GOG 240: A Randomized Phase III Trial of Cisplatin Plus Paclitaxel With and Without NCI-Supplied Bevacizumab (NSC #704865, IND #113912) Versus the Non-Platinum Doublet, Topotecan Plus Paclitaxel, With and Without NCI-Supplied Bevacizumab, In Stage IVB, Recurrent or Persistent Carcinoma of the Cervix
This is a multicenter study. Patients are stratified according to disease status (recurrent/persistent disease vs primary stage IVB disease), GOG performance status (0 vs 1), and prior platinum therapy as a radiosensitizer (yes vs no). Patients are randomized to 1 of 4 treatment arms.
?Arm I: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV on day 1 or 2.
?Arm II: Patients receive paclitaxel IV over 3 hours or 24 hours on day 1 and cisplatin IV and bevacizumab IV over 30-90 minutes on day 1 or 2.
?Arm III: Patients receive paclitaxel IV over 3 hours on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.
?Arm IV: Patients receive paclitaxel IV over 3 hours and bevacizumab IV over 30-90 minutes on day 1 and topotecan hydrochloride IV over 30 minutes on days 1-3.
In all arms, courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients complete quality-of-life questionnaires, including the FACT-Cx TOI, FACT/GOG-Ntx4, and Brief Pain Inventory, at baseline, before courses 2 and 5, and at 6 and 9 months after course 1. Patients also complete a smoking questionnaire at baseline.
About 6 people will take part in this study at UT Southwestern and Parkland Health & Hospital System. There will be approximately 130 patients will be involved in this research study throughout the United States and/or other countries.
After completion of study therapy, patients are followed every 3 months for 2 years and then every 6 months for 3 years.
1.Patients must have primary stage IVB, recurrent or persistent squamous cell carcinoma, adenosquamous carcinoma, or adenocarcinoma of the cervix which is not amenable to curative treatment with surgery and/or radiation therapy.
2.All patients must have measurable disease. Measurable disease is defined as at least one lesion that can be accurately measured in at least one dimension (longest dimension to be recorded). Each lesion must be >= 20 mm when measured by conventional techniques, including palpation, plain x-ray, CT, and MRI, or >= 10 mm when measured by spiral CT. Biopsy confirmation is required if the lesion(s) measures < 30 mm or if the treating physician determines it is clinically indicated. Patients must have at least one
* target lesion
* to be used to assess response on this protocol as defined by RECIST (Section 8.1). This lesion should be the one that was biopsied if one was performed. Tumors within a previously irradiated field will be designated as
* lesions unless progression is documented or a biopsy is obtained to confirm persistence at least 90 days following completion of radiation therapy.
3.Patients must have adequate:
oHematologic function: ANC >= 1500/mcl; platelets >= 100,000/mcl.
oRenal function: Patients with serum creatinine <= ULN (CTC Grade 0) or calculated creatinine clearance (Jeliffe Formula) >= 60 ml/min.
oHepatic function: bilirubin <= 1.5 x institutional normal; SGOT, alkaline phosphatase <= 2.5 x institutional normal.
oBlood coagulation parameters (PTT, PT/INR): PT such that international normalized ratio (INR) is <= 1.5 (or an in-range INR, usually between 2 and 3, if a patient is on a stable dose of therapeutic warfarin for management of venous thrombosis including pulmonary thromboembolus) and a PTT < 1.2 times the upper limit of normal.
oPatients must have a urine protein-creatinine ratio (UPC ratio) < 1.0.
4. Patients must have a GOG Performance Status of 0 or 1.
5. Patients must have recovered from the effects of surgery, radiation therapy, or chemoradiotherapy. At least six weeks must have elapsed from the last administration of chemoradiotherapy, and at least three weeks must have elapsed from the last administration of radiation therapy alone. At least six weeks must have elapsed from the time of any major surgical procedure prior to randomization.
6. Patients must have signed an approved informed consent and authorization permitting release of personal health information.
7.Patients must meet all of the pre-entry requirements specified in Section 7.0, including baseline QOL questionnaire.
8.Patients must be free of active infection requiring antibiotics.