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Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer
This study has been completed.
Sponsors and Collaborators: Gynecologic Oncology Group
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00016341
  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
Drug: cisplatin
Drug: doxorubicin hydrochloride
Drug: filgrastim
Drug: megestrol acetate
Drug: paclitaxel
Drug: tamoxifen citrate
Phase III

MedlinePlus related topics: Cancer
Drug Information available for: Doxorubicin Doxorubicin hydrochloride Megestrol acetate Megestrol Filgrastim Cisplatin Paclitaxel Granulocyte colony-stimulating factor Tamoxifen Tamoxifen citrate Citric acid Sodium Citrate
U.S. FDA Resources
Study Type: Interventional
Study Design: Treatment, Randomized, Active Control
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

Further study details as provided by National Cancer Institute (NCI):

Study Start Date: May 2001
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
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 Siteman Cancer Center at Barnes-Jewish Hospital - Saint Louis
  More Information

Clinical trial summary from the National Cancer Institute's PDQ® database  This link exits the ClinicalTrials.gov site

Study ID Numbers: CDR0000068624, GOG-0189
Study First Received: May 6, 2001
Last Updated: July 23, 2008
ClinicalTrials.gov Identifier: NCT00016341  
Health Authority: United States: Federal Government

Keywords provided by National Cancer Institute (NCI):
stage III endometrial carcinoma
stage IV endometrial carcinoma
recurrent endometrial carcinoma

Study placed in the following topic categories:
Citric Acid
Genital Neoplasms, Female
Uterine Diseases
Urogenital Neoplasms
Tamoxifen
Megestrol
Recurrence
Doxorubicin
Carcinoma
Genital Diseases, Female
Endometrial Neoplasms
Cisplatin
Paclitaxel
Uterine Neoplasms
Endometrial cancer
Megestrol Acetate

Additional relevant MeSH terms:
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Contraceptive Agents
Hormone Antagonists
Physiological Effects of Drugs
Contraceptives, Oral
Contraceptive Agents, Female
Hormones, Hormone Substitutes, and Hormone Antagonists
Bone Density Conservation Agents
Reproductive Control Agents
Antibiotics, Antineoplastic
Selective Estrogen Receptor Modulators
Estrogen Receptor Modulators
Neoplasms by Site
Therapeutic Uses
Contraceptives, Oral, Synthetic
Appetite Stimulants
Estrogen Antagonists
Antineoplastic Agents, Hormonal
Mitosis Modulators
Central Nervous System Stimulants
Antimitotic Agents
Pharmacologic Actions
Neoplasms
Radiation-Sensitizing Agents
Tubulin Modulators
Antineoplastic Agents, Phytogenic
Central Nervous System Agents

ClinicalTrials.gov processed this record on January 16, 2009