A Randomized Phase II Trial of Radiation Therapy and Cisplatin Alone or in Combination with Intravenous Triapine in Women with Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer
Overview
This randomized phase III trial studies radiation therapy and cisplatin with triapine to see how well they work compared to the standard radiation therapy and cisplatin alone in treating patients with newly diagnosed stage IB2, II, or IIIB-IVA cervical cancer or stage II-IVA vaginal cancer. Radiation therapy uses high energy protons to kill tumor cells and shrink tumors. 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. Triapine may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. It is not yet known whether radiation therapy and cisplatin are more effective with triapine in treating cervical or vaginal cancer.
Key Inclusion Criteria
For a patient to be eligible for participation in this study, all of the following criteria must apply.
- Patient has a new, unrated histologic diagnosis of stage IB2 (> 5 cm), II, IIIB or IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix or stage II-IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the vagina not amenable to curative surgical resection alone ; the presence or absence of para‐aortic lymph node metastasis will be based on pre-therapy 18F‐FDG PET/CT; if the baseline 18F‐FDG PET/CT identifies hypermetabolic para‐aortic disease, such patients will NOT be eligible; the patient must be able to tolerate imaging requirements of an 18F‐FDG PET/CT scan
- Patient must provide study specific informed consent prior to study entry
- Patient must have a Gynecologic Oncology Group (GOG) performance status of 0, 1, or 2 or equivalent
- Absolute neutrophil count > 1,500/uL
- Platelets > 100,000/uL
- Hemoglobin > 10 g/dL
- Total bilirubin < 2.0 mg/dL
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) < 2.5 X institutional upper limit of normal
- Prothrombin time (PT)/activated partial thromboplastin time (aPTT) < 1.5 X institutional upper limit of normal
- Creatinine =< 1.5 mg/dL to receive weekly cisplatin
- Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for cisplatin if the estimated creatinine clearance (CCr) is >= 30 ml/min; for the purpose of estimating the CCr, the formula of Cockcroft and Gault for females should be used
- Patient does not have uncontrolled diabetes mellitus (i.e., fasting blood glucose > 200 mg/dL)
- Patient has a life expectancy of greater than 20 weeks
- Patient does not have known brain metastases (testing optional)
- Patient does not have known human immunodeficiency virus syndrome (HIV, testing optional); known HIV-positive patients receiving combination antiretroviral therapy are ineligible
- Patient does not have a known allergy to compounds of similar or biologic composition as triapine
- Patient does not have known glucose‐6‐phosphate dehydrogenase (G6PD) deficiency (G6PD testing optional)
- Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding before the initiation of protocol therapy)
Key Exclusion Criteria
A patient will not be eligible for participation in this study if any of the following criteria apply.
- Patients with recurrent carcinoma of the vulva regardless of previous treatment
- Patients who have received prior pelvic radiation or cytotoxic chemotherapy
- Patients with vulvar melanomas or sarcomas
- Patients with circumstances that will not permit completion of the study or the required follow-up
- Patients with evidence of active septicemia, severe infection, gastrointestinal bleeding or severe gastrointestinal symptoms requiring medical or surgical therapy
- 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
Learn More
To learn more, visit ClinicalTrials.Gov
Study Type
Phase III
Principal Investigator(s)
Carlton Schwab, MD
Sponsor(s)
National Cancer Institute (NCI)