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.
Brief Title
Radiation Therapy With or Without Chemotherapy in Patients With Stage I-IIA Cervical Cancer Who Previously Underwent Surgery
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.
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.
Categories
Completion Date
Completion Date Type
Actual
Conditions
Cervical Adenocarcinoma
Cervical Adenosquamous Carcinoma
Cervical Squamous Cell Carcinoma, Not Otherwise Specified
Stage I Cervical Cancer AJCC v6 and v7
Stage IA Cervical Cancer AJCC v6 and v7
Stage IB Cervical Cancer AJCC v6 and v7
Stage IIA Cervical Cancer AJCC v7
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
* 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
* 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
Inclusion 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
* 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
* 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
Gender
Female
Gender Based
false
Healthy Volunteers
No
Last Update Post Date
Last Update Post Date Type
Actual
Last Update Submit Date
Minimum Age
18 Years
NCT Id
NCT01101451
Org Class
Network
Org Full Name
GOG Foundation
Org Study Id
GOG-0263
Overall Status
Completed
Phases
Phase 3
Primary Completion Date
Primary Completion Date Type
Actual
Official Title
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)
Primary Outcomes
Outcome Description
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.
Outcome Measure
Recurrence-free Survival (RFS) Rate at 3-years
Outcome Time Frame
3 years from randomization
Secondary Ids
Secondary Id
NCI-2011-02037
Secondary Id
GOG-0263
Secondary Id
GOG-0263
Secondary Outcomes
Outcome Description
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.
Outcome Time Frame
3 years from randomization
Outcome Measure
Overall Survival (OS) Rate at 3-years
Outcome Description
Number of participants with a maximum grade of 3 or higher during treatment period. Adverse events are graded and categorized using CTCAE v4.0.
Outcome Time Frame
During treatment period and up to 21 days after stopping the study treatment. The median treatment duration was 39 days.
Outcome Measure
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period.
Outcome Description
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.
This is not assessed due to non-positive study per the protocol.
Outcome Time Frame
up to 11 years
Outcome Measure
Patient Risk-benefit
Outcome Description
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.
Outcome 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.
Outcome Measure
Quality of Life (QOL) as Measured With the FACT-Cx TOI
Start Date
Start Date Type
Actual
Status Verified Date
First Post Date
First Post Date Type
Estimated
First Submit Date
First Submit QC Date
Std Ages
Adult
Older Adult
Maximum Age Number (converted to Years and rounded down)
999
Minimum Age Number (converted to Years and rounded down)
18
Investigators
Investigator Type
Principal Investigator
Investigator Name
David Smotkin
Investigator Email
dsmotkin@montefiore.org
Investigator Phone
718-920-5157
Categories Mesh Debug
Prostate Cancer --- UROGENITAL NEOPLASMS
Cancer --- NEOPLASMS BY SITE
Cancer --- NEOPLASMS
Gynecologic Cancers --- UTERINE CERVICAL DISEASES
Gynecologic Cancers --- UTERINE DISEASES
MeSH Terms
UTERINE CERVICAL NEOPLASMS
UTERINE NEOPLASMS
GENITAL NEOPLASMS, FEMALE
UROGENITAL NEOPLASMS
NEOPLASMS BY SITE
NEOPLASMS
UTERINE CERVICAL DISEASES
UTERINE DISEASES
GENITAL DISEASES, FEMALE
FEMALE UROGENITAL DISEASES
FEMALE UROGENITAL DISEASES AND PREGNANCY COMPLICATIONS
UROGENITAL DISEASES
GENITAL DISEASES
CISPLATIN
1,2-DIAMINOCYCLOHEXANEPLATINUM II CITRATE
PLATINUM
RADIATION
RADIOTHERAPY, INTENSITY-MODULATED
CHLORINE COMPOUNDS
INORGANIC CHEMICALS
NITROGEN COMPOUNDS
PLATINUM COMPOUNDS
METALS, HEAVY
ELEMENTS
TRANSITION ELEMENTS
METALS
PHYSICAL PHENOMENA
RADIOTHERAPY, CONFORMAL
RADIOTHERAPY, COMPUTER-ASSISTED
RADIOTHERAPY
THERAPEUTICS