Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers

Inclusion Criteria:

• Patient has a new, unrated histologic diagnosis of stage IB2 (> 4 cm), II, IIIB orIVA squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix (FIGO

2009. or stage II-IVA squamous, adenocarcinoma, or adenosquamous carcinoma of thevagina not amenable to curative surgical resection alone; the presence or absence ofpara-aortic lymph node metastasis will be based on pre-therapy 18F-FDG PET/CT; NOTE:if the baseline 18F-FDG PET/CT identifies hypermetabolic para-aortic disease, suchpatients will NOT be eligible; the patient must be able to tolerate imagingrequirements 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 Xinstitutional 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 forcisplatin if the estimated creatinine clearance (CCr) is >= 30 ml/min; for thepurpose of estimating the CCr, the formula of Cockcroft and Gault for femalesshould 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, testingoptional); known HIV-positive patients receiving combination antiretroviral therapyare ineligible because of the potential for pharmacokinetic interactions withtriapine

• Patient does not have a known allergy to compounds of similar or biologiccomposition as triapine

• Patient does not have known glucose-6-phosphate dehydrogenase (G6PD) deficiency asthe condition interferes with triapine antidote metabolism (G6PD testing optional)

• Patient is not actively breastfeeding (or has agreed to discontinue breastfeedingbefore the initiation of protocol therapy)

Exclusion Criteria:

• Patient has another concurrent active invasive malignancy

• Patient has had a prior invasive malignancy diagnosed within the last three years (except [1] non-melanoma skin cancer or [2] prior in situ carcinoma of the cervix);patients are excluded if they have received prior pelvic radiotherapy for any reasonthat would contribute radiation dose that would exceed tolerance of normal tissuesat the discretion of the treating physician

• Patient has uncontrolled intercurrent illness including, but not limited to,symptomatic congestive heart failure, unstable angina pectoris, myocardialinfarction within six months of protocol initiation, cardiac arrhythmia within sixmonths of protocol initiation; known inadequately controlled hypertension;clinically significant pulmonary disease including dyspnea at rest, or patientsrequiring supplemental oxygen, or poor pulmonary reserve; or clinically significantrenal function impairment (baseline serum creatinine > 2 mg/dL); or psychiatricillness/social situations that would limit compliance with study requirements

• Patient is receiving another investigational agent for the treatment of cancer

• Patient is currently pregnant

• Patient does not agree to use two forms of birth control if they are ofchild-bearing potential

• Patients who have had a hysterectomy or are planning to have an adjuvanthysterectomy following radiation as part of their cervical cancer treatment areineligible (05/30/2017)

• Patients scheduled to be treated with adjuvant consolidation chemotherapy or otheranti-neoplastic therapy at the conclusion of their standard chemoradiation (05/30/2017)

• Patients with self-reported or known diagnosis of G6PD deficiency (05/30/2017)

• Patients with vaginal cancer may have previously undergone a hysterectomy forvarious indications; patients with vaginal cancer who underwent a hysterectomy fortreatment of cervical cancer less than five years prior to their diagnosis ofvaginal cancer are ineligible