Cervical Adenocarcinoma, Cervical Adenosquamous Carcinoma, Cervical Squamous Cell Carcinoma, Not Otherwise Specified, Stage IA Cervical Cancer AJCC v6 and v7, Stage IB Cervical Cancer AJCC v6 and v7, Stage I Cervical Cancer AJCC v6 and v7, Stage IIA Cervical Cancer AJCC v7
Conditions
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.
Interventions
DRUGCisplatin
Given IV
RADIATIONExternal Beam Radiation Therapy
Undergo radiotherapy
RADIATIONIntensity-Modulated Radiation Therapy
Undergo radiotherapy
OTHERLaboratory Biomarker Analysis
Correlative studies
OTHERQuality-of-Life Assessment
Ancillary studies
OTHERQuestionnaire Administration
Ancillary studies
Sponsors
National Cancer Institute (NCI)
GOG Foundation
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| 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. |
| 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. |
Other
| Measure | Time frame | Description |
|---|---|---|
| Local Control | Up to 11 years | Assessed with Exact Logistic Regression adjusted known prognostic factors. |
| Site(s) of Recurrence | Up to 11 years | The site(s) of first disease recurrence will be classified as: pelvic-only, extra-pelvic-only or pelvic-and-extra-pelvic and tabulated by treatment group. The test of the hypothesis that the probability of local failure is independent of randomized treatment will be assessed with exact logistic regression adjusted know prognostic factors. |
| Treatment Compliance | Up to 11 years | Assessed by the number of cycles and amount of chemoradiotherapy administered, treatment span, incidence and duration of treatment delays, reason for delays, and reason why off study therapy. |
Countries
Japan, South Korea, United States
Participant flow
Recruitment details
GOG-0263 opened to accrual on April 12, 2010, and closed to accrual on April 11, 2022.
Participants by arm
| Arm | Count |
|---|---|
| Arm I (Radiation) Patients undergo pelvic external-beam radiation therapy (EBRT) or intensity-modulated radiation therapy (IMRT) 5 days a week for 5.5 weeks. | 158 |
| Arm II (Cisplatin + Radiation) 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. | 158 |
| Total | 316 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Eligible and never treated | 0 | 5 |
| Overall Study | Ineligible and never treated | 2 | 2 |
| Overall Study | Ineligible and treated | 12 | 8 |
Baseline characteristics
| Characteristic | Arm I (Radiation) | Arm II (Cisplatin + Radiation) | Total |
|---|---|---|---|
| Age, Customized 20-29 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Customized 30-39 years | 28 Participants | 47 Participants | 75 Participants |
| Age, Customized 40-49 years | 62 Participants | 53 Participants | 115 Participants |
| Age, Customized 50-59 years | 46 Participants | 33 Participants | 79 Participants |
| Age, Customized 60-69 years | 13 Participants | 17 Participants | 30 Participants |
| Age, Customized 70-79 years | 5 Participants | 6 Participants | 11 Participants |
| Age, Customized >= 80 years | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 12 Participants | 15 Participants | 27 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 142 Participants | 142 Participants | 284 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 4 Participants | 1 Participants | 5 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 2 Participants | 2 Participants | 4 Participants |
| Race (NIH/OMB) Asian | 79 Participants | 87 Participants | 166 Participants |
| Race (NIH/OMB) Black or African American | 12 Participants | 5 Participants | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 1 Participants | 0 Participants | 1 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 2 Participants | 6 Participants | 8 Participants |
| Race (NIH/OMB) White | 62 Participants | 58 Participants | 120 Participants |
| Sex: Female, Male Female | 158 Participants | 158 Participants | 316 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 20 / 158 | 12 / 158 |
| other Total, other adverse events | 140 / 170 | 158 / 161 |
| serious Total, serious adverse events | 7 / 170 | 9 / 161 |
Outcome results
Primary
Recurrence-free Survival (RFS) Rate at 3-years
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.
