Pelvic Radiation Therapy or Vaginal Implant Radiation Therapy, Paclitaxel, and Carboplatin in Treating Patients With High-Risk Stage I or Stage II Endometrial Cancer - Full Text View

Sponsor:	Gynecologic Oncology Group
Collaborator:	National Cancer Institute (NCI)
Information provided by:	National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:	NCT00807768

Purpose

RATIONALE: Radiation therapy uses high-energy x-rays to kill tumor cells. Implant radiation therapy uses radioactive material placed directly into or near a tumor to kill tumor cells. Drugs used in chemotherapy, such as paclitaxel and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. It is not yet known whether pelvic radiation therapy is more effective than vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with endometrial cancer.

PURPOSE: This randomized phase III trial is studying pelvic radiation therapy to see how well it works compared with vaginal implant radiation therapy, paclitaxel, and carboplatin in treating patients with high-risk stage I or stage II endometrial cancer.

Condition	Intervention	Phase
Endometrial Cancer Fatigue Neurotoxicity	Drug: carboplatin Drug: paclitaxel Radiation: brachytherapy Radiation: intensity-modulated radiation therapy Radiation: radiation therapy	Phase III

Study Type:	Interventional
Study Design:	Allocation: Randomized Primary Purpose: Treatment
Official Title:	A Phase III Trial of Pelvic Radiation Therapy Versus Vaginal Cuff Brachytherapy Followed By Paclitaxel/Carboplatin Chemotherapy in Patients With High Risk, Early Stage Endometrial Carcinoma

Resource links provided by NLM:

MedlinePlus related topics: Cancer Fatigue

Drug Information available for: Paclitaxel Carboplatin

U.S. FDA Resources

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

Primary Outcome Measures:

Duration of recurrence-free survival [ Designated as safety issue: No ]

Secondary Outcome Measures:

Duration of overall survival [ Designated as safety issue: No ]
Cumulative incidences of vaginal recurrence, pelvic recurrence, distant (extra-pelvic) recurrence, and death from endometrial cancer [ Designated as safety issue: No ]
Toxicity as assessed by NCI CTCAE v3.0 [ Designated as safety issue: Yes ]
Quality of life as assessed by the FACT-G Physical and Functional Well-Being, FACT-En, FACT/GOG-Ntx, FACIT-F, PROMIS Fatigue-SF1, and FACT-Cx questionnaires [ Designated as safety issue: No ]

Estimated Enrollment:	562
Study Start Date:	March 2009
Estimated Primary Completion Date:	March 2013 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: Arm I Patients undergo conventional or intensity-modulated pelvic radiotherapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.	Radiation: intensity-modulated radiation therapy Given for 5-6 weeks Radiation: radiation therapy Given for 5-6 weeks
Experimental: Arm II Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.	Drug: carboplatin Given IV Drug: paclitaxel Given IV Radiation: brachytherapy Given as 1-5 treatments

Arms

Assigned Interventions

Active Comparator: Arm I

Patients undergo conventional or intensity-modulated pelvic radiotherapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.

Radiation: intensity-modulated radiation therapy

Given for 5-6 weeks

Radiation: radiation therapy

Given for 5-6 weeks

Experimental: Arm II

Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Drug: carboplatin

Given IV

Drug: paclitaxel

Given IV

Radiation: brachytherapy

Given as 1-5 treatments

Detailed Description:

OBJECTIVES:

Primary

To compare the recurrence-free survival of patients with high-risk stage I or II endometrial carcinoma treated with pelvic radiotherapy vs vaginal cuff brachytherapy, paclitaxel, and carboplatin.

Secondary

To compare survival of patients treated with these regimens.
To compare patterns of failure in patients treated with these regimens.
To compare physical functioning, fatigue, and neurotoxicity in patients treated with these regimens.
To correlate primary comorbid illnesses and obesity with survival, fatigue, and physical functioning.
To evaluate the psychometric properties (e.g., construct validity, reliability, sensitivity to treatment, and responsiveness over time) of the PROMIS Fatigue-SF1.
To evaluate fatigue measurement equivalence between patients with endometrial cancer and age-matched women from the general population of the United States.

OUTLINE: This is a multicenter study. Patients are stratified according to extent of surgery (hysterectomy and bilateral salpingo-oophorectomy without lymph node sampling, lymph node dissection, or lymphadenectomy vs hysterectomy and bilateral salpingo-oophorectomy with lymph node sampling, lymph node dissection, or lymphadenectomy). Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology who are randomized to arm I are also stratified according to intent to use vaginal cuff brachytherapy (yes vs no). Patients are randomized to 1 of 2 treatment arms.

Arm I: Patients undergo conventional or intensity-modulated pelvic radiotherapy once daily, 5 days a week, for 5-6 weeks (total of 25-28 fractions) in the absence of disease progression or unacceptable toxicity. Patients with stage II disease or stage I disease with a confirmed diagnosis of clear cell and/or papillary serous histology may also undergo 1 or 2 intravaginal (i.e., vaginal cuff) brachytherapy boost treatments.
Arm II: Patients undergo vaginal cuff brachytherapy comprising 3-5 high-dose rate brachytherapy treatments over approximately 2 weeks or 1 or 2 low-dose rate brachytherapy treatments over 1-2 days. Beginning within 3 weeks after initiating brachytherapy, patients receive paclitaxel IV over 3 hours and carboplatin IV over 30-60 minutes on day 1. Chemotherapy repeats every 21 days for up to 3 courses in the absence of disease progression or unacceptable toxicity.

