Flat Dose vs. Weight-based IP Chemotherapy for CRS/HIPEC

Официальное название

A Randomized Phase 2 Trial of Flat Dose vs. Weight-based Dose of Intra-peritoneal (IP) Chemotherapy for Patients Undergoing Cytoreductive Surgery and Heated Intra-peritoneal Chemotherapy (CRS/HIPEC) for Advanced Gastrointestinal Malignancy

Обзор

Peritoneal carcinomatosis from advanced gastro-intestinal malignancy has historically been associated with poor overall survival (≤ 12 months) with few treatment options. Cytoreductive surgery (CRS), which involves removal of all macroscopic tumor nodules, combined with direct administration of heated intra-peritoneal (IP) chemotherapy (HIPEC) to the affected peritoneal surfaces, has been shown to be an effective treatment option that extends overall survival among certain cases of peritoneal carcinomatosis. IP chemotherapy allows delivery of a high dose of cytostatic drug directly onto the peritoneal surfaces at risk for microscopic residual disease while systemic exposure remains limited. Additionally, hyperthermia is known to enhance the cytotoxicity of several agents (including Mitomycin C) and improves the depth of peritoneal penetration. This trial will be a randomized phase 2 comparison of flat dose versus weight-based dose Mitomycin C. The hypothesis of this study is that HIPEC weight-based dosing may result in similarly effective peritoneal Mitomycin C concentrations with less systemic absorption and potential systemic toxicity, compared with the HIPEC flat dosing approach in patients undergoing CRS/HIPEC.

Вмешательства

• Препарат Mitomycin C, flat dose 40 mg
  Mitomycin C will be delivered as heated intraperitoneal chemotherapy (HIPEC) in two flat doses. Dose 1 will be 30mg at minute 0 and dose 2 will be 10 mg at minute 45.
• Препарат Mitomycin C, weight-based dose 12.5 mg/m2
  Mitomycin C will be delivered as heated intraperitoneal chemotherapy (HIPEC) in two weight-based doses of 9.5 mg/m2 at minute 0 and 3 mg/m2 at minute 45.

Первичные конечные точки

• Area Under the Curve (AUC) - Pharmacokinetics [Срок оценки: Approximately 20 hours]
• Drug Clearance (CL) - Pharmacokinetics [Срок оценки: Approximately 20 hours]
• Drug Half-Life (T1/2) - Pharmacokinetics [Срок оценки: Approximately 20 hours]

Критерии участия

Критерии включения

• Patients diagnosed with one of the following: low-grade appendiceal mucinous neoplasm, pseudomyxoma peritonei, appendiceal cancer with peritoneal carcinomatosis, colorectal cancer with peritoneal carcinomatosis
• ECOG performance status < 3
• Candidate for grossly complete cytoreductive surgery
• Life expectancy greater than 3 months
• Adequate organ and marrow function
• Ability to understand and the willingness to sign a written informed consent document

Критерии исключения

• Any extra-abdominal metastases
• Untreated lung metastases
• Liver metastases not amenable to resection or ablation
• Known brain metastases
• Chemotherapy or radiotherapy within 4 weeks prior to entering the study
• Presence of residual significant adverse events attributed to prior cancer treatment
• Currently receiving any other investigational therapeutic agents
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to Mitomycin C.
• Pregnant or breast-feeding women
• Uncontrolled ongoing illness

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 2 центра

• University of Kentucky — Lexington
• University of Vermont Medical Center — Burlington

Публикации

• McDonald HG, Cassim EB, Harper MM, Burke EE, Marcinkowski EF, Cavnar MJ, Pandalai PK, Kim J. The Development of Investigator-Initiated Clinical Trials in Surgical Oncology. Surg Oncol Clin N Am. 2023 Jan;32(1):13-25. doi: 10.1016/j.soc.2022.07.003. Epub 2022 Nov 3. PMID 36410913

Идентификаторы

NCT: NCT04779554 · MCC-20-GI-115

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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