Testing the Addition of a New Anti-Cancer Drug, Triapine, to the Usual Chemotherapy Treatment (Cisplatin) During Radiation Therapy for Advanced-stage Cervical and Vaginal Cancers

Titre officiel

A Randomized Phase III Trial of Radiation Therapy and Cisplatin Alone or in Combination With Intravenous Triapine in Women With Newly Diagnosed Bulky Stage IB2, Stage II, IIIB, or IVA Cancer of the Uterine Cervix or Stage II-IVA Vaginal Cancer

Sommaire:

Cette étude de phase III menée à répartition aléatoire porte sur la comparaison de l’efficacité de la radiothérapie et de l’association de cisplatine et de triapine à celle d’une radiothérapie classique associée au cisplatine seul auprès de patients ayant récemment reçu un diagnostic de cancer du col de l’utérus de stade IB2, II ou IIIB-IVA ou de cancer du vagin de stade II-IVA. La radiothérapie administre des protons à haute énergie afin de tuer les cellules tumorales et de réduire la taille des tumeurs. Les médicaments utilisés en chimiothérapie, comme le cisplatine, agissent de différentes manières pour stopper la croissance des cellules tumorales, soit en tuant les cellules, soit en les empêchant de se diviser ou de se propager. Le triapine pourrait stopper la croissance des cellules tumorales en bloquant certaines enzymes nécessaires à la croissance cellulaire. On ne sait pas encore si la radiothérapie et l’administration de cisplatine sont plus efficaces en association avec l’administration de triapine pour traiter le cancer du col de l’utérus ou du vagin.

Description de l'essai

Primary Outcome:

  • Overall survival (OS)
Secondary Outcome:
  • Progression-free survival (PFS)
  • Metabolic complete response (mCR)
  • Incidence of acute adverse events
  • Treatment compliance (amount of radiation, cisplatin and triapine administered, incidence and duration of treatment delays, reason for delays, and reason why off study therapy)
  • Incidence of hematologic and gastrointestinal (GI) adverse events
  • Incidence of chronic or late adverse events
PRIMARY OBJECTIVE:
  • To evaluate the efficacy of the experimental regimen of triapine (3AP), cisplatin, and radiation to increase overall survival relative to the standard/control regimen of cisplatin and radiation in women with uterine cervix or vaginal cancer.
SECONDARY OBJECTIVE:
  • To determine the relative progression-free survival impact of triapine-cisplatin radio-chemotherapy and cisplatin radio-chemotherapy.
TERTIARY OBJECTIVES:
  • 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. (05/30/2017)
  • To summarize and compare differences in acute adverse events (Common Terminology Criteria for Adverse Events [CTCAE], version [v]4.0) by treatment arm and by radiation modality. (05/30/2017)
  • 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. (05/30/2017)
  • To determine peripheral blood methemoglobin proportion before and after triapine infusion (optional for Arm 2 patients).V. 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.
  • To determine the post-therapy 3-month fludeoxyglucose F-18 (18F-FDG) PET/CT metabolic complete response rate by treatment arm VII. To compare acute toxicity and chemotherapy delivery for atlas-based IG-IMRT vs. positron emission tomography (PET)/computed tomography (CT)-based IG-IMRT vs. conventional radiation therapy (RT), and assess the impact of treatment on changes in hematopoietic compensatory response.
  • To develop and validate machine learning and radiomics techniques for dose accumulation, automated treatment planning, and prediction of treatment response.
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 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.

Voir cet essai sur ClinicalTrials.gov

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