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

Sponsor

National Cancer Institute (NCI) (NIH)

Overall Status

Recruiting

CT.gov ID

NCT03092518

Collaborator

(none)

Enrollment

Location

Arm

123.9

Anticipated Duration (Months)

0.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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 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 might 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 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.

Condition or Disease	Intervention/Treatment	Phase
Gastric Adenocarcinoma Esophagogastric Junction Gastric Cancer	Procedure: Surgery Drug: Cisplatin Drug: Mitomycin C Drug: Sodium Thiosulfate	Phase 2

Detailed Description

Background:

An estimated 24,590 cases of gastric adenocarcinoma are diagnosed annually in the 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 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 Design

Study Type:

Interventional

Anticipated Enrollment :

40 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Jun 5, 2017

Anticipated Primary Completion Date :

Oct 1, 2025

Anticipated Study Completion Date :

Oct 1, 2027

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1/Arm 1 HIPEC with gastrectomy	Procedure: Surgery Heated Intraperitonial Chemotherapy (HIPEC) with gastrectomy using cisplatin, mitomycin C and sodium thiosulfate Drug: Cisplatin Cisplatin (90 mg/m2) will be administered via circuit to the peritoneal cavity Drug: Mitomycin C Mitomycin C 10 mg/m2 will be administered via circuit to the peritoneal cavity 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.

Arm

Intervention/Treatment

Experimental: 1/Arm 1

HIPEC with gastrectomy

Procedure: Surgery

Heated Intraperitonial Chemotherapy (HIPEC) with gastrectomy using cisplatin, mitomycin C and sodium thiosulfate

Drug: Cisplatin

Cisplatin (90 mg/m2) will be administered via circuit to the peritoneal cavity

Drug: Mitomycin C

Mitomycin C 10 mg/m2 will be administered via circuit to the peritoneal cavity

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.

Outcome Measures

Primary Outcome Measures

Overall survival [death]
median amount of time subject survives after therapy

Secondary Outcome Measures

intraperitoneal progression free survival [at intraperitoneal progression]
median amount of time subject survives without intraperitoneal disease progression after treatment
extra-peritoneal disease free survival [at extraperitoneal progression]
median amount of time subject survives without extraperitoneal disease progression after treatment
morbidity [5 years]
list of adverse event frequency

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

INCLUSION CRITERIA:
Patients must have histologically or cytologically confirmed gastric adenocarcinoma or gastroesophageal junction (Siewert I-III) adenocarcinoma confirmed by the Laboratory of Pathology, 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 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.
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

AST(SGOT)/ALT(SGPT) less than or equal to 2.5 X institutional upper limit of normal

creatinine < 1.5 mg/dl

eGFR (creatinine clearance) greater than or equal to 60 mL/min/1.73 m2.

Physiologically able to undergo 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 infants secondary to treatment of the mother with HIPEC and gastrectomy, breastfeeding should be discontinued if the mother is treated on this study.
HIV-positive patients may be considered for this study only after consultation with a NIAID physician.