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

NCT ID: NCT04308837

Last Updated: 2023-11-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 29 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2018-12-03
• Study Completion Date: 2025-08-31

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

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

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.

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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

Carboplatin

Intervention Type: DRUG

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

Dexamethasone

Intervention Type: DRUG

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

Diphenhydramine

Intervention Type: DRUG

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

Famotidine

Intervention Type: DRUG

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

Palonosetron

Intervention Type: DRUG

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

3D conformal or intensity modulated radiotherapy

Intervention Type: 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.

Surgical resection

Intervention Type: PROCEDURE

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

Adjuvant Chemotherapy

Intervention Type: 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)

Interventions

Paclitaxel

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

Intervention Type: DRUG

Carboplatin

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

Intervention Type: DRUG

Dexamethasone

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

Intervention Type: DRUG

Diphenhydramine

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

Intervention Type: DRUG

Famotidine

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

Intervention Type: DRUG

Palonosetron

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

Intervention Type: DRUG

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.

Intervention Type: RADIATION

Surgical resection

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

Intervention Type: PROCEDURE

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)

Intervention Type: RADIATION

Other Intervention Names

IMRT

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Icahn School of Medicine at Mount Sinai

OTHER

Sponsor Role: lead

Responsible Party

Spiros Hiotis

Associate Professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Spiros Hiotis, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Icahn School of Medicine at Mount Sinai

Locations

Mount Sinai West

New York, New York, United States

Site Status: RECRUITING

Mount Sinai St. Luke's

New York, New York, United States

Site Status: RECRUITING

Icahn School of Medicine at Mount Sinai

New York, New York, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Spiros Hiotis, MD, PhD

Role: CONTACT

spiros.hiotis@mountsinai.org

(212) 241-2891

Other Identifiers

GCO 18-1101

Identifier Type: -

Identifier Source: org_study_id