Triapine With Chemotherapy and Radiation Therapy in Treating Patients With IB2-IVA Cervical or Vaginal Cancer

NCT02595879 | Active Not Recruiting Phase 1 Results FDA Drug

• 6 other identifiers: NCI-2015-01907HCC 15-157UPCI 15-15715-1579892UM1CA186690
• Study Type: interventional
• Target: 21
• Locations: 1 country
• Sites: 17

Brief Summary

This phase I trial studies the side effects and best dose of triapine when given with radiation therapy and cisplatin in treating patients with stage IB2-IVA cervical or vaginal cancer. Triapine may stop the growth of cancer cells by blocking an enzyme needed for cell growth. Cisplatin is a drug used in chemotherapy that kills cancer cells by damaging their deoxyribonucleic acid (DNA) and stopping them from dividing. Radiation therapy uses high-energy x-rays to kill tumor cells and shrink tumors. Adding triapine to standard treatment with cisplatin and radiation therapy may kill more cancer cells.

Conditions

Stage II Vaginal Cancer AJCC v6 and v7; Stage III Vaginal Cancer AJCC v6 and v7; Stage IIIB Cervical Cancer AJCC v6 and v7; Stage IVA Cervical Cancer AJCC v6 and v7; Stage IVA Vaginal Cancer AJCC v6 and v7; Stage IB2 Cervical Cancer AJCC v6 and v7; Advanced Cervical Adenocarcinoma; Advanced Cervical Adenosquamous Carcinoma; Advanced Cervical Squamous Cell Carcinoma; Advanced Vaginal Adenocarcinoma; Advanced Vaginal Adenosquamous Carcinoma; Advanced Vaginal Squamous Cell Carcinoma; Stage II Cervical Cancer AJCC v7

Outcome Measures

Primary Outcomes (7)

• Maximum Tolerated Dose (MTD)

  The MTD was determined following a standard 3+3 design is as follows: Escalation at 0/3 DLTs, dose-reduction if \>1/3 DLT, and expansion to 6 if 1/3 DLTs. DLT is defined as the severe toxicity event that leads to the termination of the treatment as defined in section 5.5. The highest dose level where \<2/6 DLTs are observed will be declared MTD

  Up to 5 weeks

• Number of Patients Who Experienced a DLT

  Number of patients that experienced a DLT, evaluated using the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) v4.0. DLTs are defined as the following adverse events if considered at least "possibly related" to a component of the study therapy and which occur from the start of treatment until completion of EBRT, prior to initiation of brachytherapy (i.e. the first 5 weeks if no treatments are missed): Any nausea, vomiting, diarrhea and elevation of serum creatinine level Grade 3 toxicity not resolved with maximal intervention to Grade 0-2 over 7 days (except alopecia and fatigue); Any nausea, vomiting, diarrhea and elevation of serum creatinine level Grade 4 toxicity; Any other non-hematologic toxicity ≥Grade 3; Any hematologic toxicity of ≥ Grade 4; Grade ≥3 dyspnea; Inability to deliver at least 20 of the scheduled 25 administrations of triapine at the planned dose, allowing for 2 weeks to make up missed radiation days. Inability to deliver

  Up to 5 weeks

• Bioavailability of Triapine

  The oral bioavailability of the oral form of the triapine will be measured as a numeric value using mass spectrophotometry.

  Up to 2 weeks

• Cmax

  Maximum concentration

  Up to 24 hours after dosing

• Tmax

  Time to maximum concentration,

  Up to 24 hours after dosing

• AUC

  Area Under the Concentration-Time Curve (AUC 0-last)

  Up to 24 hours after dosing

• Elimination Half-life (t 1/2)

  Up to 24 hours after dosing

Secondary Outcomes (4)

• Fludeoxyglucose F18-Positron Emission Tomography Computed Tomography Metabolic Complete Response (mCR) Rate

  At 3 months post-treatment

• Clinical Overall Response Rate

  3 months post-treatment

• Progression Free Survival (PFS)

  Up to 4 years and 2 months from start of treatment

• Overall Survival (OS)

  Up to 4 years and 2 months from start of treatment

Study Arms (1)

Treatment (triapine, chemoradiation)

EXPERIMENTAL

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.

Procedure: Biospecimen Collection; Radiation: Brachytherapy; Drug: Cisplatin; Procedure: Computed Tomography; Radiation: External Beam Radiation Therapy; Other: Fludeoxyglucose F-18; Radiation: High-Dose Rate Brachytherapy; Radiation: Intensity-Modulated Radiation Therapy; Procedure: Magnetic Resonance Imaging; Other: Pharmacological Study; Procedure: Positron Emission Tomography; Drug: Triapine

Interventions

Biospecimen Collection PROCEDURE

Undergo collection of blood samples

Also known as: Biological Sample Collection, Biospecimen Collected, Specimen Collection

Treatment (triapine, chemoradiation)

Brachytherapy RADIATION

Undergo LDR brachytherapy

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

Treatment (triapine, chemoradiation)

Cisplatin DRUG

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

Treatment (triapine, chemoradiation)

Computed Tomography PROCEDURE

Undergo FDG-PET/CT

Also known as: CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography, Computerized axial tomography (procedure), Computerized Tomography, Computerized Tomography (CT) scan, CT, CT Scan, Diagnostic CAT Scan, Diagnostic CAT Scan Service Type, tomography