Time frame: 3 years from randomization
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Radiation) | Recurrence-free Survival (RFS) Rate at 3-years | 85.4 percentage of participants |
| Arm II (Cisplatin + Radiation) | Recurrence-free Survival (RFS) Rate at 3-years | 88.5 percentage of participants |
p-value: 0.092795% CI: [0.408, 1.192]Log Rank
Secondary
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period.
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Time frame: During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days.
Population: Randomized participants who received any assigned protocol therapy
| Arm | Measure | Group | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|---|
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Other blood/lymphatics | 0 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Metabolism/nutrition | 0 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Other investigations | 7 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Musculoskeletal/connective tissue | 1 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Platelet count decreased | 0 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Nervous system | 2 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Gastrointestinal | 10 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Psychiatric | 1 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | White blood cell decreased | 3 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Renal/urinary | 2 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | General and administration site | 2 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Reproductive/breast | 2 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Neutrophil count decreased | 2 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Skin/subcutaneous | 0 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Infections/infestations | 4 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Vascular disorders | 0 Participants |
| Arm I (Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Anemia | 1 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Vascular disorders | 1 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Anemia | 6 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Other blood/lymphatics | 4 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | White blood cell decreased | 45 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Platelet count decreased | 4 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Neutrophil count decreased | 27 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Other investigations | 8 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Gastrointestinal | 12 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | General and administration site | 3 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Infections/infestations | 4 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Metabolism/nutrition | 7 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Musculoskeletal/connective tissue | 0 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Nervous system | 1 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Psychiatric | 1 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Renal/urinary | 2 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Reproductive/breast | 1 Participants |
| Arm II (Cisplatin + Radiation) | Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period. | Skin/subcutaneous | 3 Participants |
Secondary
Overall Survival (OS) Rate at 3-years
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.
Time frame: 3 years from randomization
Population: Eligible participants
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Arm I (Radiation) | Overall Survival (OS) Rate at 3-years | 90.3 percentage of participants |
| Arm II (Cisplatin + Radiation) | Overall Survival (OS) Rate at 3-years | 97.2 percentage of participants |
95% CI: [0.286, 1.199]
Secondary
Patient Risk-benefit
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.
Time frame: up to 11 years
Population: Per protocol, patient risk-benefit will be assessed only for a positive study. Based on the results information at the specified significance level, patient risk-benefit was not assessed as pre-specified
Secondary
Quality of Life (QOL) as Measured With the FACT-Cx TOI
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.
Time frame: 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.
Population: Eligible patients who completed baseline and at lease one follow-up QOL assessments.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Arm I (Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | Baseline | 83.5 units on a scale | Standard Deviation 15.4 |
| Arm I (Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | 3 weeks | 79.0 units on a scale | Standard Deviation 16.4 |
| Arm I (Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | 7 weeks | 80.1 units on a scale | Standard Deviation 17 |
| Arm I (Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | 36 weeks | 88.8 units on a scale | Standard Deviation 15.5 |
| Arm II (Cisplatin + Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | 36 weeks | 88.1 units on a scale | Standard Deviation 12.3 |
| Arm II (Cisplatin + Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | Baseline | 80.1 units on a scale | Standard Deviation 15.4 |
| Arm II (Cisplatin + Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | 7 weeks | 71.8 units on a scale | Standard Deviation 17.1 |
| Arm II (Cisplatin + Radiation) | Quality of Life (QOL) as Measured With the FACT-Cx TOI | 3 weeks | 71.4 units on a scale | Standard Deviation 15.3 |
Other Pre-specified
Local Control
Assessed with Exact Logistic Regression adjusted known prognostic factors.
Time frame: Up to 11 years
Other Pre-specified
Site(s) of Recurrence
The site(s) of first disease recurrence will be classified as: pelvic-only, extra-pelvic-only or pelvic-and-extra-pelvic and tabulated by treatment group. The test of the hypothesis that the probability of local failure is independent of randomized treatment will be assessed with exact logistic regression adjusted know prognostic factors.
Time frame: Up to 11 years
Other Pre-specified
Treatment Compliance
Assessed by the number of cycles and amount of chemoradiotherapy administered, treatment span, incidence and duration of treatment delays, reason for delays, and reason why off study therapy.
Time frame: Up to 11 years