Purpose

This randomized phase II 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.

Conditions

Eligibility

Eligible Ages
Over 18 Years
Eligible Genders
Female
Accepts Healthy Volunteers
No

Inclusion Criteria

  • Patient has a new, unrated histologic diagnosis of stage IB2 (> 5 cm), II, IIIB or IVA squamous, adenocarcinoma, or adenosquamous carcinoma of the uterine cervix 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; 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
  • Patient does not have a known allergy to compounds of similar or biologic composition as triapine
  • Patient does not have known glucose‐6‐phosphate dehydrogenase (G6PD) deficiency (G6PD testing optional)
  • Patient is not actively breastfeeding (or has agreed to discontinue breastfeeding before the initiation of protocol therapy)

Exclusion Criteria

  • 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; proteinuria 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 must 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
  • Patients scheduled to be treated with adjuvant consolidation chemotherapy at the conclusion of their standard chemoradiation
  • Patients with self-reported or known diagnosis of G6PD deficiency

Study Design

Phase
Phase 2
Study Type
Interventional
Allocation
Randomized
Intervention Model
Parallel Assignment
Primary Purpose
Treatment
Masking
None (Open Label)

Arm Groups

ArmDescriptionAssigned Intervention
Active Comparator
Arm I (cisplatin, IMRT or RT, brachytherapy)
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.
  • Drug: Cisplatin
    Given IV
    Other names:
    • 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
  • Radiation: External Beam Radiation Therapy
    Undergo EBRT
    Other names:
    • Definitive Radiation Therapy
    • EBRT
    • External Beam Radiotherapy
    • External Beam RT
    • external radiation
    • External Radiation Therapy
    • external-beam radiation
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
  • Radiation: Internal Radiation Therapy
    Undergo brachytherapy
    Other names:
    • BRACHYTHERAPY
    • internal radiation
    • Internal Radiation Brachytherapy
    • Radiation Brachytherapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Radiation: Radiation Therapy
    Undergo conventional RT
    Other names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • irradiation
    • Radiation
    • Radiotherapeutics
    • RADIOTHERAPY
    • RT
    • Therapy, Radiation
Experimental
Arm II (cisplatin, IMRT or RT, brachytherapy, triapine)
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.
  • Drug: Cisplatin
    Given IV
    Other names:
    • 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
  • Radiation: Intensity-Modulated Radiation Therapy
    Undergo IMRT
    Other names:
    • IMRT
    • Intensity Modulated RT
    • Intensity-Modulated Radiotherapy
  • Radiation: Internal Radiation Therapy
    Undergo brachytherapy
    Other names:
    • BRACHYTHERAPY
    • internal radiation
    • Internal Radiation Brachytherapy
    • Radiation Brachytherapy
  • Other: Laboratory Biomarker Analysis
    Correlative studies
  • Radiation: Radiation Therapy
    Undergo conventional RT
    Other names:
    • Cancer Radiotherapy
    • Irradiate
    • Irradiated
    • irradiation
    • Radiation
    • Radiotherapeutics
    • RADIOTHERAPY
    • RT
    • Therapy, Radiation
  • Drug: Triapine
    Given IV
    Other names:
    • 3-aminopyridine-2-carboxaldehyde thiosemicarbazone
    • 3-AP
    • 3-Apct
    • OCX-191

Recruiting Locations

University of Alabama at Birmingham Cancer Center
Birmingham, Alabama 35233
Contact:
Site Public Contact
205-934-0220
tmyrick@uab.edu

The University of Arizona Medical Center-University Campus
Tucson, Arizona 85724
Contact:
Site Public Contact
520-626-9008

University of Arkansas for Medical Sciences
Little Rock, Arkansas 72205
Contact:
Site Public Contact
501-686-8274

UC San Diego Moores Cancer Center
La Jolla, California 92093
Contact:
Site Public Contact
858-822-5354
cancercto@ucsd.edu

University of Colorado Hospital
Aurora, Colorado 80045
Contact:
Site Public Contact
720-848-0650

University of Florida Health Science Center - Gainesville
Gainesville, Florida 32610
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

Moffitt Cancer Center
Tampa, Florida 33612
Contact:
Site Public Contact
800-456-7121
canceranswers@moffitt.org

Emory University Hospital Midtown
Atlanta, Georgia 30308
Contact:
Site Public Contact
888-946-7447

Emory University Hospital/Winship Cancer Institute
Atlanta, Georgia 30322
Contact:
Site Public Contact
404-778-1868

Emory Saint Joseph's Hospital
Atlanta, Georgia 30342
Contact:
Site Public Contact
412-339-5294
Roster@nrgoncology.org

John H Stroger Jr Hospital of Cook County
Chicago, Illinois 60612
Contact:
Site Public Contact
312-864-5204

Rush University Medical Center
Chicago, Illinois 60612
Contact:
Site Public Contact
312-942-5498
clinical_trials@rush.edu

Loyola University Medical Center
Maywood, Illinois 60153
Contact:
Site Public Contact
708-226-4357

Parkview Hospital Randallia
Fort Wayne, Indiana 46805
Contact:
Site Public Contact
260-373-8888
parkviewresearch@parkview.com

Saint Vincent Hospital and Health Care Center
Indianapolis, Indiana 46260
Contact:
Site Public Contact
317-338-2194
research@stvincent.org

University of Kansas Cancer Center
Kansas City, Kansas 66160
Contact:
Site Public Contact
913-945-7552
ctnursenav@kumc.edu