Treatment (triapine, chemoradiation)

External Beam Radiation Therapy RADIATION

Undergo pelvic 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

Treatment (triapine, chemoradiation)

Fludeoxyglucose F-18 OTHER

Undergo FDG-PET/CT

Also known as: 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18, Fludeoxyglucose F18, Fluorine-18 2-Fluoro-2-deoxy-D-Glucose, Fluorodeoxyglucose F18

Treatment (triapine, chemoradiation)

High-Dose Rate Brachytherapy RADIATION

Undergo HDR brachytherapy

Also known as: Brachytherapy, High Dose, HDR, High dose brachytherapy (procedure)

Treatment (triapine, chemoradiation)

Intensity-Modulated Radiation Therapy RADIATION

Undergo IMRT

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

Treatment (triapine, chemoradiation)

Magnetic Resonance Imaging PROCEDURE

Undergo MRI

Also known as: Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan, Medical Imaging, Magnetic Resonance / Nuclear Magnetic Resonance, MR, MR Imaging, MRI, MRI Scan, MRIs, NMR Imaging, NMRI, Nuclear Magnetic Resonance Imaging, sMRI, Structural MRI

Treatment (triapine, chemoradiation)

Pharmacological Study OTHER

Correlative studies

Treatment (triapine, chemoradiation)

Positron Emission Tomography PROCEDURE

Undergo FDG-PET/CT

Also known as: Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure), Positron Emission Tomography Scan, Positron-Emission Tomography, PT

Treatment (triapine, chemoradiation)

Triapine DRUG

Given IV and PO

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

Treatment (triapine, chemoradiation)

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patient has a new, untreated histologic diagnosis of stage IB2 (\> 5 cm), II, IIIB, IIIC 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 lymph node metastasis will be based on pre-therapy 18F-FDG PET/CT; the patient must be able to tolerate imaging requirements of an 18F-FDG PET/CT scan
• 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

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (17)

University of Alabama at Birmingham Cancer Center

Birmingham, Alabama, 35233, United States

Location

Los Angeles General Medical Center

Los Angeles, California, 90033, United States

Location

USC / Norris Comprehensive Cancer Center

Los Angeles, California, 90033, United States

Location

Keck Medical Center of USC Pasadena

Pasadena, California, 91105, United States

Location

University of Kansas Clinical Research Center

Fairway, Kansas, 66205, United States

Location

University of Kansas Cancer Center

Kansas City, Kansas, 66160, United States

Location

University of Kansas Hospital-Indian Creek Campus

Overland Park, Kansas, 66211, United States

Location

University of Kansas Hospital-Westwood Cancer Center

Westwood, Kansas, 66205, United States

Location

University of Kentucky/Markey Cancer Center

Lexington, Kentucky, 40536, United States

Location

University of Michigan Rogel Cancer Center

Ann Arbor, Michigan, 48109, United States

Location

Wayne State University/Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Weisberg Cancer Treatment Center

Farmington Hills, Michigan, 48334, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

University of Oklahoma Health Sciences Center

Oklahoma City, Oklahoma, 73104, United States

Location

University of Pittsburgh Cancer Institute (UPCI)

Pittsburgh, Pennsylvania, 15232, United States

Location

University of Virginia Cancer Center

Charlottesville, Virginia, 22908, United States

Location

VCU Massey Comprehensive Cancer Center

Richmond, Virginia, 23298, United States

Location

Related Publications (1)

• 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.

  PMID: 39673591 DERIVED

MeSH Terms

Conditions

Uterine Cervical Neoplasms

Interventions

Specimen Handling; Brachytherapy; Cisplatin; 1,2-diaminocyclohexaneplatinum II citrate; Platinum; Congresses as Topic; Radiation; Fluorodeoxyglucose F18; Radiotherapy, Intensity-Modulated; Magnetic Resonance Spectroscopy; 3-aminopyridine-2-carboxaldehyde thiosemicarbazone

Condition Hierarchy (Ancestors)

Uterine Neoplasms; Genital Neoplasms, Female; Urogenital Neoplasms; Neoplasms by Site; Neoplasms; Uterine Cervical Diseases; Uterine Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases

Intervention Hierarchy (Ancestors)

Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Investigative Techniques; Radiotherapy; Therapeutics; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Metals, Heavy; Elements; Transition Elements; Metals; Organizations; Health Care Economics and Organizations; Physical Phenomena; Deoxyglucose; Deoxy Sugars; Carbohydrates; Radiotherapy, Conformal; Radiotherapy, Computer-Assisted; Spectrum Analysis; Chemistry Techniques, Analytical

Results Point of Contact

• Title: Barbara Stadterman, MPH, CCRP
• Organization: UPMC Hillman Cancer Center

stadtermanbm@upmc.edu

4126475554

Study Officials

• Sarah E Taylor

  University of Pittsburgh Cancer Institute LAO

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 3, 2015
• First Posted: November 4, 2015
• Study Start: September 18, 2019
• Primary Completion: June 4, 2023
• Study Completion: April 29, 2026
• Last Updated: April 29, 2026
• Results First Posted: October 16, 2024

Record last verified: 2025-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (17)