GOG 0724: Phase III Randomized Study of Concurrent Chemotherapy and Pelvic Radiation Therapy with or without Adjuvant Chemotherapy in High-Risk Patients with Early-stage Cervical Carcinoma Following Radical Hysterectomy
This is a Phase 3, randomized, multicenter study. Patients are stratified according to planned use of brachytherapy (no vs yes), radiotherapy modality (standard external beam radiotherapy [eBRT] vs intensity-modulated radiotherapy [iMRT]), and radiotherapy dose (45 Gy vs 50.4 Gy). Patients are randomized to 1 of 2 treatment arms.
* arm i: Patients undergo standard eBRT or iMRT to the pelvis once daily 5 days a week for 5-6 weeks. Patients also receive concurrent cisplatin iV over 1 hour once weekly for 6 weeks.
noTe: Some patients may also undergo brachytherapy beginning within 7 days after completion of radiotherapy.
* arm ii: Patients receive chemoradiotherapy as in arm i. Beginning 4-6 weeks after completion of chemoradiotherapy, patients receive paclitaxel iV over 3 hours and carboplatin iV over 30 minutes on day 1. Treatment repeats every 21 days for 4 courses in the absence of disease progression or unacceptable toxicity.
Quality of life is assessed by the FaCT-GoG/nTX4, FaCT-Cx, and FaCiT-D questionnaires at baseline; at the completion of chemoradiotherapy then at 6, 12, and 24 months after completion of chemoradiotherapy.
Blood and tissue samples may be collected for gene expression analysis by iHC and for biomarker and polymorphism studies for each subject.
after completion of study treatment, patients are followed up every 3 months for 2 years, every 6 months for 3 years, and then annually thereafter.
1.Patients must have undergone radical hysterectomy (open, laparoscopically or robotic) and staging including both para-aortic and pelvic node sampling for cervical carcinoma within 70 days prior to study entry.
2.Patients have histologic proof of squamouns, adenocarcinoma or adenosquamous carcinoma of the cervix.
3. FIGO Stage IA2, Ib or IIA
4. Patient must have any/all of the following high-risk features post surgery: positive pelvic
nodes; positive parametrium; or positive para-aortic nodes-completely resected and PET/CT
negative (required if + PA nodes during surgery)
5. Zubrod performance status 0-1.
6. Patient had a history and physical within 56 days of study entry.
7. Patient met all the lab requirements as descibed in Section 3.1.6 and 3.1.7.
8. Patient had a chest x-ray, chest CT, or whole body PET-CT within 70 days of study entry.
9. Patient had a contrast-enchanced CT or MRI of the adbomen and pelvis OR whole-body PET-CT (with or without contrast) within 90 days of study entry.
10. Patient had a prior invasive malignancy (except non-melanomatous skin cancer.
11. If yes, has the patient been disease free for a minimum of 3 years.
12. No distant metastases, based upon the following minimum diagnostic workup [NOTE: Patients with positive para-aortic nodes- completely resected, PET/CT negative are eligible]:
a.History/physical examination within 56 days prior to study entry
b.Contrast-enhanced imaging of the abdomen and pelvis by either CT, MRI, or PET-CT (whole
body) within 90 days prior to registration. (NOTE: whole body PET-CT is preferred)
c.Chest x-ray (PA and lateral) or chest CT within 70 days prior to study entry (except for those
who have had whole body PET-CT per Section 220.127.116.11).
13 .Age >= 18
14. CBC/differential obtained 14 days prior to study entry, with adequate bone marrow function defined as follows:
a. Absolute neutrophil count (ANC) >= 1,800 cells/mm3
b. Platelets >= 100,000 cells/mm3
c.Hemoglobin >= 10.0 g/dl (Note: The use of transfusion or other intervention to achieve Hgb >=
10.0 g/dl is acceptable.)
d.White blood cell count >= 4000 cells/mm3
15. Adequate hepatic and renal function defined as follows:
a. Serum creatinine <= 1.5 mg/dL within 14 days prior to study entry
b .Bilirubin <= 1.5 times normal 14 days prior to study entry
c. Alkaline phosphatase within upper limits of institutional normal within 14 days prior to study
d. ALT/SGPT and/or AST/SGOT within upper limits of institutional normal within 14 days prior to study entry
16. Patients with known HIV positive must have a CD4 cell count be >= 350 cells/mm3 within 14 days prior to study entry (note, however, that HIV testing is not required for entry into this protocol.) Excluding HIV positive patients with invasive cervical cancer and low CD4 cell counts is necessary because the treatments involved in this protocol may be significantly immunosuppressive.
17.Patient must provide study-specific informed consent prior to study entry.