamoxifen and megestrol may fight endometrial cancer by blocking the absorption of estrogen. It is not yet known whether chemotherapy is more effective than hormone therapy in treating endometrial cancer.

PURPOSE: Randomized phase III trial to compare the effectiveness of combination chemotherapy with that of hormone therapy in treating patients who have recurrent, stage III, or stage IV endometrial cancer.


Condition Intervention Phase
Endometrial Cancer
Biological: filgrastim
Drug: cisplatin
Drug: doxorubicin hydrochloride
Drug: megestrol acetate
Drug: paclitaxel
Drug: tamoxifen citrate
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Primary Purpose: Treatment
Official Title: Randomized Phase III Crossover Trial of Chemotherapy (Doxorubicin/Cisplatin/Paclitaxel and G-CSF) Versus Hormonal Therapy (Tamoxifen/Megestrol Acetate) in Patients With Stage III & IV or Recurrent Endometrial Cancer

Resource links provided by NLM:


Further study details as provided by Gynecologic Oncology Group:

Study Start Date: May 2001
Primary Completion Date: October 2003 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

  • Compare the progression-free survival and response of patients with stage III or IV or recurrent endometrial cancer treated with doxorubicin, cisplatin, paclitaxel, and filgrastim (G-CSF) vs tamoxifen and megestrol.
  • Compare the survival of patients treated with these regimens.
  • Determine if progesterone receptor status provides information on whether patients are more likely to benefit from chemotherapy.
  • Compare the toxicity profiles of these treatment regimens in these patients.
  • Compare the quality of life of patients treated with these regimens.

OUTLINE: This is a randomized, cross-over, multicenter study. Patients are stratified according to progesterone receptor status (negative vs positive). Patients are randomized to 1 of 2 treatment arms.

  • Arm I:Patients receive chemotherapy comprising doxorubicin IV over 15-30 minutes followed by cisplatin IV over 1 hour on day 1; paclitaxel IV over 3 hours on day 2; and filgrastim (G-CSF) subcutaneously beginning on day 3 and continuing for 10 days. Chemotherapy repeats every 21 days for up to 7 courses in the absence of disease progression or unacceptable toxicity.
  • At time of disease progression, patients cross-over to hormonal therapy as in arm II.
  • Arm II: Patients receive hormonal therapy comprising oral megestrol twice daily on weeks 1-3 followed by oral tamoxifen twice daily on weeks 4-6. Hormonal therapy repeats every 6 weeks in the absence of disease progression or unacceptable toxicity.

At time of disease progression, if patients have not previously been enrolled on arm I, patients cross-over to receive chemotherapy as in arm I.

Quality of life is assessed at baseline, 6 weeks, time of progression, and then after 6 weeks on cross-over therapy.

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

PROJECTED ACCRUAL: Approximately 630 patients will be accrued for this study within 42 months.

  Eligibility

Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed primary stage III or IV or recurrent endometrial cancer
  • Poor curative potential with radiotherapy or surgery (alone or in combination)
  • Measurable disease

    • At least one lesion accurately measured in at least one dimension

      • At least 20 mm by conventional techniques, including palpation, x-ray, CT scan, or MRI OR
      • At least 10 mm by spiral CT scan
    • Disease in a previously irradiated field as sole site of measurable disease allowed only if clear progression after completion of radiotherapy
  • Estrogen receptor(ER)/progesterone receptor (PR) status of primary tumor required

    • ER/PR status of measurable tumor optional

PATIENT CHARACTERISTICS:

Age:

  • Not specified

Performance status:

  • GOG 0-2

Life expectancy:

  • Not specified

Hematopoietic:

  • Platelet count at least 100,000/mm^3
  • Granulocyte count at least 1,500/mm^3

Hepatic:

  • Bilirubin normal
  • SGPT no greater than 3 times upper limit of normal

Renal:

  • Creatinine no greater than 1.6 mg/dL

Cardiovascular:

  • LVEF at least 50%
  • No third-degree or complete heart block, unless pacemaker is in place
  • Other conduction abnormalities or cardiac dysfunction allowed at the investigator's discretion
  • No history of deep venous thrombosis
  • No uncontrolled angina

Pulmonary:

  • No history of pulmonary embolus

Other:

  • No other malignancy within the past 5 years except nonmelanoma skin cancer
  • No concurrent medical illness that would preclude study
  • No serious uncontrolled infection
  • No serious peripheral neuropathy
  • No circumstances that would preclude study compliance
  • No sensitivity to E. coli-derived drug preparations

PRIOR CONCURRENT THERAPY:

Biologic therapy:

  • Prior biologic therapy allowed

Chemotherapy:

  • No prior cytotoxic chemotherapy, including chemotherapy for radiosensitization

Endocrine therapy:

  • No prior hormonal therapy for endometrial cancer

Radiotherapy:

  • See Disease Characteristics
  • At least 4 weeks since prior radiotherapy involving the whole pelvis or more than 50% of the spine

Surgery:

  • See Disease Characteristics

Other:

  • Concurrent cardiac conduction-altering medications such as digitalis, beta blockers, or calcium channel blockers allowed at the investigator's discretion
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00016341

  Show 50 Study Locations
Sponsors and Collaborators
Gynecologic Oncology Group
Investigators
Study Chair: Jeffrey D. Bloss, MD Washington University Siteman Cancer Center
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00016341     History of Changes
Other Study ID Numbers: CDR0000068624, GOG-0189
Study First Received: May 6, 2001
Last Updated: April 10, 2013
Health Authority: United States: Federal Government

Keywords provided by Gynecologic Oncology Group:
stage III endometrial carcinoma
stage IV endometrial carcinoma
recurrent endometrial carcinoma

Additional relevant MeSH terms:
Endometrial Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Paclitaxel
Liposomal doxorubicin
Cisplatin
Doxorubicin
Tamoxifen
Megestrol
Megestrol Acetate
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Radiation-Sensitizing Agents
Antibiotics, Antineoplastic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Estrogen Antagonists
Estrogen Receptor Modulators

ClinicalTrials.gov processed this record on September 18, 2014