NCT02466971|Active Not RecruitingPhase 3ResultsFDA Drug

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

A Randomized Phase III Trial of Radiation Therapy and Cisplatin Alone or in Combination With Intravenous Triapine in Women With Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

National Cancer Institute (NCI)ClinicalTrials.gov

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3 other identifiers

NCI-2015-00835NRG-GY006U10CA180868

Study Type

interventional

Target

450

Locations

3 countries

Sites

382

Timeline

RegisteredJun 2015

StartedMay 2016

CompletionJul 2026

Brief 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.

Trial Health

On Track

Trial Health Score

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

Enrollment

450

participants targeted

Target at P50-P75 for phase_3

Timeline

2mo left

Started May 2016

Longer than P75 for phase_3

Geographic Reach

3 countries

382 active sites

Status

active not recruiting

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

10.2 years study duration

Study Progress98%

May 2016Jul 2026

First Submitted

Initial submission to the registry

June 5, 2015

Completed

4 days until next milestone

First Posted

Study publicly available on registry

June 9, 2015

Completed

11 months until next milestone

Study Start

First participant enrolled

May 10, 2016

Completed

6.7 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 26, 2023

Completed

11 months until next milestone

Results Posted

Study results publicly available

January 5, 2024

Completed

2.5 years until next milestone

Study Completion

Last participant's last visit for all outcomes

July 14, 2026

Expected

Last Updated

April 13, 2026

Status Verified

January 1, 2026

Enrollment Period

6.7 years

First QC Date

June 5, 2015

Results QC Date

November 2, 2023

Last Update Submit

April 9, 2026

Outcome Measures

Primary Outcomes (1)

Overall Survival (OS) Rate at 3 Years
Estimate for probability of overall survival at 3 years by Kaplan-Meier method, where overall survival is defined as the time from randomization to time of death due to any cause or the date of last contact, whichever occurs first.
At 3 years from randomization.

Secondary Outcomes (2)

Progression-free Survival (PFS) Rate at 3 Years
At 3 years from study randomization.
Number of Participants With Adverse Events (Grade 3 or Higher) During Treatment Period
During treatment period and up to 30 days after stopping the study treatment with a median treatment time as 53 days ranging from 1 to 189 days.

Other Outcomes (5)

Number of Participants With Hematologic Toxicity During Treatment Period
Up to 30 days after completion of study treatment
Number of Participants With Adverse Events (Grade 3 or Higher) That Occurred During Follow-Up Period
Up to 5 years
Peripheral Blood Methemoglobin
Baseline to 24 hours after triapine infusion
+2 more other outcomes

Study Arms (2)

Arm I (cisplatin, IMRT or RT, brachytherapy)

ACTIVE COMPARATOR

Patients receive cisplatin IV over 90 minutes on days 2, 9, 16, 23, 30, (and day 36 or 37 at the treating physician's discretion). Patients then undergo EBRT (either conventional RT or IMRT) QD 5 days a week for 25 fractions followed by LDR or HDR brachytherapy according to institution's standards. Treatment continues in the absence of disease progression or unacceptable toxicity.

Radiation: BrachytherapyDrug: CisplatinRadiation: External Beam Radiation TherapyRadiation: Intensity-Modulated Radiation TherapyOther: Laboratory Biomarker AnalysisRadiation: Radiation Therapy

Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

EXPERIMENTAL

Patients receive cisplatin and undergo EBRT followed by brachytherapy as in Arm I. Patients also receive triapine IV over 2 hours on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, 24, 26, 29, 31, and 33. Treatment continues in the absence of disease progression or unacceptable toxicity.

Radiation: BrachytherapyDrug: CisplatinRadiation: Intensity-Modulated Radiation TherapyOther: Laboratory Biomarker AnalysisRadiation: Radiation TherapyDrug: Triapine

Interventions

CisplatinDRUG

Given IV

Also known as: Abiplatin, Blastolem, Briplatin, CDDP, Cis-diammine-dichloroplatinum, Cis-diamminedichloridoplatinum, Cis-diamminedichloro Platinum (II), Cis-diamminedichloroplatinum, Cis-dichloroammine Platinum (II), Cis-platinous Diamine Dichloride, Cis-platinum, Cis-platinum II, Cis-platinum II Diamine Dichloride, Cismaplat, Cisplatina, Cisplatinum, Cisplatyl, Citoplatino, Citosin, Cysplatyna, DDP, Lederplatin, Metaplatin, Neoplatin, Peyrone's Chloride, Peyrone's Salt, Placis, Plastistil, Platamine, Platiblastin, Platiblastin-S, Platinex, Platinol, Platinol- AQ, Platinol-AQ, Platinol-AQ VHA Plus, Platinoxan, Platinum, Platinum Diamminodichloride, Platiran, Platistin, Platosin

Arm I (cisplatin, IMRT or RT, brachytherapy)Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

Laboratory Biomarker AnalysisOTHER

Correlative studies

Arm I (cisplatin, IMRT or RT, brachytherapy)Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

BrachytherapyRADIATION

Undergo brachytherapy

Also known as: Brachytherapy, NOS, Internal Radiation, Internal Radiation Brachytherapy, Internal Radiation Therapy, Radiation Brachytherapy, Radiation, Internal

Arm I (cisplatin, IMRT or RT, brachytherapy)Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

Intensity-Modulated Radiation TherapyRADIATION

Undergo IMRT

Also known as: IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy, Radiation, Intensity-Modulated Radiotherapy

Arm I (cisplatin, IMRT or RT, brachytherapy)Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

Radiation TherapyRADIATION

Undergo conventional RT

Also known as: Cancer Radiotherapy, Energy Type, ENERGY_TYPE, Irradiate, Irradiated, Irradiation, Radiation, Radiation Therapy, NOS, Radiotherapeutics, Radiotherapy, RT, Therapy, Radiation

Arm I (cisplatin, IMRT or RT, brachytherapy)Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

TriapineDRUG

Given IV

Also known as: 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, 3-Apct, OCX-0191, OCX-191, OCX191, PAN-811

Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)

External Beam Radiation TherapyRADIATION

Undergo EBRT

Also known as: Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy, External Beam Radiotherapy (conventional), External Beam RT, external radiation, External Radiation Therapy, external-beam radiation, Radiation, External Beam, Teleradiotherapy, Teletherapy, Teletherapy Radiation

Arm I (cisplatin, IMRT or RT, brachytherapy)

Eligibility Criteria

Age18 Years+

Sexfemale

Healthy VolunteersNo

Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

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
+3 more criteria

You may not qualify if:

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

Contact the study team to confirm eligibility.

Sponsors & Collaborators

NRG Oncologycollaborator
National Cancer Institute (NCI)lead

Study Sites (382)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Anchorage Associates in Radiation Medicine

Anchorage, Alaska, 98508, United States

Location

Alaska Breast Care and Surgery LLC