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Advanced Cervical AdenocarcinomaPhase 1NCT02595879

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

A Phase 1 study testing Biospecimen Collection, Brachytherapy and Cisplatin in people with Advanced Cervical Adenocarcinoma and Advanced Cervical Adenosquamous Carcinoma, run by National Cancer Institute (NCI) at 17 sites in United States.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial 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. Read more about this study

Who is it for?
Ages 18 years and older, women only
What is being tested?
Biospecimen Collection, Brachytherapy and Cisplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
21 participants
Where
17 sitesUnited States
Study dates
18 Sep 2019to 29 Apr 2027
Phase
Phase 1

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • Women only
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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
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  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • 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

Trial locations and contacts

17 sites in 1 country.

17 sites in 1 country

United States17 sites

  • University of Michigan Rogel Cancer Center

    Ann Arbor, Michigan, 48109

  • University of Alabama at Birmingham Cancer Center

    Birmingham, Alabama, 35233

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • Wayne State University/Karmanos Cancer Institute

    Detroit, Michigan, 48201

  • University of Kansas Clinical Research Center

    Fairway, Kansas, 66205

  • Weisberg Cancer Treatment Center

    Farmington Hills, Michigan, 48334

  • University of Kansas Cancer Center

    Kansas City, Kansas, 66160

  • University of Kentucky/Markey Cancer Center

    Lexington, Kentucky, 40536

  • Los Angeles General Medical Center

    Los Angeles, California, 90033

  • USC / Norris Comprehensive Cancer Center

    Los Angeles, California, 90033

  • Rutgers Cancer Institute of New Jersey

    New Brunswick, New Jersey, 08903

  • University of Oklahoma Health Sciences Center

    Oklahoma City, Oklahoma, 73104

  • University of Kansas Hospital-Indian Creek Campus

    Overland Park, Kansas, 66211

  • Keck Medical Center of USC Pasadena

    Pasadena, California, 91105

  • UPMC Hillman Cancer Center

    Pittsburgh, Pennsylvania, 15232

  • VCU Massey Comprehensive Cancer Center

    Richmond, Virginia, 23298

  • University of Kansas Hospital-Westwood Cancer Center

    Westwood, Kansas, 66205

Other trials in United States

About this study

Official title: Phase I Dose-Escalation Bioavailability Study of Oral Triapine in Combination With Concurrent Chemoradiation for Locally Advanced Cervical Cancer (LACC) and Vaginal Cancer

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.

Read the detailed description

PRIMARY OBJECTIVES:

  1. 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:

  1. 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:

  1. 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.

Being tested
Biospecimen Collection, Brachytherapy, Cisplatin, Computed Tomography, External Beam Radiation Therapy
Medical subject headings
Uterine Cervical Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Biospecimen CollectionProcedure or surgery

    Also called Biological Sample Collection, Biospecimen Collected, Sample Collection, Specimen Collection

    Undergo collection of blood samples

  • BrachytherapyRadiation

    Also called Brachytherapy, NOS, Internal Radiation, Internal Radiation Brachytherapy, Internal Radiation Therapy

    Undergo LDR brachytherapy

  • CisplatinDrug

    Also called Abiplatin, Blastolem, Briplatin, CDDP

    Given IV

  • Computed TomographyProcedure or surgery

    Also called CAT, CAT Scan, Computed Axial Tomography, Computerized Axial Tomography

    Undergo FDG-PET/CT

  • External Beam Radiation TherapyRadiation

    Also called Definitive Radiation Therapy, EBRT, External Beam Radiation, External Beam Radiotherapy

    Undergo pelvic EBRT

  • Fludeoxyglucose F-18Other

    Also called 18FDG, FDG, Fludeoxyglucose (18F), fludeoxyglucose F 18

    Undergo FDG-PET/CT

  • High-Dose Rate BrachytherapyRadiation

    Also called Brachytherapy, High Dose, HDR, High dose brachytherapy (procedure)

    Undergo HDR brachytherapy

  • Intensity-Modulated Radiation TherapyRadiation

    Also called IMRT, Intensity modulated radiation therapy (procedure), Intensity Modulated RT, Intensity-Modulated Radiotherapy

    Undergo IMRT

  • Magnetic Resonance ImagingProcedure or surgery

    Also called Magnetic Resonance, Magnetic Resonance Imaging (MRI), Magnetic resonance imaging (procedure), Magnetic Resonance Imaging Scan

    Undergo MRI

  • Pharmacological StudyOther

    Correlative studies

  • Positron Emission TomographyProcedure or surgery

    Also called Medical Imaging, Positron Emission Tomography, PET, PET Scan, Positron emission tomography (procedure)

    Undergo FDG-PET/CT

  • TriapineDrug

    Also called 3-aminopyridine-2-carboxaldehyde thiosemicarbazone, 3-AP, 3-Apct, OCX-0191

    Given IV and PO

Study groups in NCT02595879
Study groupRoleWhat they receive
Treatment (triapine, chemoradiation)ExperimentalPatients 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.
Receives: 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

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

    Measured: Up to 5 weeks

  2. 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

    Measured: Up to 5 weeks

  3. Bioavailability of Triapine

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

    Measured: Up to 2 weeks

  4. Cmax

    Maximum concentration

    Measured: Up to 24 hours after dosing

  5. Tmax

    Time to maximum concentration,

    Measured: Up to 24 hours after dosing

  6. AUC

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

    Measured: Up to 24 hours after dosing

  7. Elimination Half-life (t 1/2)

    Measured: Up to 24 hours after dosing

Secondary outcomes (4)

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

    The mCR rate at recommended phase 2 dose, defined as a metabolic complete response on PET/CT will be defined as greater than -66% reduction in tumor FDG uptake at sites of abnormal tumor FDG uptake noted on pre-treatment FDG-PET study (considering normal cardiac or liver blood pool).

    Measured: At 3 months post-treatment

  2. Clinical Overall Response Rate

    Clinical response at the recommended phase 2 dose per RECIST v1.1 Complete Response (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Partial Response (PR): At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression). Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study.

    Measured: 3 months post-treatment

  3. Progression Free Survival (PFS)

    Median number of months that patients survive without disease progression from end of treatment. Per RECIST v1.1, Progressive Disease (PD): At least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progression).

    Measured: Up to 4 years and 2 months from start of treatment

  4. Overall Survival (OS)

    Median number of months that patients remain alive after end of treatment.

    Measured: Up to 4 years and 2 months from start of treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted4 Nov 2015 (estimated)
  2. Study start18 Sep 2019
  3. Primary completion4 Jun 2023
  4. Study completion29 Apr 2027 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
21 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02595879
Sponsor's protocol ID
NCI-2015-01907
Other IDs
NCI-2015-01907, HCC 15-157, UPCI 15-157, 15-157, 9892, 9892, UM1CA186690
Status last verified
Apr 2026
First submitted
3 Nov 2015
Last updated
31 Jul 2026
Data monitoring committee
No
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • 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.

    PubMed 39673591

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