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
Condition: Advanced Vaginal Adenocarcinoma; Advanced Vaginal Adenosquamous Carcinoma; Advanced Vaginal Squamous Cell Carcinoma; Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Squamous Cell Carcinoma; Stage IB2 Cervical Cancer AJCC v6 and v7; Stage II Cervical Cancer AJCC v7; Stage II Vaginal Cancer AJCC v6 and v7; Stage IIA Cervical Cancer AJCC v7; Stage IIB Cervical Cancer AJCC v6 and v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IV Vaginal Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vaginal Cancer AJCC v6 and v7; Unresectable Vaginal Carcinoma; Vaginal Adenocarcinoma; Vaginal Adenosquamous Carcinoma; Vaginal Carcinoma; Vaginal Squamous Cell Carcinoma, Not Otherwise Specified
MeSH terms: Carcinoma; Carcinoma, Squamous Cell; Adenocarcinoma; Uterine Cervical Neoplasms; Vaginal Neoplasms; Carcinoma, Adenosquamous
Intervention: Brachytherapy; Cisplatin; External Beam Radiation Therapy; Intensity-Modulated Radiation Therapy; Laboratory Biomarker Analysis; Radiation Therapy; Triapine
Intervention description: Undergo brachytherapy; Given IV; Undergo EBRT; Undergo IMRT; Correlative studies; Undergo conventional RT; Given IV
Intervention MeSH terms: Cisplatin
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 450.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      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.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Patient has a new, unrated histologic diagnosis of stage IB2 (> 4 cm), II, IIIB or IVA
             squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix (FIGO 2009)
             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; NOTE: 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 because of the potential for pharmacokinetic interactions with triapine

          -  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 as the
             condition interferes with triapine antidote metabolism (G6PD testing optional)

          -  Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding
             before 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 reason
             that would contribute radiation dose that would exceed tolerance of normal tissues at
             the discretion of the treating physician

          -  Patient has uncontrolled intercurrent illness including, but not limited to,
             symptomatic congestive heart failure, unstable angina pectoris, myocardial infarction
             within six months of protocol initiation, cardiac arrhythmia within six months of
             protocol initiation; known inadequately controlled hypertension; clinically
             significant pulmonary disease including dyspnea at rest, or patients requiring
             supplemental oxygen, or poor pulmonary reserve; or clinically significant renal
             function impairment (baseline serum creatinine > 2 mg/dL); or psychiatric
             illness/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 of child-bearing
             potential

          -  Patients who have had a hysterectomy or are planning to have an adjuvant hysterectomy
             following radiation as part of their cervical cancer treatment are ineligible
             (05/30/2017)

          -  Patients scheduled to be treated with adjuvant consolidation chemotherapy or other
             anti-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 for various
             indications; patients with vaginal cancer who underwent a hysterectomy for treatment
             of cervical cancer less than five years prior to their diagnosis of vaginal cancer are
             ineligible