A Phase II Trial of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) With Chemoradiation

A Phase II Trial of Neoadjuvant Laparoscopic Hyperthermic Intraperitoneal Chemotherapy (HIPEC) With Chemoradiation (Carboplatin and Taxol) as First Line Treatment for Patients With Local Regional Advanced Gastric Cancer

Stomach cancer is the fifth most common digestive cancer and third main cause of death from cancer in the world. Modern management of Gastric cancer involves a multi-disciplinary approach involving surgical oncologists, medical oncologists, gastroenterologists and oncological radiologists. The most common clinical approach to Gastric adenocarcinoma is to begin with staging, which usually involves CT scan/ MRI combined with endoscopic US for more accurate T, N staging. Once the patient is deemed to have locally advanced gastric cancer (T3/T4,N0/+), a staging laparoscopy is recommended to rule out obvious or microscopic peritoneal metastatic disease. Additionally, neoadjuvant chemotherapy is initiated and followed by surgery +/- adjuvant radiation and chemotherapy.This protocol involves the addition of neoadjuvant HIPEC at the time of diagnostic laparoscopy as well as neoadjuvant radiation therapy for improved local and systemic control. The goal of this phase II clinical trial is to evaluate the efficacy of a multi-modality approach to treating patients with locally advanced Gastric cancer by incorporating diagnostic laparoscopy with HIPEC, neo-adjuvant chemo-radiotherapy, followed by surgical resection and adjuvant chemotherapy. The trial aims to assess this multi-modality approach in inducing pathological complete response; decreased rates of disease progression during neoadjuvant therapy; and increased overall, disease-free, and peritoneal disease-free survival.

Study Overview

• Status: Recruiting
• Conditions: Stomach Cancer; Gastric Cancer
• Intervention / Treatment: Drug: Paclitaxel; Drug: Carboplatin; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Famotidine; Drug: Palonosetron; Radiation: 3D conformal or intensity modulated radiotherapy; Procedure: Surgical resection; Radiation: Adjuvant Chemotherapy

• Study Type: Interventional
• Enrollment (Estimated): 29
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Spiros Hiotis, MD, PhD; Phone Number: (212) 241-2891; Email: spiros.hiotis@mountsinai.org

Study Locations

• United States
  • New York
    • New York, New York, United States, 10029
      • Recruiting
      • Icahn School of Medicine at Mount Sinai
    • New York, New York, United States, 10019
      • Recruiting
      • Mount Sinai West
    • New York, New York, United States, 10025
      • Recruiting
      • Mount Sinai St. Luke's

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Clinical diagnosis of gastric cancer post endoscopic ultrasound (EUS), staging must be T3/T4
• N0/+, M0. EUS must have been done within 8 weeks of the protocol start.
• Patient must plan to undergo surgical treatment.
• ECOG Scale of Performance Status of 0-2
• Adequate organ and marrow function (leukocytes ≥ 3000/mcl, absolute neutrophil count ≥ 1500, platelets ≥ 100,000/mcl, total bilirubin ≥ 1.5mg/dl (Gilbert's syndrome, then <3.0), AST(SGOT)/ALT(SPGT) ≤ 2.5 X institutional upper limit of normal, creatinine within normal institutional limits)
• Women of child-bearing potential and men must agree to use adequate contraception prior to study entry, for the duration of study participation, and for 90 days following completion of therapy. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.
• Ability to understand and the willingness to sign a written informed consent.

Exclusion Criteria:

• Subjects who have any previous treatment for their cancer.
• Patients with known metastatic disease; this includes patients with clinically apparent or suspected metastasis to sites other than lymph nodes or peritoneal surfaces.
• Subjects with early stage gastric cancer (Stage T1/T2 N0)
• History of allergic reactions attributed to compounds of similar chemical or biological composition to any of the agents being used in this study, including but not limited to: Carboplatin, Taxol, 5-FU, Leucovorin, Mitomycin C.
• Subjects who have received prior radiation to any portion of the abdominal cavity or pelvis are excluded.
• Subjects who have had prior malignancies, except for cured non-melanoma skin cancer, or curatively treated in situ carcinoma of the cervix, or adequately treated malignancies for which there has been no evidence of activity for more than three years.
• Patients must not be pregnant or nursing due to the potential for congenital abnormalities and the potential of this regimen to harm nursing infants.
• Subjects with a condition that may interfere with the subjects' ability to understand the requirements of the study.
• Known HIV, Hepatitis B, or Hepatitis C positive patients.
• Patients with active coronary artery disease (defined as unstable angina or a positive cardiac stress test) will be excluded. Subjects with a history of coronary artery disease may be included if they have had a normal stress test within 30 days of enrollment.
• Patients with restrictive or obstructive pulmonary disease that would limit study compliance or place the patient at unacceptable risk for participation in the study will be excluded.
• Patients with a history of cerebrovascular disease that would limit study compliance or place the patient at unacceptable risk for participation in the study will be excluded.
• Subjects with other concurrent severe medical problems unrelated to the malignancy that would significantly limit full compliance with the study, or places them at an unacceptable risk for participation in the study, will also be excluded.
• Evidence of extensive intraperitoneal adhesions at the time of surgery which prohibits intraperitoneal therapy, as determined by the operating surgeon.
• Patients with any condition that would precluded the ability to deliver appropriate IP therapy.
• Patients with a life expectancy of less than 12 weeks will be excluded from this study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Patients With Local Regional Advanced Gastric Cancer; Patients with local regional advanced gastric cancer after at least 4 weeks post diagnostic laparoscopy and HIPEC, will receive all of the treatments described in the study protocol.

