Heated Intraperitoneal Chemotherapy and Gastrectomy for Gastric Cancer With Positive Peritoneal Cytology

Phase II Trial of Heated Intraperitoneal Chemotherapy and Gastrectomy for Gastric Cancer With Positive Peritoneal Cytology

Background:

- Gastric cancer is a common and serious cancer. Standard treatment is chemotherapy drugs. Researchers want to see if a new treatment helps. It is surgical removal of the cancer and heated chemotherapy delivered to the abdominal cavity called Hyperthermic intraperitoneal chemotherapy (HIPEC).

Objective:

- To test if surgical removal of tumors plus heated intraperitoneal chemotherapy can improve survival in people with gastric cancers.

Eligibility:

- People ages 18 and older with gastric cancer who can have most tumors surgically removed

Design:

• Participants will be screened with:
• Medical history
• Physical exam
• Blood, urine, and heart tests
• Scans
• Tissue sample from previous surgery
• Endoscopy with biopsy: A tube with a camera goes through the mouth and into the stomach. It and takes a sample of stomach tissue. Participants may get medicine to make them drowsy.
• Laparoscopy: Small cuts are made in the abdomen. A thin tube with a light and camera is inserted into the abdomen. Participants sleep through the procedure.

Participants will stay in the hospital. They will have:

• Surgery to remove as many tumors as possible.
• HIPEC for 60 minutes: Two thin tubes are put into the abdomen. Two chemotherapy drugs are given through one tube. They are drained out through another at a temperature a few degrees above normal body temperature. Another drug is given in a vein.
• Recovery for 7-21 days: Participants will have tubes in their stomach and bladder and intravenous (IVs) for a few days. They will get pain medicine, IV fluids, antibiotics, and blood transfusions as needed.
• Participants will have visits every few months for 3 years, then one a year. Visits include physical exam, blood tests, and scans. They also include dietary assessment and questions.

Study Overview

• Status: Completed
• Conditions: Gastric Cancer; Gastric Adenocarcinoma; Esophagogastric Junction
• Intervention / Treatment: Drug: Sodium Thiosulfate; Procedure: Surgery; Drug: Cisplatin; Drug: Mitomycin C; Procedure: Tumor Biopsy; Diagnostic test: CT C/A/P; Diagnostic test: PET-CT; Diagnostic test: MRI; Diagnostic test: EKG

Detailed Description

Background:

• An estimated 24,590 cases of gastric adenocarcinoma are diagnosed annually in the United States (U.S.).
• The peritoneal surface is a site of metastasis found often at time of diagnosis and is a common (40%) site of recurrence.
• Laparoscopy with peritoneal lavage and cytopathologic analysis is a staging modality that can identify a subset of patients with microscopic peritoneal metastasis prior to consideration for definitive surgical therapy.
• Intraperitoneal chemotherapy has been employed in advanced gastric cancers and as an adjuvant with an associated improvement in survival in systematic reviews.

Objectives:

- Determine the overall survival in patients with cytology-positive gastric cancer treated with Hyperthermic intraperitoneal chemotherapy (HIPEC) and gastrectomy.

Eligibility:

• Histologically confirmed adenocarcinoma of the stomach.
• Cytopathologic evidence of peritoneal carcinomatosis.
• Medically fit for systemic chemotherapy, HIPEC and gastrectomy.

Design:

- Single arm, Phase II study of HIPEC and gastrectomy.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 2

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Bethesda, Maryland, United States, 20892
      • National Institutes of Health Clinical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

• INCLUSION CRITERIA:
• Patients must have histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction (Siewert I-III) adenocarcinoma confirmed by the Laboratory of Pathology, national Cancer Institute (NCI).
• Must have received systemic chemotherapy, minimum 3 months or maximum 6 months, prior to enrollment
• Systemic therapy should consist of at least fluoropyrimidine-based and/or platinum-based chemotherapy
• Trastuzumab may be added for human epidermal growth factor receptor 2 (HER2)-neu over-expressing cancers as clinically indicated
• Last dose of chemotherapy within 8 weeks of enrollment with recovery to Grade 1 from chemotherapy-related toxicities
• Documentation of chemotherapy administration must be obtained
• Subradiographic and/or cytopathologic evidence of peritoneal carcinomatosis found at staging laparoscopy.
• Documentation of cytopathologic diagnosis of malignant peritoneal cytology in the absence of disseminated peritoneal disease must be obtained. If cytologic analysis reveals atypical cells of undetermined significance, a repeat lavage with cytopathologic analysis will be performed and must demonstrate evidence of malignancy.
• Limited peritoneal involvement found at staging laparoscopy or on final pathology that is deemed completely resectable is permitted
• Age >18 years.
• Eastern Cooperative Oncology Group (ECOG) performance status <2
• Patients must have normal organ and marrow function as defined below:
• hemoglobin > 8.0 g/dL
• absolute neutrophil count greater than or equal to 1,000/mcL
• platelets greater than or equal to100,000/mcL
• total bilirubin within normal institutional limits
• Aspartate aminotransferase (AST)Serum glutamic-oxaloacetic transaminase (SGOT)/Alanine aminotransferase (ALT)Serum glutamic-pyruvic transaminase (SGPT) less than or equal to 2.5 X institutional upper limit of normal
• creatinine < 1.5 mg/dl
• estimated glomerular filtration rate (GFR) (creatinine clearance) greater than or equal to 60 mL/min/1.73 m^2.
• Physiologically able to undergo heated intraperitoneal chemotherapy (HIPEC) and gastrectomy
• No history of malignancy within 2 years of enrollment except for basal cell carcinoma of the skin, squamous cell skin cancer or carcinoma in situ of the cervix.
• Ability of subject to understand and the willingness to sign a written informed consent document
• Previous exploratory laparotomy or laparoscopy with tissue biopsy or peritoneal lavage is permitted.
• Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while she or her partner is participating in this study, she should inform her treating physician immediately
• Subjects must agree to co-enrollment on the tissue collection protocol 13C0176, Tumor, Normal Tissue and Specimens from Patients Undergoing Evaluation or Surgical Resection of Solid Tumors.

EXCLUSION CRITERIA:

• Patients who are receiving any investigational agents
• Disseminated extra-peritoneal or solid organ metastases

• Includes carcinomatosis associated with clinically or radiographically evident ascites (greater than 500cc)

  --Excludes greater omentum and ovarian metastases

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
• Pregnant women are excluded from this study because HIPEC and gastrectomy have not been studied in pregnant women and has the potential for teratogenic or abortifacient effects. Because there is an unknown but potential risk for adverse events in nursing infant's secondary to treatment of the mother with HIPEC and gastrectomy, breastfeeding should be discontinued if the mother is treated on this study.
• Human immunodeficiency virus (HIV)-positive patients may be considered for this study only after consultation with a National Institute of Allergy and Infectious Diseases (NIAID) physician.

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: Heated Intraperitoneal Chemotherapy (HIPEC) for Gastric Cancer; Heated Intraperitoneal Chemotherapy (HIPEC) with gastrectomy

Drug: Sodium Thiosulfate; Sodium thiosulfate will be administered by continuous intravenous infusion starting immediately prior to the chemotherapy perfusion and continuing for a total of 12 hours.; Other Names: Sodium Hyposulfite; Sodium Thiosulfate Anhydrous; Sodium Thiosulfate Crystal; Prismatic Rice; Procedure: Surgery; Heated Intraperitoneal Chemotherapy (HIPEC) with gastrectomy using cisplatin, mitomycin C and sodium thiosulfate; Drug: Cisplatin; Cisplatin (90 mg/m^2) will be administered via circuit to the peritoneal cavity; Other Names: Platinol; Drug: Mitomycin C; Mitomycin C 10 mg/m^2 will be administered via circuit to the peritoneal cavity; Other Names: Mutamycin; Jelmyto; Mitosol; Procedure: Tumor Biopsy; At screening, baseline (if not done at screening) and operation (as clinically indicated).; Diagnostic test: CT C/A/P; At screening, baseline (if not done at screening), post op care, post-discharge visits/follow-up, semi-annual follow-up and annual follow-up.; Other Names: Computed Tomography of the chest, abdomen and pelvis; Diagnostic test: PET-CT; At screening, baseline (if not done at screening), post op care, post-discharge visits/follow-up, semi-annual follow-up and annual follow-up.; Other Names: Positron emission tomography - computed tomography; Diagnostic test: MRI; If computed tomography (CT) contraindicated.; Other Names: Magnetic Resonance Imaging; Diagnostic test: EKG; At screening and baseline (if not done at screening).; Other Names: Electrocardiogram

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	OS is defined as the median amount of time a participant survives after therapy.	53.7 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Intraperitoneal Progression Free Survival (IPFS) at 6 Months, 12 Months and 18 Months	Intraperitoneal progression free survival is defined as the median amount of time a participant survives from date of operation (hyperthermic intraperitoneal chemotherapy (HIPEC) and gastrectomy) without intraperitoneal disease progression after treatment. Intraperitoneal progression is defined as new, large volume ascites with or without associated peritoneal nodularity or thickening determined by radiographic imaging, cytopathology or histopathology.	6 months, 12 months and 18 months
Extra-peritoneal Disease-free Survival	Extra-peritoneal disease-free survival is defined as the median amount of time a participant survives from date of surgery to the date of first observation of progressive disease at sites other than the peritoneal surface (e.g., liver, intra-abdominal lymph nodes, abdominal wall soft tissues, and any other solid organs) determined by radiographic imaging (i.e., computed tomography, magnetic resonance imaging, and/or positron emission tomography).	48.9 months
Number of Treatment Related Serious and/or Non-serious Adverse Events by Type	The number of treatment related serious and/or non-serious adverse events by type related to research treatments was assessed by the Common Terminology Criteria for Adverse Events (CTCAE v5.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Up to 1646 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Serious and/or Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0)	Here is the number of participants with serious and/or non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life-threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.	Document adverse events from the first study intervention (pre-operation visit) through 30 days after removal from study treatment or until off-study, whichever comes first, approximately 365 days

Collaborators and Investigators

• Sponsor: National Cancer Institute (NCI)
• Investigators: Principal Investigator: Jeremy L Davis, M.D., National Cancer Institute (NCI)

Publications and helpful links

General Publications

• Hartgrink HH, Putter H, Klein Kranenbarg E, Bonenkamp JJ, van de Velde CJ; Dutch Gastric Cancer Group. Value of palliative resection in gastric cancer. Br J Surg. 2002 Nov;89(11):1438-43. doi: 10.1046/j.1365-2168.2002.02220.x.
• Mezhir JJ, Shah MA, Jacks LM, Brennan MF, Coit DG, Strong VE. Positive peritoneal cytology in patients with gastric cancer: natural history and outcome of 291 patients. Ann Surg Oncol. 2010 Dec;17(12):3173-80. doi: 10.1245/s10434-010-1183-0. Epub 2010 Jun 29.
• Kang YK, Yook JH, Chang HM, Ryu MH, Yoo C, Zang DY, Lee JL, Kim TW, Yang DH, Jang SJ, Park YS, Lee YJ, Jung HY, Kim JH, Kim BS. Enhanced efficacy of postoperative adjuvant chemotherapy in advanced gastric cancer: results from a phase 3 randomized trial (AMC0101). Cancer Chemother Pharmacol. 2014 Jan;73(1):139-49. doi: 10.1007/s00280-013-2332-5. Epub 2013 Oct 27.

Helpful Links

• NIH Clinical Center Detailed Web Page

Study record dates

Study Major Dates

• Study Start (Actual): June 5, 2017
• Primary Completion (Actual): April 5, 2024
• Study Completion (Actual): July 24, 2024

Study Registration Dates

• First Submitted: March 22, 2017
• First Submitted That Met QC Criteria: March 22, 2017
• First Posted (Actual): March 28, 2017

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: January 28, 2025
• Last Verified: January 1, 2025

More Information

Terms related to this study

• Keywords: Progression Free Survival; Surgical Resection; Gastroesophageal junction (Siewert III) adenocarcinoma
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Neoplasms, Glandular and Epithelial; Carcinoma; Stomach Neoplasms; Adenocarcinoma; Anti-Bacterial Agents; Anti-Infective Agents; Antibiotics, Antineoplastic; Antineoplastic Agents; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Nucleic Acid Synthesis Inhibitors; Alkylating Agents; Antioxidants; Protective Agents; Antidotes; Antitubercular Agents; Chelating Agents; Sequestering Agents; Mitomycins; Mitomycin; Sodium thiosulfate
• Other Study ID Numbers: 170070; 17-C-0070

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: All individual participant data (IPD) recorded in the medical record will be shared with intramural investigators upon request.
• IPD Sharing Time Frame: Clinical data available during the study and indefinitely.
• IPD Sharing Access Criteria: Clinical data will be made available via subscription to the Biomedical Translational Research Information System (BTRIS) and with the permission of the study principal investigator (PI).
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No