Radiation Therapy With or Without Chemotherapy in Patients With Stage I-IIA Cervical Cancer Who Previously Underwent Surgery

Phase 3

Completed

• Conditions: Stage IA Cervical Cancer AJCC v6 and v7; Cervical Adenocarcinoma; Stage IIA Cervical Cancer AJCC v7; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer AJCC v6 and v7; Stage I Cervical Cancer AJCC v6 and v7
• Interventions: Radiation: External Beam Radiation Therapy; Drug: Cisplatin; Radiation: Intensity-Modulated Radiation Therapy; Other: Quality-of-Life Assessment; Other: Laboratory Biomarker Analysis; Other: Questionnaire Administration

• Registration Number: NCT01101451
• Lead Sponsor: GOG Foundation

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.

Study Timeline

• Study First Submitted: 2010-04-09
• Study First Submitted QC: 2010-04-09
• Study Start: 2010-04-12
• Study First Posted: 2010-04-12
• Primary Completion: 2024-01-15
• Study Completion: 2024-04-02
• Status Verified: 2024-10
• Results First Submitted: 2024-10-28
• Results First Submitted QC: 2025-04-15
• Results First Posted: 2025-05-01
• Last Update Submitted: 2025-05-21
• Last Update Posted: 2025-05-23

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 340

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

• Creatinine =< upper limit of normal (ULN) or calculated creatinine clearance >= 60 mL/min

• Bilirubin =< 1.5 x normal

• Alkaline phosphate =< 3 x normal

• Serum glutamic oxaloacetic transaminase (SGOT) =< 3 x normal

• Gynecologic Oncology Group (GOG) performance status 0, 1, 2

• Patients should not be randomized less than 3 weeks post-surgery but will not be acceptable for randomization more than 8 weeks post-surgery

• Patients who have met the pre-entry requirements

• Patients must have signed an approved informed consent and authorization permitting release of personal health information

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm I (EBRT, IMRT)	External Beam Radiation Therapy	Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Arm I (EBRT, IMRT)	Questionnaire Administration	Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Arm I (EBRT, IMRT)	Intensity-Modulated Radiation Therapy	Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Arm II (cisplatin, EBRT, IMRT)	Questionnaire Administration	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.
Arm I (EBRT, IMRT)	Quality-of-Life Assessment	Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Arm II (cisplatin, EBRT, IMRT)	Laboratory Biomarker Analysis	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.
Arm I (EBRT, IMRT)	Laboratory Biomarker Analysis	Patients undergo pelvic EBRT or IMRT once daily, 5 days a week, for 5.5 weeks.
Arm II (cisplatin, EBRT, IMRT)	External Beam Radiation Therapy	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.
Arm II (cisplatin, EBRT, IMRT)	Intensity-Modulated Radiation Therapy	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.
Arm II (cisplatin, EBRT, IMRT)	Quality-of-Life Assessment	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.
Arm II (cisplatin, EBRT, IMRT)	Cisplatin	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.

Primary Outcome Measures

Name	Time	Method
Recurrence-free Survival (RFS) Rate at 3-years	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 Outcome Measures

Name	Time	Method
Overall Survival (OS) Rate at 3-years	3 years from randomization	Estimate for probability of overall survival at 3 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.
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.	Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Patient Risk-benefit	up to 11 years	The reporting group (2) did not demonstrate improved RFS compared to the reporting group (1) at the pre-specified significance level. Per the protocol, patient risk-benefit will be assessed only for a positive study.; This is not assessed due to non-positive study per the protocol.
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.	The patient-reported QOL is assessed with the Trial Outcome Index of the Functional Assessment of Cancer Therapy-Cervix (FACT-Cx TOI). The FACT-Cx TOI is ranged 0-116 and a larger FACT-Cx TOI score suggests a favorable QoL.

Trial Locations

Locations (716)

Anchorage Associates in Radiation Medicine; 🇺🇸 Anchorage, Alaska, United States

Anchorage Radiation Therapy Center; 🇺🇸 Anchorage, Alaska, United States

Alaska Breast Care and Surgery LLC; 🇺🇸 Anchorage, Alaska, United States

Alaska Oncology and Hematology LLC; 🇺🇸 Anchorage, Alaska, United States

Alaska Regional Hospital; 🇺🇸 Anchorage, Alaska, United States

Alaska Women's Cancer Care; 🇺🇸 Anchorage, Alaska, United States

Anchorage Oncology Centre; 🇺🇸 Anchorage, Alaska, United States

Katmai Oncology Group; 🇺🇸 Anchorage, Alaska, United States

Providence Alaska Medical Center; 🇺🇸 Anchorage, Alaska, United States

Fairbanks Memorial Hospital; 🇺🇸 Fairbanks, Alaska, United States

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