East Jefferson General Hospital
Metairie, Louisiana 70006
Contact:
Site Public Contact
504-210-3539
trials@jeffradonc.com

Cooper Hospital University Medical Center
Camden, New Jersey 08103
Contact:
Site Public Contact
856-325-6757

University of New Mexico Cancer Center
Albuquerque, New Mexico 87102
Contact:
Site Public Contact
505-925-0366
LByatt@nmcca.org

Roswell Park Cancer Institute
Buffalo, New York 14263
Contact:
Site Public Contact
800-767-9355
askroswell@roswellpark.org

Mount Sinai Chelsea
New York, New York 10011
Contact:
Site Public Contact
212-824-7309
CCTO@mssm.edu

Laura and Isaac Perlmutter Cancer Center at NYU Langone
New York, New York 10016
Contact:
Site Public Contact
212-263-4434
prmc.coordinator@nyumc.org

State University of New York Upstate Medical University
Syracuse, New York 13210
Contact:
Site Public Contact
315-464-5476

Miami Valley Hospital South
Centerville, Ohio 45459
Contact:
Site Public Contact
937-775-1350
som_dcop@wright.edu

Case Western Reserve University
Cleveland, Ohio 44106
Contact:
Site Public Contact
800-641-2422
CTUReferral@UHhospitals.org

Cleveland Clinic Foundation
Cleveland, Ohio 44195
Contact:
Site Public Contact
866-223-8100
CancerAnswer@ccf.org

Legacy Good Samaritan Hospital and Medical Center
Portland, Oregon 97210
Contact:
Site Public Contact
800-220-4937
cancer@lhs.org

Reading Hospital
West Reading, Pennsylvania 19611
Contact:
Site Public Contact
610-988-9323

Women and Infants Hospital
Providence, Rhode Island 02905
Contact:
Site Public Contact
401-274-1122

Saint Francis Cancer Center
Greenville, South Carolina 29607
Contact:
Site Public Contact
864-603-6213
meissa_beckman@bshsi.org

Spartanburg Medical Center
Spartanburg, South Carolina 29303
Contact:
Site Public Contact
864-560-6104
kmertz-rivera@gibbscc.org

Vanderbilt University/Ingram Cancer Center
Nashville, Tennessee 37232
Contact:
Site Public Contact
800-811-8480

UT Southwestern/Simmons Cancer Center-Dallas
Dallas, Texas 75390
Contact:
Site Public Contact
214-648-7097
canceranswerline@UTSouthwestern.edu

Memorial Hermann Texas Medical Center
Houston, Texas 77030
Contact:
Site Public Contact
713-792-3245

Seattle Cancer Care Alliance
Seattle, Washington 98109
Contact:
Site Public Contact
800-804-8824

MultiCare Tacoma General Hospital
Tacoma, Washington 98405
Contact:
Site Public Contact
253-403-3229
research@multicare.org

More Details

NCT ID
NCT02466971
Status
Recruiting
Sponsor
National Cancer Institute (NCI)

Detailed Description

PRIMARY OBJECTIVES:

I. To evaluate the efficacy of the experimental regimen of triapine (3AP), cisplatin, and radiation to increase progression-free survival relative to the standard/control regimen of cisplatin and radiation in women with uterine cervix and vaginal cancer.

SECONDARY OBJECTIVES:

I. To determine the post-therapy 3-month fludeoxyglucose F-18 (18F-FDG) positron emission tomography (PET)/computed tomography (CT) metabolic complete rate of response rate in the cervix and vaginal by treatment arm.

II. To determine overall survival after triapine-cisplatin radio-chemotherapy and cisplatin radio-chemotherapy.

III. To evaluate incidence and severity of hematologic and gastrointestinal (GI) adverse events by radiation modality; image guided intensity modulated radiation therapy (IG-IMRT) versus conventional pelvic radiotherapy.

IV. To summarize and compare differences in acute adverse events (Common Terminology Criteria for Adverse Events [CTCAE], version [v]4.0) by treatment arm and radiation modality.

V. To summarize and compare differences in chronic or late (>= 30-days from off study treatment date) adverse events (CTCAE, v4.0) by treatment arm and by radiation modality.

TERTIARY OBJECTIVES:

I. To determine peripheral blood methemoglobin proportion before and after triapine infusion (optional for Arm 2 patients).

II. To explore whether knowledge-based planning (KBP) can improve IG-IMRT plans compared to plans that would have been delivered without KBP, estimate the resulting toxicity reduction using normal tissue complication probability (NTCP) models, and determine whether KBP should be a requirement for future IG-IMRT protocols.

OUTLINE: Patients are randomized to 1 of 2 treatment arms.

ARM I: Patients receive cisplatin intravenously (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 external beam radiation therapy (EBRT) (either conventional radiation therapy [RT] or intensity modulated radiation therapy [IMRT]) once daily (QD) 5 days a week for 25 fractions followed by low dose rate (LDR) or high dose rate (HDR) brachytherapy according to institution's standards. Treatment continues in the absence of disease progression or unacceptable toxicity.

ARM II: 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.

After completion of study treatment, patients are followed up at 1 and 3 months, every 3 months for 2 years, and then every 6 months for 3 years.

The patient data from NCI #9434 will be merged with NRG-GY006 per the Protocol Analysis Plan.

Notice

Study information shown on this site is derived from ClinicalTrials.gov (a public registry operated by the National Institutes of Health). The listing of studies provided is not certain to be all studies for which you might be eligible. Furthermore, study eligibility requirements can be difficult to understand and may change over time, so it is wise to speak with your medical care provider and individual research study teams when making decisions related to participation.