Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

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Brief Title

Triapine, Cisplatin, and Radiation Therapy in Treating Patients With Cervical Cancer or Vaginal Cancer

Official Title

A Phase 2 Study of Triapine® (NSC #663249) and Cisplatin in Combination With Pelvic Radiation for Treatment of Stage IB2-IVa Cervical Cancer or Stage II-IV Vaginal Cancer

Brief 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.
    

Detailed Description

      PRIMARY OBJECTIVES:

      I. To determine three-month fasting F-18 fluorodeoxyglucose (FDG) positron emission
      tomography (PET/CT) imaging complete metabolic response as defined by the European
      Organization for Research and Treatment of Cancer (EORTC) PET study group.

      SECONDARY OBJECTIVES:

      I. To determine 6-month progression-free survival rate as calculated from the date of first
      treatment until date of disease progression, relapse, or death.

      II. To quantitate change in pre-treatment standard uptake value (SUV) on PET/CT and
      post-treatment PET/CT or disease progression PET/CT.

      III. To quantitate pre-treatment, during treatment and 3-mo post-treatment grade 2 or higher
      gastrointestinal, genitourinary, and sexual function toxicity resulting from Triapine®,
      cisplatin, and radiation therapy as measured by CTCAE v3.0, which will be utilized until
      December 31, 2010; CTCAE v4.0 will be utilized beginning January 1, 2011.

      IV. To associate smoking habit (non-smoker, smoker who quit during therapy, smoker) with 3-mo
      post-treatment PET/CT metabolic response and 3-mo best overall clinical response as measured
      by RECIST criteria after Triapine®, cisplatin, and radiation therapy.

      V. To associate HPV or non-HPV sub-type cervical cancer with 3-mo post-treatment PET/CT
      metabolic response and 3-mo best overall clinical response as measured by RECIST criteria
      after Triapine®, cisplatin, and radiation therapy.

      OUTLINE: This is a multicenter study. Patients are stratified according to brachytherapy
      treatment (planned intracavitary brachytherapy vs none).

      Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, and 30 and triapine IV on
      days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Patients also undergo pelvic
      external beam radiotherapy 5 days a week during weeks 1-5. Patients may undergo parametrial
      boost radiation and intracavitary low-dose or high-dose rate brachytherapy as clinically
      indicated.

      Patients undergo whole-body F-18 fluorodeoxyglucose-PET/CT imaging at baseline, at 3 months
      after completion of study treatment, and at disease progression. Patients complete Sexual
      Function-Vaginal Changes Questionnaire and a smoking behavior questionnaire at baseline, at 3
      months after completion of study treatment, and at disease progression.

      After completion of study treatment, patients are followed periodically for up to 5 years.
    

Study Phase

Phase 2

Study Type

Interventional


Primary Outcome

Fasting F-18 Fluorodeoxyglucose (FDG) Positron Emission Tomography (PET/CT) Imaging Complete Metabolic Response, Reported Following National Cancer Institute (NCI) and European Organization for Research and Treatment of Cancer (EORTC) Guidelines.

Secondary Outcome

 Clinical and Objective Response Assignment

Condition

Recurrent Cervical Cancer

Intervention

triapine

Study Arms / Comparison Groups

 Treatment (cisplatin, triapine, radiation therapy)
Description:  Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, and 30 and triapine IV on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Patients also undergo pelvic external beam radiotherapy 5 days a week during weeks 1-5. Patients may undergo parametrial boost radiation and intracavitary low-dose or high-dose rate brachytherapy as clinically indicated.
Patients undergo whole-body F-18 fluorodeoxyglucose-PET/CT imaging at baseline, at 3 months after completion of study treatment, and at disease progression. Patients complete Sexual Function-Vaginal Changes Questionnaire and a smoking behavior questionnaire at baseline, at 3 months after completion of study treatment, and at disease progression.

Publications

* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.

Recruitment Information


Recruitment Status

Drug

Estimated Enrollment

26

Start Date

July 2009

Completion Date

July 2012

Primary Completion Date

April 2012

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
      

Gender

Female

Ages

18 Years - N/A

Accepts Healthy Volunteers

No

Contacts

Charles Kunos, , 

Location Countries

United States

Location Countries

United States

Administrative Informations


NCT ID

NCT00941070

Organization ID

NCI-2012-02896

Secondary IDs

NCI-2012-02896

Responsible Party

Sponsor

Study Sponsor

National Cancer Institute (NCI)


Study Sponsor

Charles Kunos, Principal Investigator, Case Comprehensive Cancer Center


Verification Date

October 2017