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

PRIMARY OBJECTIVES:

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).

IV. 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).

TERTIARY 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