Radiation Therapy With or Without Chemotherapy in Patients With Stage I or Stage II Cervical Cancer Who Previously Underwent Surgery
- Clements University Hospital
David Miller, M.D.
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
This randomized phase III trial studies radiation therapy with chemotherapy to see how well it works compared to radiation therapy alone in treating patients with stage I or stage II 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 or by stopping them from dividing. 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.
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.
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 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).
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.
- 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 times normal
- Alkaline phosphate = 3 times normal
- Serum glutamic oxaloacetic transaminase (SGOT) ? 3 times 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
- 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