Drug: Paclitaxel; 50 mg/m2 given by intravenous infusion on days 1, 8, 15, 22 and 29.; Drug: Carboplatin; Carboplatin AUC = 2 given by intravenous infusion on days 1, 8, 15, 22 and 29.; Drug: Dexamethasone; All patients receiving Paclitaxel will receive institutional standard premedications, which include Dexamethasone (10 mg IVPB); Drug: Diphenhydramine; All patients receiving Paclitaxel will receive institutional standard premedications, which include diphenhydramine (50mg IVP); Drug: Famotidine; All patients receiving Paclitaxel will receive institutional standard premedications, which include Famotidine (20mg IVPB); Drug: Palonosetron; All patients receiving Paclitaxel will receive institutional standard premedications, which include Palonosetron (0.25mg IVP); Radiation: 3D conformal or intensity modulated radiotherapy; Treatment will be given 5 days per week. Photon beams >6 MV are required. Treatment may be delivered either by a 3D conformal technique or IMRT. IMRT via dynamically moving MLCs, step-and-shoot with a multileaf collimator, Rapid Arc, binary multileaf collimator, and tomotherapy are allowed. Proton therapy is not allowed.; Other Names: IMRT; Procedure: Surgical resection; Surgical resection will constitute subtotal or total gastrectomy (depending on tumor size and location) and D2 lymphadenectomy.; Radiation: Adjuvant Chemotherapy; The patient will begin adjuvant chemotherapy 4-12 weeks after surgery. The adjuvant chemotherapy will consist of FOLFOX every 2 weeks for 6 cycles (i.e. 3 months)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pathological Response	The pathological complete response (the lack of all signs of cancer in tissue samples), at the time of surgical resection. This will be determined using a four-category tumor regression score system that evaluates the response of the cancer cells to the treatment. RECIST - Complete Response (CR), Partial Response (PR) Progressive Disease (PD), and Stable Disease (SD)	at time of surgical resection

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the time from the first dose of study treatment to the date of death (whatever the cause).	6 years
Disease-free Survival	The length of time after treatment ends that the patient survives without any signs or symptoms.	6 years
Peritoneal Disease-free Survival	The length of time after treatment ends that the patient survives without any peritoneal signs or symptoms.	6 years

Collaborators and Investigators

• Sponsor: Icahn School of Medicine at Mount Sinai
• Investigators: Principal Investigator: Spiros Hiotis, MD, PhD, Icahn School of Medicine at Mount Sinai

Study record dates

Study Major Dates

• Study Start (Actual): December 3, 2018
• Primary Completion (Estimated): August 1, 2025
• Study Completion (Estimated): August 1, 2025

Study Registration Dates

• First Submitted: March 12, 2020
• First Submitted That Met QC Criteria: March 12, 2020
• First Posted (Actual): March 16, 2020

Study Record Updates

• Last Update Posted (Estimated): November 14, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Keywords: Chemoradiation; HIPEC; Phase II Trial
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Autonomic Agents; Peripheral Nervous System Agents; Sensory System Agents; Anesthetics; Anti-Inflammatory Agents; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Antineoplastic Agents, Phytogenic; Dermatologic Agents; Serotonin Agents; Serotonin Antagonists; Hypnotics and Sedatives; Anesthetics, Local; Serotonin 5-HT3 Receptor Antagonists; Anti-Ulcer Agents; Anti-Allergic Agents; Sleep Aids, Pharmaceutical; Histamine H1 Antagonists; Histamine Antagonists; Histamine Agents; Antipruritics; Histamine H2 Antagonists; Dexamethasone; Carboplatin; Paclitaxel; Palonosetron; Diphenhydramine; Promethazine; Famotidine
• Other Study ID Numbers: GCO 18-1101

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No