Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal Cancer
NCT ID: NCT02595879
Last Updated: 2025-11-13
Study Results
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View full resultsBasic Information
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ACTIVE_NOT_RECRUITING
PHASE1
21 participants
INTERVENTIONAL
2019-09-18
2026-04-29
Brief Summary
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Detailed Description
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I. To determine the maximum tolerable dose (MTD) and recommended phase II dose (RP2D) of oral triapine when used in combination with cisplatin plus radiation therapy.
II. To determine the oral bioavailability of triapine. III. To describe the pharmacokinetics (PK) of oral and intravenous triapine.
SECONDARY OBJECTIVES:
I. To determine whether the metabolic complete response (mCR) rate of oral triapine in combination with cisplatin chemoradiation using fludeoxyglucose F 18 (18F-FDG)-positron emission tomography (PET)/computed tomography (CT) at post-therapy (3-month) is at least 70%.
II. To determine clinical overall response rate, progression-free survival, and overall survival.
III. To determine the correlation of methemoglobin proportion (%) and triapine pharmacokinetic exposure.
EXPLORATORY OBJECTIVE:
I. To determine whether active human immunodeficiency virus (HIV) antiretroviral therapy impacts the antitumor activity of triapine.
OUTLINE: This is a dose-escalation study of triapine.
Patients undergo pelvic external beam radiation therapy (EBRT) or intensity modulated radiation therapy (IMRT) 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of low dose rate (LDR) brachytherapy in week 6 or 5 fractions of high dose rate (HDR) brachytherapy at week 4 or 5. Patients also receive triapine intravenously (IV) over 120 minutes on day 1 and orally (PO) on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo magnetic resonance imaging (MRI) and FDG-PET/CT during follow-up.
Conditions
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Study Design
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NA
SINGLE_GROUP
TREATMENT
NONE
Study Groups
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Treatment (triapine, chemoradiation)
Patients undergo pelvic EBRT or IMRT 5 days per week for 5 weeks (25 fractions) with a 3-day boost in week 6, and 1 or 2 applications of LDR brachytherapy in week 6 or 5 fractions of HDR brachytherapy at week 4 or 5. Patients also receive triapine IV over 120 minutes on day 1 and PO on days 2-5, 8-12, 15-19, 22-26, and 29-33 within 90 minutes after pelvic irradiation, and cisplatin IV over 60-120 minutes once weekly for 5 weeks (days 2, 9, 16, 23, and 30). Treatment continues in the absence of disease progression or unacceptable toxicity. Patients may receive a 6th cycle of cisplatin IV during the parametrial boost or any make-up radiation treatment in a sixth week of external beam radiotherapy. Patients undergo the collection of blood samples on study and undergo MRI and FDG-PET/CT during follow-up.
Biospecimen Collection
Undergo collection of blood samples
Brachytherapy
Undergo LDR brachytherapy
Cisplatin
Given IV
Computed Tomography
Undergo FDG-PET/CT
External Beam Radiation Therapy
Undergo pelvic EBRT
Fludeoxyglucose F-18
Undergo FDG-PET/CT
High-Dose Rate Brachytherapy
Undergo HDR brachytherapy
Intensity-Modulated Radiation Therapy
Undergo IMRT
Magnetic Resonance Imaging
Undergo MRI
Pharmacological Study
Correlative studies
Positron Emission Tomography
Undergo FDG-PET/CT
Triapine
Given IV and PO
Interventions
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Biospecimen Collection
Undergo collection of blood samples
Brachytherapy
Undergo LDR brachytherapy
Cisplatin
Given IV
Computed Tomography
Undergo FDG-PET/CT
External Beam Radiation Therapy
Undergo pelvic EBRT
Fludeoxyglucose F-18
Undergo FDG-PET/CT
High-Dose Rate Brachytherapy
Undergo HDR brachytherapy
Intensity-Modulated Radiation Therapy
Undergo IMRT
Magnetic Resonance Imaging
Undergo MRI
Pharmacological Study
Correlative studies
Positron Emission Tomography
Undergo FDG-PET/CT
Triapine
Given IV and PO
Other Intervention Names
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Eligibility Criteria
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Inclusion Criteria
* Age \>= 18 years old
* Eastern Cooperative Oncology Group (ECOG) performance status score of 0, 1, or 2
* Life expectancy greater than 6 months
* Absolute neutrophil count (ANC) \>= 1.5 x 10\^9/L
* Platelets \>= 100 x 10\^9/L
* Hemoglobin (Hgb) \>= 10.0 g/dL (blood transfusions to reach this amount are allowed)
* Serum creatinine =\< 1.5 mg/dL to receive weekly cisplatin
* If serum creatinine is between 1.5 and 1.9 mg/dL, patients 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)
* Total serum bilirubin =\< 1.5 x upper limit of normal (ULN) (in patients with known Gilbert syndrome, a total bilirubin =\< 3.0 x ULN, with direct bilirubin =\< 1.5 x ULN)
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x ULN
* Able to take oral medication
