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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Cancer Institute (NCI)
ClinicalTrials.gov Identifier:
NCT00941070
First received: July 16, 2009
Last updated: April 21, 2014
Last verified: December 2012
  Purpose

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.


Condition Intervention Phase
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
Drug: triapine
Drug: cisplatin
Radiation: external beam radiation therapy
Procedure: quality-of-life assessment
Other: questionnaire administration
Radiation: fludeoxyglucose F 18
Procedure: positron emission tomography
Procedure: computed tomography
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • 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. [ Time Frame: post therapy at 3 months ] [ Designated as safety issue: No ]
    To quantitate change in pre-treatment standard uptake value (SUV) on PET/CT and posttreatment PET/CT or disease progression PET/CT. Change in PET/CT SUV will be associated with 3-month best overall clinical response.


Secondary Outcome Measures:
  • Clinical and Objective Response Assignment [ Time Frame: post therapy at 3 months ] [ Designated as safety issue: No ]
    Number of patients with a complete clinical responses defined as disappearance of all target lesions. A complete metabolic response on PET/CT will be defined as absence of abnormal FDG uptake at sites of abnormal FDG uptake noted on pre-treatment FDG-PET study.

  • Clinical and Objective Response Assignment [ Time Frame: one month follow up assessment ] [ Designated as safety issue: No ]
    Number of patients with a complete clinical responses defined as disappearance of all target lesions. A complete metabolic response on PET/CT will be defined as absence of abnormal FDG uptake at sites of abnormal FDG uptake noted on pre-treatment FDG-PET study.

  • Clinical and Objective Response Assignment [ Time Frame: three month follow up assessment ] [ Designated as safety issue: No ]
    Number of patients with a complete clinical responses defined as disappearance of all target lesions. A complete metabolic response on PET/CT will be defined as absence of abnormal FDG uptake at sites of abnormal FDG uptake noted on pre-treatment FDG-PET study.

  • Percent of Patients With Incidence of Grade 2 or Higher Gastrointestinal and Genitourinary Toxicity, Assessed Using CTCAE v3.0 Until December 31, 2010 and CTCAE v4.0 Beginning January 1, 2011 [ Time Frame: After 5 weeks of radiation therapy ] [ Designated as safety issue: Yes ]
    Information will include the type, severity, time of onset, time of resolution, and the probable association with the study regimen. Frequency tables will be constructed to summarize observed incidence by severity and type of toxicity.

  • Progression-free Survival [ Time Frame: at 18 months from study entry ] [ Designated as safety issue: No ]
    Percentage of patients that did not have disease progression. Estimates of progression-free survival will be computed using the product-limit estimate of Kaplan and Meier.

  • PET/CT Scan Metabolic Activity [ Time Frame: Baseline (pre-therapy) ] [ Designated as safety issue: No ]
    Descriptive tabular data reporting mean, standard deviation, minimum, maximum provided by metabolic response cohort. Status of 3-month post-treatment metabolic response associated with clinical response measured by RECIST criteria and with overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation used. Tests of equivalence of the estimates compared using the Wilcoxon long-rank test using P 0.05. Cox proportional hazards regression models used in multivariate analyses.

  • PET/CT Scan Metabolic Activity [ Time Frame: 3 months post-treatment ] [ Designated as safety issue: No ]
    Descriptive tabular data reporting mean, standard deviation, minimum, maximum provided by metabolic response cohort. Status of 3-month post-treatment metabolic response associated with clinical response measured by RECIST criteria and with overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation used. Tests of equivalence of the estimates compared using the Wilcoxon long-rank test using P 0.05. Cox proportional hazards regression models used in multivariate analyses.

  • PET/CT Scan Metabolic Activity [ Time Frame: Up to 5 years ] [ Designated as safety issue: No ]
    Descriptive tabular data reporting mean, standard deviation, minimum, maximum provided by metabolic response cohort. Status of 3-month post-treatment metabolic response associated with clinical response measured by RECIST criteria and with overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation used. Tests of equivalence of the estimates compared using the Wilcoxon long-rank test using P 0.05. Cox proportional hazards regression models used in multivariate analyses.

  • Change in Sexual Function, Assessed Using the Sexual Function-Vaginal Changes Questionnaire [ Time Frame: Baseline to up to 5 years ] [ Designated as safety issue: No ]
  • Change in Smoking Behavior, Assessed Using the Smoking Questionnaire and Cessation Counseling [ Time Frame: 18 months from study entry ] [ Designated as safety issue: No ]
  • Progression Free Survival by HPV Subtype [ Time Frame: Baseline ] [ Designated as safety issue: No ]
    Tabular descriptive data will be presented. HPV sub-type will be associated with treatment related toxicity, clinical response, PET metabolic response, and overall clinical outcome. Kaplan-Meier (product-limit) method of survival estimation will be used. Tests of equivalence of the estimates will be compared using the Wilcoxon long-rank test using a threshold for statistical significance of P 0.05. Cox proportional hazards regression models will be used in multivariate analyses.


Enrollment: 26
Study Start Date: July 2009
Study Completion Date: July 2012
Primary Completion Date: April 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (cisplatin, triapine, radiation therapy)

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.

Drug: triapine
Given IV
Other Names:
  • 3-AP
  • OCX-191
Drug: cisplatin
Given IV
Other Names:
  • CACP
  • CDDP
  • CPDD
  • DDP
Radiation: external beam radiation therapy
Undergo pelvic external beam radiation therapy
Other Name: EBRT
Procedure: quality-of-life assessment
Ancillary studies
Other Name: quality of life assessment
Other: questionnaire administration
Ancillary studies
Radiation: fludeoxyglucose F 18
Undergo FDG-PET/CT
Other Names:
  • 18FDG
  • FDG
Procedure: positron emission tomography
Undergo FDG-PET/CT
Other Names:
  • FDG-PET
  • PET
  • PET scan
  • tomography, emission computed
Procedure: computed tomography
Undergo FDG-PET/CT
Other Name: tomography, computed

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00941070

Locations
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44106
Sponsors and Collaborators
Investigators
Principal Investigator: Charles Kunos Case Comprehensive Cancer Center
  More Information

No publications provided by National Cancer Institute (NCI)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00941070     History of Changes
Other Study ID Numbers: NCI-2012-02896, NCI-2012-02896, CDR0000647544, CASE 11808, 8327, P30CA043703, U01CA062502
Study First Received: July 16, 2009
Results First Received: March 20, 2013
Last Updated: April 21, 2014
Health Authority: United States: Food and Drug Administration

Additional relevant MeSH terms:
Vaginal Neoplasms
Uterine Cervical Diseases
Uterine Diseases
Genital Diseases, Female
Vaginal Diseases
Uterine Cervical Neoplasms
Uterine Neoplasms
Genital Neoplasms, Female
Urogenital Neoplasms
Neoplasms by Site
Neoplasms
Cisplatin
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Radiation-Sensitizing Agents
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on July 28, 2014