Malignant Neoplasm of Stomach, Secondary Malignant Neoplasm of Other and Unspecified Sites, Secondary Malignant Neoplasm of Peritoneum
Conditions
Keywords
Gastric cancer, cancer of the esophagogastric junction, peritoneal carcinomatosis, hyperthermic intraperitoneal chemotherapy, HIPEC
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.
Interventions
PROCEDUREHIPEC
HIPEC: Mitomycin C: 15 mg/m2 (max. 30 mg/ m2, max. 5 L Perfusion). Cisplatin: 75 mg/m2/L (max. 150 mg/m2, max. 5 L Perfusion). 4-12 weeks after cytoreductive surgery 3 cycles postoperative chemotherapy will be applied.
Sponsors
German Cancer Aid
Charite University, Berlin, Germany
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Intervention model description
intraperitoneal (in the abdominal cavity) chemoperfusion with Mitomycin C and Cisplatin
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The primary outcome measure is overall survival | Death or 2.5 years | Overall survival from randomisation up to end of study, follow up every 3 months till 2.5 years |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| 30 days complication-rate | 30 days postoperative | 30 days complication-rate. Complications are ranked from grade 0-5 according to CTCAE V4.0 |
| time to progress | follow up every 3 months till 2.5 years end of study, 2.5 years | time to progress of tumor, follow up every 3 months till 2.5 years |
| time to other distant metastases | end of study follow up every 3 months till 2.5 years | time to other distant metastases follow up every 3 months till 2.5 years |
| quality of life | Every 6 months to 2,5 years | quality of life (EORTC QLQ-30, STO 22). Every 6 months to 2,5 years |
Other
| Measure | Time frame | Description |
|---|---|---|
| frequency of toxicity and adverse events | every 3 weeks) and thereafter every 3 months up to 2.5 years end of study | frequency of toxicity and adverse events, visit 1-11 (every 3 weeks) and thereafter every 3 months up to 2.5 years. AE is documented with the date of the begin and the end of the AE and the intensity according to CTCAE V4.0 |
| frequency of necessary secondary surgical procedures and the length of hospitalisation | end of study, every 6 months up to 2.5 years | frequency of necessary secondary surgical procedures and the length of hospitalisation every 6 months up to 2.5 years . The date of the begin and the end is daocumented as well as the reasons |
Countries
Germany
Outcome results
None listed