Cytoreductive Surgery and Hyperthermic Intraperitoneal Mitomycin C Followed by Standard Chemotherapy in Treating Patients with Peritoneal Carcinomatosis

Status: Active

Description

This phase II trial studies how well cytoreductive surgery and hyperthermic intraperitoneal mitomycin C followed by standard chemotherapy works in treating patients with peritoneal carcinomatosis. Cytoreductive surgery helps to reduce the number of cancer cells prior to treatment. Hyperthermia therapy kills tumor cells by heating them to several degrees above normal body temperature. Drugs used in chemotherapy, such as mitomycin C, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Infusing mitomycin C directly into the abdomen may kill more tumor cells while reducing side effects. Giving cytoreductive surgery with hyperthermic intraperitoneal mitomycin C may kill more tumor cells.

Eligibility Criteria

Inclusion Criteria

  • Capable of providing informed consent
  • The patient who has not previously received hyperthermic intraperitoneal chemotherapy must have histopathologically or cytologically confirmed cancer from peritoneal mesothelioma, pseudomyxoma, or gastrointestinal malignancies (excluding pancreatic and hepatobiliary) with known synchronous or metachronous disease dissemination limited to the peritoneal surfaces
  • The patient must have documented disease limited to the peritoneal surface, amenable to complete cytoreduction indicated by: * Disease confined to the peritoneal surfaces * No parenchymal liver metastases * No evidence of clinical, biochemical or radiological biliary obstruction * Small volume of disease in the gastro-hepatic ligament defined by a < 5 cm mass in the epigastric region on cross-sectional imaging * No clinical or radiological evidence of hematogenous or distant nodal metastasis
  • Eastern Cooperative Oncology Group (ECOG) performance status of =< 1
  • Absolute neutrophil count (ANC) > 1500/mm^3
  • White blood cell count (WBC) > 4000/mm^3
  • Platelet count > 100,000/mm^3
  • An international normalized ratio (INR) =< 1.5 (patients who are therapeutically anticoagulated for unrelated medical conditions such as atrial fibrillation and whose antithrombotic treatment can be withheld for operation will be eligible)
  • Total serum bilirubin =< 1.5 mg/dl (patients with total bilirubin > 1.5 mg/dL eligible only with Gilbert’s syndrome)
  • Alkaline phosphatase < 2.5 times the upper limit of normal
  • Aspartate aminotransferase (AST) < 1.5 times upper limit of normal (alkaline phosphatase and AST cannot both exceed the upper limit of normal)
  • Creatinine < 1.5 x the upper limit of normal (ULN) or calculated creatinine clearance of >= 50ml/min
  • Satisfactory cardiopulmonary function (no history of severe congestive heart failure or severe pulmonary disease, as indicated by clinically acceptable risks to undergo major abdominal - cytoreductive surgery)
  • Patients who have met the above criteria and who have undergone CRS and HIPEC in the past 18 months for the forementioned disease processes without evidence of recurrence will be eligible for participation in this study for analyzing ability to achieve complete cytoreduction, morbidity, progression and survival

Exclusion Criteria

  • The patients have documented disease beyond the peritoneal surfaces, which prevent achieving complete cytoreduction as indicated by: * Evidence of distant hematogenous metastatic disease or distant nodal metastases * Evidence of parenchymal hepatic metastases * Evidence of clinical, biochemical or radiological biliary obstruction * Evidence of gross disease of the small bowel mesentery characterized by distortion, thickening or loss of mesenteric vascular clarity which limits ability to obtain complete cytoreduction
  • Significant history of a medical problem or co-morbidity that would preclude the patient from undergoing a major abdominal operation such as a history of severe congestive heart failure or active ischemic heart disease
  • Active systemic infections, coagulation disorders, or other major medical illnesses precluding major surgery
  • Childs B or C cirrhosis or with evidence of severe portal hypertension by history, endoscopy or radiologic studies
  • Significant chronic obstructive pulmonary disease (COPD) or other chronic pulmonary restrictive disease with pulmonary function tests (PFTs) indicating a forced expiratory volume in one second (FEV1) less than 50% or a diffusion capacity of carbon monoxide (DLCO) less than 40% predicted for age
  • Psychiatric or addictive disorders or other conditions that would preclude the patient from meeting the study requirements
  • Patients in pregnant or lactating
  • Patients with a body mass index (BMI) of 40 or more

Locations & Contacts

New York

Bronx
Montefiore Medical Center-Weiler Hospital
Status: Active
Contact: Haejin In
Email: hin@montefiore.org

Trial Objectives and Outline

PRIMARY OBJECTIVES:

I. This prospective trial will evaluate the technical parameters including completeness of cytoreduction, achievement of hyperthermia, morbidity and mortality in patients with peritoneal carcinomatosis of colorectal, gastric, appendiceal, pseudomyxoma peritonei and peritoneal mesothelioma origin undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy with mitomycin C.

SECONDARY OBJECTIVES:

I. To evaluate time to progression and progression free survival (PFS) for patients with peritoneal carcinomatosis treated with cytoreductive surgery (CRS) + hyperthermic intraperitoneal chemotherapy (HIPEC).

II. To evaluate overall survival for patients with peritoneal carcinomatosis treated with CRS + HIPEC.

III. To assess quality of life (QOL) score for patients undergoing CRS + HIPEC.

IV. To evaluate epigenetic and genomic changes following treatment with HIPEC and association of these changes with improved progression free survival.

OUTLINE:

Patients undergo cytoreduction surgery and hyperthermic mitomycin C intraperitoneally (IP) over 90 minutes. After surgery and hyperthermia treatment, patients receive standard systemic chemotherapy.

After completion of study treatment, patients are followed up every 3 months for 1 year and then every 6 months for 4 years.

Trial Phase & Type

Trial Phase

Phase II

Trial Type

Treatment

Lead Organization

Lead Organization
Montefiore Medical Center-Weiler Hospital

Principal Investigator
Haejin In

Trial IDs

Primary ID 11-09-332
Secondary IDs NCI-2013-01214, 11-075
Clinicaltrials.gov ID NCT02040142