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

NCT04308837 | Unknown Phase 2 FDA Drug

• 1 other identifier: GCO 18-1101
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Gastric Cancer; Stomach Cancer

Keywords

Phase II Trial; HIPEC; Chemoradiation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (3)

• Overall Survival (OS)

  6 years

• Disease-free Survival

  6 years

• Peritoneal Disease-free Survival

  6 years

Study Arms (1)

Patients With Local Regional Advanced Gastric Cancer

EXPERIMENTAL

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; Drug: Carboplatin; Drug: Dexamethasone; Drug: Diphenhydramine; Drug: Famotidine; Drug: Palonosetron; Radiation: 3D conformal or intensity modulated radiotherapy; Procedure: Surgical resection; Radiation: Adjuvant Chemotherapy

Interventions

Paclitaxel DRUG

50 mg/m2 given by intravenous infusion on days 1, 8, 15, 22 and 29.

Patients With Local Regional Advanced Gastric Cancer

Carboplatin DRUG

Carboplatin AUC = 2 given by intravenous infusion on days 1, 8, 15, 22 and 29.

Patients With Local Regional Advanced Gastric Cancer

Dexamethasone DRUG

All patients receiving Paclitaxel will receive institutional standard premedications, which include Dexamethasone (10 mg IVPB)

Patients With Local Regional Advanced Gastric Cancer

Diphenhydramine DRUG

All patients receiving Paclitaxel will receive institutional standard premedications, which include diphenhydramine (50mg IVP)

Patients With Local Regional Advanced Gastric Cancer

Famotidine DRUG

All patients receiving Paclitaxel will receive institutional standard premedications, which include Famotidine (20mg IVPB)

Patients With Local Regional Advanced Gastric Cancer

Palonosetron DRUG

All patients receiving Paclitaxel will receive institutional standard premedications, which include Palonosetron (0.25mg IVP)

Patients With Local Regional Advanced Gastric Cancer

3D conformal or intensity modulated radiotherapy RADIATION

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.

Also known as: IMRT

Patients With Local Regional Advanced Gastric Cancer

Surgical resection PROCEDURE

Surgical resection will constitute subtotal or total gastrectomy (depending on tumor size and location) and D2 lymphadenectomy.

Patients With Local Regional Advanced Gastric Cancer

Adjuvant Chemotherapy RADIATION

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)

Patients With Local Regional Advanced Gastric Cancer

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Icahn School of Medicine at Mount Sinai: lead

Study Sites (3)

Mount Sinai West

New York, New York, 10019, United States

RECRUITING

Mount Sinai St. Luke's

New York, New York, 10025, United States

RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, 10029, United States

RECRUITING

MeSH Terms

Conditions

Stomach Neoplasms

Interventions

Paclitaxel; Carboplatin; Dexamethasone; Diphenhydramine; Famotidine; Palonosetron; Radiotherapy, Conformal; Radiotherapy, Intensity-Modulated; Chemotherapy, Adjuvant

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Coordination Complexes; Pregnadienetriols; Pregnadienes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Steroids, Fluorinated; Ethylamines; Amines; Benzhydryl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Thiazoles; Sulfur Compounds; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Quinuclidines; Heterocyclic Compounds, Bridged-Ring; Isoquinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Radiotherapy, Computer-Assisted; Radiotherapy; Therapeutics; Combined Modality Therapy; Drug Therapy

Study Officials

• Spiros Hiotis, MD, PhD

  Icahn School of Medicine at Mount Sinai

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Spiros Hiotis, MD, PhD

CONTACT

(212) 241-2891; spiros.hiotis@mountsinai.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: The study design involves a single arm of patients that will all receive the same treatment.

Study Record Dates

• First Submitted: March 12, 2020
• First Posted: March 16, 2020
• Study Start: December 3, 2018
• Primary Completion: August 1, 2025
• Study Completion: August 1, 2025
• Last Updated: November 14, 2023

Record last verified: 2023-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (3)