Randomized Phase III Clinical Trial of Adjuvant Radiation Versus Chemoradiation in Intermediate Risk, Stage I/IIA Cervical Cancer Treated With Initial Radical Hysterectomy and Pelvic Lymphadenectomy (NCT #01101451)
Overview
- Phase
- Phase 3
- Intervention
- External Beam Radiation Therapy
- Conditions
- Cervical Adenocarcinoma
- Sponsor
- GOG Foundation
- Enrollment
- 340
- Locations
- 716
- Primary Endpoint
- Recurrence-free Survival (RFS) Rate at 3-years
- Status
- Completed
- Last Updated
- 11 months ago
Overview
Brief Summary
This randomized phase III trial studies radiation therapy with chemotherapy to see how well they work compared to radiation therapy alone in treating patients with stage I-IIA cervical cancer who previously underwent surgery. Radiation therapy uses high-energy x-rays to kill tumor cells. Drugs used in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. It is not yet known whether giving radiation therapy together with chemotherapy is more effective than radiation therapy alone in treating patients with cervical cancer.
Detailed Description
PRIMARY OBJECTIVE: I. To determine if post-operative adjuvant chemo-radiation therapy (CRT) can significantly improve recurrence-free survival (RFS) when compared to radiation therapy (RT) alone in stage I-IIA cervical cancer patients with intermediate-risk factors after treatment with radical hysterectomy. SECONDARY OBJECTIVES: I. To determine whether post-operative adjuvant CRT can improve overall survival (OS) when compared to RT alone in stage I-IIA cervical cancer patients with intermediate risk factors after treatment with radical hysterectomy. II. To assess differences (across treatment arms) in incidence and severity of therapy attributed adverse events utilizing the active version of Common Terminology Criteria for Adverse Events (CTCAE). III. To provide assessment of patient risk version (vs) benefit (positive study only). QUALITY OF LIFE OBJECTIVE: I. To determine whether post-operative adjuvant CRT improves the health-related quality-of-life (QOL) (compared to RT alone) as measured by Functional Assessment of Cancer Therapy-Cervix (FACT-Cx) Trial Outcome Index (TOI) and produce favorable toxicity profiles (with particular focus on treatment related genitourinary, gastrointestinal, neurological, pain and sexual adverse events). TRANSLATIONAL RESEARCH OBJECTIVES: I. To bank archival tumor tissue for research studies, including studies that evaluate the association between biomarkers, RFS, OS, and clinical-surgical-pathologic characteristics in patients randomized to post-operative adjuvant CRT compared to RT alone. II. To bank deoxyribonucleic acid (DNA) from whole blood for research studies, including studies that evaluate associations between single nucleotide polymorphisms (SNPs), and measures of clinical outcome, including RFS, OS, and adverse events in patients randomized to post-operative adjuvant CRT compared to RT alone. OUTLINE: Patients are randomized to 1 of 2 treatment arms. ARM I: Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks. ARM II: Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity. After completion of study therapy, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Pathologically proven primary cervical cancer I-IIA with squamous cell carcinoma, adenosquamous carcinoma or adenocarcinoma initially treated with a standard radical hysterectomy with pelvic lymphadenectomy
- •Patients with the following characteristics (depth of stromal invasion and lymphovascular space involvement to be pathologically confirmed):
- •Positive capillary-lymphovascular space involvement and one of the following:
- •Deep third penetration
- •Middle third penetration, clinical tumor \>= 2 cm
- •Superficial third penetration, clinical tumor \>= 5 cm
- •Negative capillary-lymphatic space involvement
- •Middle or deep third penetration, clinical tumor \>= 4 cm
- •Absolute neutrophil count (ANC) \>= 1,500/mcl
- •Platelets \>= 100,000/mcl
Exclusion Criteria
- •Patients with tumor in the parametria, pelvic lymph nodes or any other extra uterine site or with positive surgical margins
- •Patients with septicemia or severe infection
- •Patients with intestinal obstruction or gastrointestinal bleeding
- •Patients with postoperative fistula
- •Patients with cervix cancer who have received any previous radiation or chemotherapy
- •Patients whose circumstances do not permit completion of the study or the required follow-up
- •Patients with renal abnormalities requiring modification of radiation field (pelvic kidney, renal transplant, etc.)
- •Patients with GOG performance status of 3 or 4
- •Patients with a history of other invasive malignancies, with the exception of non-melanoma skin cancer, are excluded if there is any evidence of other malignancy being present within the last five years; patients are also excluded if their previous cancer treatment contraindicates this protocol therapy
Arms & Interventions
Arm I (EBRT, IMRT)
Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Intervention: External Beam Radiation Therapy
Arm I (EBRT, IMRT)
Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Intervention: Intensity-Modulated Radiation Therapy
Arm I (EBRT, IMRT)
Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Intervention: Laboratory Biomarker Analysis
Arm I (EBRT, IMRT)
Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Intervention: Quality-of-Life Assessment
Arm I (EBRT, IMRT)
Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Intervention: Questionnaire Administration
Arm II (cisplatin, EBRT, IMRT)
Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Cisplatin
Arm II (cisplatin, EBRT, IMRT)
Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: External Beam Radiation Therapy
Arm II (cisplatin, EBRT, IMRT)
Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Intensity-Modulated Radiation Therapy
Arm II (cisplatin, EBRT, IMRT)
Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Laboratory Biomarker Analysis
Arm II (cisplatin, EBRT, IMRT)
Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Quality-of-Life Assessment
Arm II (cisplatin, EBRT, IMRT)
Patients receive cisplatin IV over 1-2 hours on day 1 and undergo radiotherapy as in Arm I. Treatment with cisplatin repeats every 7 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Intervention: Questionnaire Administration
Outcomes
Primary Outcomes
Recurrence-free Survival (RFS) Rate at 3-years
Time Frame: 3 years from randomization
Estimate for probability of RFS at 3 years using Kaplan-Meier method, where RFS is defined as time from protocol registration (and randomization) to the date of first documented recurrence, death, or the date of last contact, whichever occurs first. Patients without recurrence or death were censored at the date of last contact.
Secondary Outcomes
- Overall Survival (OS) Rate at 3-years(3 years from randomization)
- Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period.(During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days.)
- Patient Risk-benefit(up to 11 years)
- Quality of Life (QOL) as Measured With the FACT-Cx TOI(1. Pre-treatment (baseline), 2. 3 weeks following the first day of treatment, 3. 7 weeks following the first day of treatment, 4. 36 weeks following the first day of treatment.)