Neoadjuvant Intra-tumoral RP2 and FLOT in Gastroesophageal Adenocarcinoma

Официальное название

Phase II Study of Neoadjuvant RP2 in Combination With Preoperative Flot for Patients With Stage II or Higher, Non-metastatic Gastroesophageal Adenocarcinoma

Обзор

The research study is being conducted to study whether performing injections of a new treatment, called RP2, directly into stomach and esophagus tumors along with standard chemotherapy (called FLOT) is safe and whether it does a better job of killing cancer before surgery compared to chemotherapy alone.

Подробное описание

This is a single-arm, phase II study using a Simon two-stage optimal design with a 6 patient safety run-in evaluating the addition of intra-tumoral injections of RP2 to standard of care perioperative FLOT for patients with stage II or higher, non-metastatic esophageal, gastroesophageal junction (GEJ), or gastric adenocarcinoma. We hypothesize that the addition of RP2 to perioperative FLOT will be safe and will significantly improve pathologic complete response (pCR) rate compared to the historical weighted average of 12% observed with perioperative FLOT in the ESOPEC trial, MATTERHORN trial, and FLOT4 trial.

Вмешательства

• Биопрепарат RP2
  Upper endoscopy with RP2 intra-tumoral injection of 1 x 10(6) plaque forming units (PFU)/mL for first intra-tumoral injection, up to 10mL of 1x107 PFU/mL of RP2 for subsequent intra-tumoral injections. Injection will occur within 4 days prior of each cycle FLOT.
• Комбинированный продукт 5-Fluorouracil
  5-Fluorouracil as part of the FLOT regimen 2,600mg/m2 intravenous infusion over 24 hours on day 1 of each 14-day cycle for 4 cycles.
• Комбинированный продукт Leucovorin
  Leucovorin as part of the FLOT regimen 200mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.
• Комбинированный продукт Oxaliplatin
  Oxaliplatin as part of the FLOT regimen 85mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.
• Комбинированный продукт Docetaxel
  Docetaxel as part of the FLOT regimen 50mg/m2 intravenous infusion on day 1 of a 14-day cycle for 4 cycles.
• Препарат Pegfilgrastim
  Pegfilgrastim or Filgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.
• Препарат Filgrastim
  Filgrastim or Pegfilgrastim is required on the study and should be administered per the package insert of the commercially obtained drug following each cycle of FLOT for 4 cycles.
• Процедура Surgical Resection of Primary Tumor
  Following 4 cycles of preoperative FLOT with RP2 injections, surgical resection of esophageal, GEJ, or gastric primary tumor per standard of care practice.

Первичные конечные точки

• Pathologic complete response [Срок оценки: Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.]

Вторичные конечные точки (4)

• Adverse event profile [Срок оценки: The adverse event reporting period first RP2 intratumoral injection until 30 days post-surgical resection or 56 days after the last administration of RP2 (if no resection or or consent withdrawal).]
• R0 resection rate [Срок оценки: Assessed after completion of neoadjuvant FLOT and intra-tumoral injections of RP2 and surgical resection. This will typically be in the range of 4-5 months from the time of enrollment.]
• Disease-free Survival (DFS) [Срок оценки: Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.]
• Overall Survival (OS) [Срок оценки: Follow up for this end point may occur for up to 5 years following surgical resection, or data cutoff, whichever comes first.]

Критерии участия

Критерии включения

• Patients must have histologically confirmed and clinically staged T2 or higher or node positive, non-metastatic esophageal, gastroesophageal junction, or gastric adenocarcinoma.
• Patients must have an Eastern Cooperative Oncology Group (ECOG) performance status of 0 - 1.
• Patents must be deemed a surgical candidate by a thoracic surgeon, surgical oncologist, or surgeon who is qualified to perform the appropriate surgical procedure based on patient's primary tumor site.
• Patients must have normal organ and bone marrow function, as defined below, less than or equal to 14 days prior to the initiation of study therapy:

• Absolute neutrophil count (ANC) ≥ 1,500/microliter
• Platelets ≥100,000/microliter
• Total bilirubin ≤ the institutional upper limit of normal (ULN).
• AST and ALT ≤ 2.5 times the institutional ULN
• Serum creatinine ≤ 1.5 times the institutional ULN
• Hemoglobin ≥ 9 g/dL

Критерии исключения

• Has received prior chemotherapy, radiation therapy, or immunotherapy (anti-programmed cell death protein-1 (PD-1), anti-programmed death ligand-1 (PD-L1), or anti-cytotoxic T-lymphocyte associated protein 4 (CTLA-4) for the current malignancy.
• Per the investigator, has contraindications to receiving chemotherapy with FLOT.
• Per the sub-investigator (gastroenterologist) responsible for intra-tumoral injections or the investigator, patient has contraindications to repeated upper endoscopy for intra-tumoral injections. These could include medical conditions that would, per the judgment of the sub-investigator or investigator, inappropriately increase the risk of upper endoscopy.
• Conditions in which anticoagulant therapies cannot be safely stopped in the periprocedural period or patients on warfarin with a target international normalized ratio (INR) ≥ 2.5 that cannot be temporarily reversed to INR ≤ 1.7.
• Active significant herpetic infections or prior complications of Herpes simplex virus-1 (HSV-1) infection (e.g., herpetic keratitis or encephalitis) or requires intermittent or chronic use of systemic (oral or intravenous \[IV\]) antivirals with known antiherpetic activity (e.g., acyclovir). Note: Patients with sporadic cold sores may be enrolled as long as no active cold sores are present at the time of first dose of study treatment.
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacille Calmette-Guérin (BCG), and typhoid vaccine. Note: Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed, however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed. Available COVID-19 vaccines do not contain live virus and are allowed.
• Has a condition requiring systemic treatment with corticosteroids (>10mg/day prednisone equivalents) or other immunosuppressive medications within 14 days of first study treatment administration.

• Inhaled or topical steroids and adrenal replacement doses ≤ 10mg/day of prednisone equivalents are permitted.
• Prior organ transplantation including allogeneic stem-cell transplantation.
• Has a previous or concurrent malignancy. Exceptions include:

• Non-melanoma skin cancer, in situ cervical cancer, superficial bladder cancer, or breast cancer in situ OR
• Prior malignancy has been completely excised or removed and patient has been continuously disease free for > 5-years
• Has a positive test result for hepatitis B virus surface antigen (HBsAg) or hepatitis C virus ribonucleic acid (HCV RNA) indicating acute or chronic infection with hepatitis B or hepatitis C. Testing will be performed as part of screening on the study.

• Patients with a known history of hepatitis B or hepatitis C that have been effectively treated (with negative HBsAg and HCV RNA) will be eligible for enrollment on this criterion.
• Has a known history of human immunodeficiency virus (HIV) with detectable viral load. HIV testing will not be performed as part of screening for the study.

• Patients with known HIV infection with an undetectable viral load and who are on a stable highly active antiviral regimen per the investigator's assessment will eligible to enroll.
• Has a psychiatric illness, substance use, or other social conditions that, in the judgment of the investigator, would limit compliance with study requirements.

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

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Лечение

Центры проведения

США · 1 центр

• Abramson Cancer Center at the University of Pennsylvania — Philadelphia

Идентификаторы

NCT: NCT07059611 · UPCC 06225

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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