Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer
Condition: Recurrent Cervical Cancer; Recurrent Vaginal Cancer; Stage IB Cervical Cancer; Stage II Vaginal Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage III Vaginal Cancer; Stage IVA Cervical Cancer; Stage IVA Vaginal Cancer; Stage IVB Cervical Cancer; Stage IVB Vaginal Cancer; Therapy-related Toxicity
MeSH terms: Uterine Cervical Neoplasms; Vaginal Neoplasms; Recurrence
Intervention: triapine; cisplatin; external beam radiation therapy; quality-of-life assessment; questionnaire administration; fludeoxyglucose F 18; positron emission tomography; computed tomography
Intervention description: Given IV; Given IV; Undergo pelvic external beam radiation therapy; Ancillary studies; Ancillary studies; Undergo FDG-PET/CT; Undergo FDG-PET/CT; Undergo FDG-PET/CT
Intervention MeSH terms: Fluorodeoxyglucose F18
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 26.0
Sex: Female
Minimum age: 18 Years
Healthy volunteers: No

Summary:

      This phase II trial is studying how triapine and cisplatin given together with radiation
      therapy works in treating patients with cervical cancer or vaginal cancer. Triapine may stop
      the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used
      in chemotherapy, such as cisplatin, work in different ways to stop the growth of tumor cells,
      either by killing the cells or by stopping them from dividing. Radiation therapy uses
      high-energy x-rays to kill tumor cells. Giving triapine together with cisplatin may make
      tumor cells more sensitive to radiation therapy.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Female patients must have histologically confirmed (tumor tissue biopsy) primary
             clinical stage IB2-IVB cervical cancer or clinical stage II-IVB vaginal cancer not
             amenable to curative surgical resection alone to be eligible; patients with stage IVB
             cervical cancer may receive systemic chemotherapy for treatment of metastatic disease
             a) after the 3-month post-therapy PET scan and b) if the 3-month post-therapy PET scan
             documents progressive disease at the discretion of the treating physician

          -  Patients with other active invasive malignancies are excluded; patients with prior
             malignancies (except non-melanoma skin cancer or prior in situ carcinoma of the
             cervix, patients with synchronous or past history of primary endometrial cancer
             meeting all conditions of a) stage not greater than IB, b) no more than superficial
             myometrial invasion, c) without vascular or lymphatic invasion, and d) no poorly
             differentiated subtypes including papillary serous, clear cell or other FIGO grade 3
             lesions; patients with other invasive malignancies who had (or have) cancer present
             within the last five years are excluded; patients are excluded if they have received
             prior low abdominal or pelvic radiotherapy for any reason that would contribute
             radiation dose that would exceed tolerance of normal tissues

          -  Life expectancy of greater than 3 months

          -  Absolute neutrophil count >= 1,500/uL

          -  Platelets >= 100,000/uL

          -  Hemoglobin >= 10 g/dL

          -  Total bilirubin =< 2.0 mg/dL

          -  AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal

          -  PT/aPTT =< 1.5 X institutional upper limit of normal

          -  Patients should have a serum creatinine =< 1.5mg/dL to receive weekly intravenous
             cisplatin chemotherapy

               -  Patients whose serum creatinine is between 1.5 and 1.9 mg/dL are eligible for
                  cisplatin chemotherapy if the estimated creatinine clearance is >= 30 ml/min;
                  patients eligible for cisplatin chemotherapy using the criteria for creatinine
                  clearance may also receive intravenous Triapine®

          -  Women of child-bearing potential and male partners must agree to use adequate
             contraception (hormonal or barrier method of birth control; abstinence) prior to study
             entry and for the duration of study participation; should a woman become pregnant or
             suspect she is pregnant while participating in this study, she should inform her
             treating physician immediately

          -  Patients must demonstrate ability to understand and the willingness to sign a written
             informed consent document

        Exclusion Criteria:

          -  Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for
             nitrosoureas or mitomycin C) prior to entering the study or those who have not
             recovered from adverse events due to agents administered more than 4 weeks earlier are
             excluded

          -  Patients may not be receiving any other investigational agents

          -  Patients with known brain metastases should be excluded from this clinical trial
             because of their poor prognosis and because they often develop progressive
             neurological dysfunction that would confound the evaluation of neurological and other
             adverse events

          -  History of allergic reactions attributed to compounds of similar chemical or biologic
             composition to Triapine® or other agents used in study

          -  Patients unable to receive intravenous chemotherapies as a consequence of poor
             vascular access are ineligible

          -  Uncontrolled intercurrent illness including, but not limited to, ongoing or active
             infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac
             arrhythmia, known inadequately controlled hypertension, significant pulmonary disease
             including dyspnea at rest, patients requiring supplemental oxygen, or poor pulmonary
             reserve; proteinuria or clinically significant renal function impairment (baseline
             serum creatinine > 2mg/dL), or psychiatric illness/social situations that would limit
             compliance with study requirements are excluded

          -  Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded
             as the antidote methylene blue for Triapine® toxicity may be at best ineffective in
             such patients and may have the potential to complicate the clinical situation by
             provoking hemolysis

          -  Pregnant women are excluded from this study because Triapine® is a heterocyclic
             carboxaldehyde thiosemicarbazone with the potential for teratogenic or abortifacient
             effects; screening beta-hcg levels and diagnostic tests will be used to determine
             eligibility; because there is an unknown but potential risk for adverse events in
             nursing infants secondary to treatment of the mother with Triapine®, breastfeeding
             should be discontinued if the mother is treated with Triapine®; these potential risks
             may also apply to other agents used in this study

          -  Patients not willing to agree to use appropriate contraception while on trial will be
             excluded

          -  HIV-positive patients on combination antiretroviral therapy are ineligible because of
             the potential for pharmacokinetic interactions with Triapine®; in addition, these
             patients are at increased risk of lethal infections when treated with
             marrow-suppressive therapy; appropriate studies will be undertaken in patients
             receiving combination antiretroviral therapy when indicated; HIV testing is not
             mandatory; patients that are known to be HIV-positive are ineligible if they are
             receiving combination antiretroviral therapy