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