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

Phase 3
Completed
Conditions
Endometrial Serous Adenocarcinoma
Stage III Uterine Corpus Cancer
Endometrial Adenosquamous Carcinoma
Endometrial Adenocarcinoma
Endometrial Clear Cell Adenocarcinoma
Endometrial Endometrioid Adenocarcinoma, Variant With Squamous Differentiation
Interventions
Biological: Filgrastim
Biological: Pegfilgrastim
Registration Number
NCT00006011
Lead Sponsor
Gynecologic Oncology Group
Brief Summary

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.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
659
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

Exclusion Criteria

Not provided

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)CisplatinPatients 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.
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)PegfilgrastimPatients 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.
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)FilgrastimPatients 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.
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)PegfilgrastimPatients 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.
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)FilgrastimPatients 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.
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)PaclitaxelPatients 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.
Arm I (doxorubicin, cisplatin, filgrastim, pegfilgrastim)Doxorubicin HydrochloridePatients 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.
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)Doxorubicin HydrochloridePatients 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.
Arm II (doxorubicin, cisplatin, paclitaxel, filgrastim)CisplatinPatients 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.
Primary Outcome Measures
NameTimeMethod
Recurrence-Free Survival of Eligible Patients Who Received a Random Treatment Allocation.study entry up to 5 years post treatment

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.

Secondary Outcome Measures
NameTimeMethod

Trial Locations

Locations (1)

Gynecologic Oncology Group

🇺🇸

Philadelphia, Pennsylvania, United States

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