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

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

- 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

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.