* Not pregnant and not breastfeeding; the effects of triapine on the developing human fetus are unknown; for this reason as well as because heterocyclic carboxaldehydethiosemicarbazones and radiation are known to be teratogenic, women of child-bearing potential and men must agree to use two forms of contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation; patient must have documented negative urine pregnancy test must be resulted within 7 days before initiating protocol therapy; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately; 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
* For HIV and hepatitis B/C (HEPB/C):
* HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible for the dose escalation portion of this trial; for those patients who are enrolled in the HIV positive (+) expansion cohort, they must be HIV infected and be on retroviral therapy with an undetectable viral load within 6 months of enrollment
* For patients with evidence of chronic hepatitis B virus (HBV) infection, the HBV viral load must be undetectable on suppressive therapy, if indicated
* Patients with a history of hepatitis C virus (HCV) infection must have been treated and cured; for patients with HCV infection who are currently on treatment, they are eligible if they have an undetectable HCV viral load
* Able to understand and willingness to sign a written informed consent document
Exclusion Criteria
* 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
* Patients receiving any other investigational agents
* Patients with known glucose-6-phosphate dehydrogenase deficiency (G6PD) are excluded due to an inability to administer the antidote for methemoglobinemia, methylene blue; pre-registration testing for G6PD is at the investigator's discretion and is not required for study enrollment
* Patients who are taking any medication associated with methemoglobinemia; medication must be discontinued and must have a washout period of 4 halflives or 4 weeks, whichever is shorter
* History of allergic reactions attributed to compounds of similar chemical or biologic composition to triapine or cisplatin
* 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; or psychiatric illness/social situations that would limit compliance with study requirements
* Patients with uncontrolled diabetes mellitus (fasting blood glucose controlled by medication, =\< 200 mg/dL allowed)
* 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
18 Years
FEMALE
No
Sponsors
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National Cancer Institute (NCI)
NIH
Responsible Party
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Principal Investigators
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Sarah E Taylor
Role: PRINCIPAL_INVESTIGATOR
University of Pittsburgh Cancer Institute LAO
Locations
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University of Alabama at Birmingham Cancer Center
Birmingham, Alabama, United States
Los Angeles General Medical Center
Los Angeles, California, United States
USC / Norris Comprehensive Cancer Center
Los Angeles, California, United States
Keck Medical Center of USC Pasadena
Pasadena, California, United States
University of Kansas Clinical Research Center
Fairway, Kansas, United States
University of Kansas Cancer Center
Kansas City, Kansas, United States
University of Kansas Hospital-Indian Creek Campus
Overland Park, Kansas, United States
University of Kansas Hospital-Westwood Cancer Center
Westwood, Kansas, United States
University of Kentucky/Markey Cancer Center
Lexington, Kentucky, United States
University of Michigan Comprehensive Cancer Center
Ann Arbor, Michigan, United States
Wayne State University/Karmanos Cancer Institute
Detroit, Michigan, United States
Weisberg Cancer Treatment Center
Farmington Hills, Michigan, United States
Rutgers Cancer Institute of New Jersey
New Brunswick, New Jersey, United States
University of Oklahoma Health Sciences Center
Oklahoma City, Oklahoma, United States
University of Pittsburgh Cancer Institute (UPCI)
Pittsburgh, Pennsylvania, United States
University of Virginia Cancer Center
Charlottesville, Virginia, United States
VCU Massey Comprehensive Cancer Center
Richmond, Virginia, United States
Countries
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References
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Taylor SE, Behr S, Cooper KL, Mahdi H, Fabian D, Gallion H, Ueland F, Vargo J, Orr B, Girda E, Courtney-Brooks M, Olawaiye AB, Randall LM, Richardson DL, Sullivan SA, Huang M, Christner SM, Beriwal S, Lin Y, Chauhan A, Chu E, Kohn EC, Kunos C, Ivy SP, Beumer JH. Dose finding, bioavailability, and PK-PD of oral triapine with concurrent chemoradiation for locally advanced cervical cancer and vaginal cancer (ETCTN 9892). Cancer Chemother Pharmacol. 2024 Dec 14;95(1):4. doi: 10.1007/s00280-024-04720-1.
Provided Documents
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Document Type: Study Protocol and Statistical Analysis Plan
Other Identifiers
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NCI-2015-01907
Identifier Type: REGISTRY
Identifier Source: secondary_id
HCC 15-157
Identifier Type: -
Identifier Source: secondary_id
UPCI 15-157
Identifier Type: -
Identifier Source: secondary_id
15-157
Identifier Type: -
Identifier Source: secondary_id
9892
Identifier Type: OTHER
Identifier Source: secondary_id
9892
Identifier Type: OTHER
Identifier Source: secondary_id
NCI-2015-01907
Identifier Type: -
Identifier Source: org_study_id