Clinical trial NCT02158988: Cytoreductive Surgery (CRS) With/Without HIPEC in Gastric Cancer With Peritoneal Carcinomatosis
Official title: Prospective Multicenter Phase III Trial Using CRS With / Without HIPEC After Preoperative Chemotherapy in Patients With Peritoneal Carcinomatosis of Gastric Cancer Incl. Adenocarcinoma of the Esophagogastric Junction
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Malignant Neoplasm of Stomach
Secondary Malignant Neoplasm of Peritoneum
Secondary Malignant Neoplasm of Other and Unspecified Sites
Keywords: Gastric cancer
cancer of the esophagogastric junction
peritoneal carcinomatosis
hyperthermic intraperitoneal chemotherapy
HIPEC
Lead sponsor: Charite University, Berlin, Germany
Sponsor class: OTHER
Collaborators: name: German Cancer Aid
First posted: 2014-06-09
Enrollment: 105
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: intraperitoneal (in the abdominal cavity) chemoperfusion with Mitomycin C and Cisplatin
Primary purpose: TREATMENT

Brief summary: Patients with histological proven gastric cancer (including cancer of the esophagogastric junction (AEG)) and synchronous peritoneal carcinomatosis, who fulfill the inclusion and exclusion criteria, can be recruited in this study. There are two treatment groups (A and B). The chemotherapy applied intravenously is the same in both groups and is approved for the treatment of gastric cancer. Patients with negative or unknown HER-2 status will be administered Epirubicin, Oxaliplatin and Capecitabine (EOX). Patients with positive HER-2 status will be treated with Cisplatin, Capecitabine and Trastuzumab (CCT).

The chemotherapy is followed by surgical cytoreduction in both groups. Patients randomized into group B will be treated with an intraperitoneal (in the abdominal cavity) chemoperfusion with Mitomycin C and Cisplatin .

Patients in both groups receive 3 cycles of postoperative chemotherapy within 4-12 weeks after the surgical procedure and are followed up for 30 months.

If progress of the tumor is detected the patient will no longer be treated according to the study therapy. Patients of group B may get a HIPEC intervention without surgical cytoreduction if contraindication to the drugs applied can be excluded.

Detailed description: The objective of the trial is to compare the treatment of patients with peritoneal metastasized gastric cancer including carcinoma of the AEG (Adenocarcinoma of the oesophago-gastric-junction) without evidence of other distant metastases treated with neoadjuvant chemotherapy followed by cytoreduction with intraperitoneal chemoperfusion (HIPEC) and postoperative chemotherapy (Group B) and patients treated with cytoreduction alone after neoadjuvant chemotherapy and postoperative chemotherapy (Group A).

Hypothesis of the trial is that surgical cytoreduction with intraperitoneal chemoperfusion (Group B) is superior to cytoreduction alone (Group A) in terms of overall survival.

The trial is designed as a prospective, randomized, open, multicenter and parallel group study.

Eligibility criteria: Inclusion Criteria:

* Histological proved diagnosis of peritoneal metastasized gastric cancer including carcinoma of the AEG No evidence of other distant metastases than peritoneal carcinomatosis with exception of Krukenberg Tumors
* Peritoneal Staging with laparoscopy (or explorative laparotomy) and estimation of Peritoneal Cancer Index (PCI) with the possibility of 80% tumor reduction at cytoreductive surgery
* Karnofsky Index 70% or better
* Written informed consent is obtained prior to commencement of trial treatment

Exclusion Criteria:

* Other than peritoneal metastasis of the gastric cancer incl. AEG and Krukenberg tumors
* Previous or concurrent malignancies, with the exception of adequately treated basal cell carcinoma of the skin or in situ carcinoma of the cervix
* Any previous chemotherapy or radiotherapy, and any investigational treatment for gastric cancer
* Active systemic infections
* Patients with known interstitial lung disease with New York Heart Association classification \> 2
* Serious cardiac dysrhythmia or condition, New York Heart Association classification of III or IV, congestive cardiac failure
* cardiac arrhythmia
* Uncontrolled hypertension (diastolic blood pressure constantly \>100 mm Hg, systolic blood pressure constantly \> 180 mm Hg).
* Inadequate bone marrow function at the beginning of the trial, defined as platelet count less than \<150 GPT/L or neutrophil granulocyte count less than \<1.5 GPT/L
* cardiac function EF \< 55%
* Inadequate renal function at the beginning of the trial, defined as GFR less than \<60 ml/min
* Inadequate liver function at the beginning of the trial, defined as Bilirubin \>1.5 times ULN
* Active vaccination within 6 weeks prior to randomisation
* Active hepatitis B or C infection
* Female patients who are pregnant or breast feeding
* Fertile female patients (defined as women with less than a 12-month elapse after the last menstruation) not using an acceptable form of contraception during the trial
* Missing of capacity to contract
* contraindication to the drugs which are used in the trial
* Participation in another therapeutic clinical trial
* Persons institutionalised due to regulatory actions ore by court order.

Primary outcomes:
measure: The primary outcome measure is overall survival
timeFrame: Death or 2.5 years
Secondary outcomes:
measure: 30 days complication-rate
timeFrame: 30 days postoperative
measure: time to progress
timeFrame: follow up every 3 months till 2.5 years end of study, 2.5 years
measure: time to other distant metastases
timeFrame: end of study follow up every 3 months till 2.5 years
measure: quality of life
timeFrame: Every 6 months to 2,5 years
Other outcomes:
measure: frequency of toxicity and adverse events
timeFrame: every 3 weeks) and thereafter every 3 months up to 2.5 years end of study
measure: frequency of necessary secondary surgical procedures and the length of hospitalisation
timeFrame: end of study, every 6 months up to 2.5 years
Locations:
city: Berlin
country: Germany
facility: Klinik für Allgemein-, Visceral-, Gefäß- und ThoraxchirurgieCharité Campus Mitte
Study officials:
affiliation: Charite University, Berlin, Germany
name: Beate Rau, Prof.
role: STUDY_DIRECTOR
References: