NCT00941070

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
26

participants targeted

Target at below P25 for phase_2

Timeline
Completed

Started Jul 2009

Typical duration for phase_2

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

July 1, 2009

Completed
15 days until next milestone

First Submitted

Initial submission to the registry

July 16, 2009

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 17, 2009

Completed
2.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2012

Completed
3 months until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2012

Completed
11 months until next milestone

Results Posted

Study results publicly available

May 13, 2013

Completed
Last Updated

November 17, 2017

Status Verified

October 1, 2017

Enrollment Period

2.8 years

First QC Date

July 16, 2009

Results QC Date

March 20, 2013

Last Update Submit

October 16, 2017

Conditions

Recurrent Cervical CancerRecurrent Vaginal CancerStage IB Cervical CancerStage II Vaginal CancerStage IIA Cervical CancerStage IIB Cervical CancerStage III Cervical CancerStage III Vaginal CancerStage IVA Cervical CancerStage IVA Vaginal CancerStage IVB Cervical CancerStage IVB Vaginal CancerTherapy-related Toxicity

Outcome Measures

Primary Outcomes (1)

  • 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.

    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.

    post therapy at 3 months

Secondary Outcomes (11)

  • Clinical and Objective Response Assignment

    post therapy at 3 months

  • Clinical and Objective Response Assignment

    one month follow up assessment

  • Clinical and Objective Response Assignment

    three month follow up assessment

  • 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

    After 5 weeks of radiation therapy

  • Progression-free Survival

    at 18 months from study entry

  • +6 more secondary outcomes

Study Arms (1)

Treatment (cisplatin, triapine, radiation therapy)

EXPERIMENTAL

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: triapineDrug: cisplatinRadiation: external beam radiation therapyProcedure: quality-of-life assessmentOther: questionnaire administrationRadiation: fludeoxyglucose F 18Procedure: positron emission tomographyProcedure: computed tomography

Interventions

triapineDRUG

Given IV

Also known as: 3-AP, OCX-191
Treatment (cisplatin, triapine, radiation therapy)
cisplatinDRUG

Given IV

Also known as: CACP, CDDP, CPDD, DDP
Treatment (cisplatin, triapine, radiation therapy)
external beam radiation therapyRADIATION

Undergo pelvic external beam radiation therapy

Also known as: EBRT
Treatment (cisplatin, triapine, radiation therapy)
quality-of-life assessmentPROCEDURE

Ancillary studies

Also known as: quality of life assessment
Treatment (cisplatin, triapine, radiation therapy)
questionnaire administrationOTHER

Ancillary studies

Treatment (cisplatin, triapine, radiation therapy)
fludeoxyglucose F 18RADIATION

Undergo FDG-PET/CT

Also known as: 18FDG, FDG
Treatment (cisplatin, triapine, radiation therapy)
positron emission tomographyPROCEDURE

Undergo FDG-PET/CT

Also known as: FDG-PET, PET, PET scan, tomography, emission computed
Treatment (cisplatin, triapine, radiation therapy)
computed tomographyPROCEDURE

Undergo FDG-PET/CT

Also known as: tomography, computed
Treatment (cisplatin, triapine, radiation therapy)

Eligibility Criteria

Age18 Years+
Sexfemale
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Case Western Reserve University

Cleveland, Ohio, 44106, United States

Location

Related Publications (2)

  • Yun T, Liu Z, Wang J, Wang R, Zhu L, Zhu Z, Wang X. Microenvironment immune response induced by tumor ferroptosis-the application of nanomedicine. Front Oncol. 2022 Sep 16;12:1019654. doi: 10.3389/fonc.2022.1019654. eCollection 2022.

    PMID: 36185311DERIVED

  • Chao J, Synold TW, Morgan RJ Jr, Kunos C, Longmate J, Lenz HJ, Lim D, Shibata S, Chung V, Stoller RG, Belani CP, Gandara DR, McNamara M, Gitlitz BJ, Lau DH, Ramalingam SS, Davies A, Espinoza-Delgado I, Newman EM, Yen Y. A phase I and pharmacokinetic study of oral 3-aminopyridine-2-carboxaldehyde thiosemicarbazone (3-AP, NSC #663249) in the treatment of advanced-stage solid cancers: a California Cancer Consortium Study. Cancer Chemother Pharmacol. 2012 Mar;69(3):835-43. doi: 10.1007/s00280-011-1779-5. Epub 2011 Nov 22.

    PMID: 22105720DERIVED

MeSH Terms

Conditions

Uterine Cervical NeoplasmsVaginal Neoplasms

Interventions

3-aminopyridine-2-carboxaldehyde thiosemicarbazoneCisplatinFluorodeoxyglucose F18Magnetic Resonance Spectroscopy2-phenyl-6-(2'-(4'-(ethoxycarbonyl)thiazolyl))thiazolo(3,2-b)(1,2,4)triazole

Condition Hierarchy (Ancestors)

Uterine NeoplasmsGenital Neoplasms, FemaleUrogenital NeoplasmsNeoplasms by SiteNeoplasmsUterine Cervical DiseasesUterine DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital DiseasesVaginal Diseases

Intervention Hierarchy (Ancestors)

Chlorine CompoundsInorganic ChemicalsNitrogen CompoundsPlatinum CompoundsDeoxyglucoseDeoxy SugarsCarbohydratesSpectrum AnalysisChemistry Techniques, AnalyticalInvestigative Techniques

Results Point of Contact

Title
Dr. Charles Kunos
Organization
Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
kunosc@summahealth.org
330-375-4485

Study Officials

  • Charles Kunos

    Case Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Publication Agreements

PI is Sponsor Employee
No
Restriction Type
LTE60
Restrictive Agreement
Yes

Study Design

Study Type
interventional
Phase
phase 2
Allocation
NA
Masking
NONE
Purpose
TREATMENT
Intervention Model
SINGLE GROUP
Sponsor Type
NIH
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 16, 2009

First Posted

July 17, 2009

Study Start

July 1, 2009

Primary Completion

April 1, 2012

Study Completion

July 1, 2012

Last Updated

November 17, 2017

Results First Posted

May 13, 2013

Record last verified: 2017-10

Locations

US(1)