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
Overview
- Phase
- Phase 2
- Intervention
- Paclitaxel
- Conditions
- Gastric Cancer
- Sponsor
- Icahn School of Medicine at Mount Sinai
- Enrollment
- 29
- Locations
- 3
- Primary Endpoint
- Pathological Response
- Status
- Recruiting
- Last Updated
- 2 years ago
Overview
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.
Investigators
Spiros Hiotis
Associate Professor
Icahn School of Medicine at Mount Sinai
Eligibility Criteria
Inclusion Criteria
- •Clinical diagnosis of gastric cancer post endoscopic ultrasound (EUS), staging must be T3/T4
- •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.
Arms & Interventions
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.
Intervention: Paclitaxel
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.
Intervention: Carboplatin
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.
Intervention: Dexamethasone
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.
Intervention: Diphenhydramine
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.
Intervention: Famotidine
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.
Intervention: Palonosetron
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.
Intervention: 3D conformal or intensity modulated radiotherapy
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.
Intervention: Surgical resection
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.
Intervention: Adjuvant Chemotherapy
Outcomes
Primary Outcomes
Pathological Response
Time Frame: at time of surgical resection
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)
Secondary Outcomes
- Disease-free Survival(6 years)
- Peritoneal Disease-free Survival(6 years)
- Overall Survival (OS)(6 years)