Patients complete questionnaires to assess quality of life, neurotoxicity, and fatigue at baseline, 4 weeks, 10-11 weeks, 8 months, and 14 months.

After completion of study therapy, patients are followed periodically for up to 10 years.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Female
Accepts Healthy Volunteers:	No

Criteria

DISEASE CHARACTERISTICS:

Diagnosis of endometrial carcinoma, meeting 1 of the following criteria:
- Stage I disease with high-intermediate risk factors with positive or negative cytology (e.g., grade 2 or 3 tumor, presence of lymphovascular space invasion, and/or outer half myometrial invasion), meeting 1 of the following criteria:
  - Age ≥ 70 years with 1 risk factor
  - Age ≥ 50 years with 2 risk factors
  - Age ≥ 18 years with 3 risk factors
- Stage II (occult or gross involvement) disease (any histology) with or without risk factors
  - Occult disease is defined as lesions that are identified as an incidental finding after hysterectomy in the absence of gross cervical disease
- Stage I-II disease with serous or clear cell histology with or without other risk factors allowed provided the disease is uterine-confined (with or without cervical stromal invasion or endocervical glandular involvement), and with peritoneal cytology negative for malignancy
Has undergone hysterectomy and bilateral salpingo-oophorectomy (laparotomy or laparoscopic approach, including robot-assisted) with or without pelvic and para-aortic lymphadenectomy within the past 4-12 weeks
- If nodal dissection was not performed, pelvic and para-aortic nodes must be clinically negative with no evidence of distant disease by post-operative, pre-treatment CT scan/MRI
  - Suspicious nodes that have been biopsied (re-staging surgery, fine-needle aspiration) allowed provided they are pathologically negative
- No pathologically confirmed spread of disease to pelvic or para-aortic lymph nodes or adnexal structures, and/or other anatomic sites, or serous or clear cell histology and positive cytologic washings
No recurrent disease
No surgical or clinical stage III or IV endometrial carcinoma
No sarcoma, carcinosarcoma (i.e., malignant mixed mullerian tumor), or non-epithelial uterine malignancies (i.e., leiomyosarcoma of the uterine corpus)

PATIENT CHARACTERISTICS:

GOG performance status 0-2
ANC ≥ 1,500/mcl
Platelet count ≥ 100,000/mcl
Serum creatinine normal OR creatinine clearance > 50 mL/min
Bilirubin ≤ 1.5 times upper limit of normal (ULN)
SGOT ≤ 2.5 times ULN
Alkaline phosphatase ≤ 2.5 times ULN
No neuropathy (sensory or motor) > grade 1
No other invasive malignancy within the past 5 years except non-melanoma skin cancer
No contraindications to pelvic radiotherapy (e.g., pelvic kidney, connective tissue disease, or inflammatory bowel disease)

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
No prior non-surgical therapy for endometrial cancer, including chemotherapy, radiotherapy (e.g., pre-operative or post-operative brachytherapy), hormonal therapy, or biological therapy
No prior systemic chemotherapy or radiotherapy for another malignancy
No concurrent whole-abdominal, extended-field, or interstitial radiotherapy
No concurrent erythropoietin therapy
Concurrent enrollment on GOG-0210 (molecular marker study) allowed

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00807768

Show 412 Study Locations

Sponsors and Collaborators

Gynecologic Oncology Group

National Cancer Institute (NCI)

Investigators

Study Chair:	D. Scott McMeekin, MD	Oklahoma University Cancer Institute
Investigator:	Marcus E. Randall, MD	Lucille P. Markey Cancer Center at University of Kentucky

More Information

Additional Information:

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

Featured trial article This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Philip J. DiSaia, Gynecologic Oncology Group
ClinicalTrials.gov Identifier:	NCT00807768 History of Changes
Other Study ID Numbers:	CDR0000629591, GOG-0249
Study First Received:	December 11, 2008
Last Updated:	February 3, 2012
Health Authority:	Unspecified

Keywords provided by National Cancer Institute (NCI):

fatigue
neurotoxicity
endometrial clear cell carcinoma
endometrial papillary serous carcinoma
endometrial adenoacanthoma

endometrial adenocarcinoma
endometrial adenosquamous cell carcinoma
stage IA endometrial carcinoma
stage IB endometrial carcinoma
stage II endometrial carcinoma

Additional relevant MeSH terms:

Endometrial Neoplasms
Sarcoma, Endometrial Stromal
Fatigue
Neurotoxicity Syndromes
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Uterine Diseases
Genital Diseases, Female
Neoplasms, Complex and Mixed
Neoplasms by Histologic Type
Sarcoma
Neoplasms, Connective and Soft Tissue

Endometrial Stromal Tumors
Signs and Symptoms
Nervous System Diseases
Poisoning
Substance-Related Disorders
Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on February 09, 2012