Brief Title
Combination Chemotherapy Compared With Hormone Therapy in Treating Patients With Recurrent, Stage III, or Stage IV Endometrial Cancer
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
Brief Summary
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.
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.
Study Phase
Phase 3
Study Type
Interventional
Condition
Endometrial Cancer
Intervention
filgrastim
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Biological
Start Date
May 2001
Primary Completion Date
October 2003
Eligibility 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
Gender
Female
Ages
N/A - N/A
Accepts Healthy Volunteers
No
Contacts
Jeffrey D. Bloss, MD, ,
Location Countries
Canada
Location Countries
Canada
Administrative Informations
NCT ID
NCT00016341
Organization ID
CDR0000068624
Secondary IDs
GOG-0189
Study Sponsor
Gynecologic Oncology Group
Collaborators
National Cancer Institute (NCI)
Study Sponsor
Jeffrey D. Bloss, MD, Study Chair, Washington University Siteman Cancer Center
Verification Date
June 2007