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

  • STATUS
    Recruiting
  • participants needed
    76
  • sponsor
    National Cancer Institute (NCI)
Updated on 6 February 2023
ct scan
estimated creatinine clearance
cancer
absolute neutrophil count
carcinoma
direct bilirubin
x-rays
metastasis
adenosquamous carcinoma
tumor cells
fludeoxyglucose
brachytherapy
external beam radiation therapy
adenocarcinoma
pet/ct scan
triapine
uterine cervix
cervical carcinoma
intensity-modulated radiation therapy
radiation brachytherapy
carcinoma of cervix

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.

Description

PRIMARY OBJECTIVES:

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 days 1, 2, 8, and 9 and undergo magnetic resonance imaging (MRI) and FDG-PET/CT at 3 months.

After completion of study treatment, patients are followed up for 3 months.

Details
Condition 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 IB2 Cervical Cancer AJCC v6 and v7, Stage II Cervical Cancer AJCC v7, 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
Treatment laboratory biomarker analysis, cisplatin, brachytherapy, computed tomography, magnetic resonance imaging, positron emission tomography, pharmacological study, Fludeoxyglucose F-18, intensity-modulated radiation therapy, Internal Radiation Therapy, biospecimen collection, external beam radiation therapy, Triapine, High-Dose Rate Brachytherapy
Clinical Study IdentifierNCT02595879
SponsorNational Cancer Institute (NCI)
Last Modified on6 February 2023

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