Cytoreductive Surgery (CRS) With/Without HIPEC in Gastric Cancer With Peritoneal Carcinomatosis

NCT02158988 | Completed Phase 3 DMC

• 1 other identifier: Gastripec I
• Study Type: interventional
• Target: 105
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (1)

• The primary outcome measure is overall survival

  Overall survival from randomisation up to end of study, follow up every 3 months till 2.5 years

  Death or 2.5 years

Secondary Outcomes (4)

• 30 days complication-rate

  30 days postoperative

• time to progress

  follow up every 3 months till 2.5 years end of study, 2.5 years

• time to other distant metastases

  end of study follow up every 3 months till 2.5 years

• quality of life

  Every 6 months to 2,5 years

Other Outcomes (2)

• frequency of toxicity and adverse events

  every 3 weeks) and thereafter every 3 months up to 2.5 years end of study

• frequency of necessary secondary surgical procedures and the length of hospitalisation

  end of study, every 6 months up to 2.5 years

Study Arms (2)

without HIPEC

NO INTERVENTION

Preoperative chemotherapy 3 cycles, each cycle 21 days. Patients with negative or unknown HER-2 status receive Epirubicin 50 mg/m² infusion (maximum 100mg/d). Oxaliplatin 130 mg/m² infusion (maximum 260 mg/d) and capecitabine oral 625 mg/m² two times a day (maximum 2500 mg/d). Patients with positive HER-2 status receive: Cisplatin : 80 mg/m² infusion (maximum of 160 mg/d). Capecitabine: oral 1000 mg/m2 (two times a day maximum of 4000 mg/d), on day 1-14. Trastuzumab: 8 mg/kg infusion (on cycle 1 and 6 mg/kg on cycle 2 and 3). CRS is performed and 4-12 weeks after CRS 3 cycles of postoperative chemotherapy have to be applied. In case of therapy failure patients will be continued to be treated by the responsible investigator according to his medical status.

With HIPEC

EXPERIMENTAL

Patients will be treated with a preoperative chemotherapy as described for the control group. EOX or CCT depending on the HER-2 status. CRS will be performed 2 to 3 weeks after end of last chemotherapy cycle. HIPEC with mitomycin C and cisplatin either at the time of CRS or a delayed HIPEC within 5-7 days. 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. Patients may get a HIPEC intervention without surgical cytoreduction if contraindication to the drugs can be excluded. In case of therapy failure patients will be continued to be treated by the responsible investigator according to his medical status.

Procedure: HIPEC

Interventions

HIPEC PROCEDURE

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.

With HIPEC

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Charite University, Berlin, Germany: lead
• German Cancer Aid: collaborator

Study Sites (1)

Klinik für Allgemein-, Visceral-, Gefäß- und ThoraxchirurgieCharité Campus Mitte

Berlin, 10117, Germany

Location

Related Publications (1)

• Rau B, Lang H, Koenigsrainer A, Gockel I, Rau HG, Seeliger H, Lerchenmueller C, Reim D, Wahba R, Angele M, Heeg S, Keck T, Weimann A, Topp S, Piso P, Brandl A, Schuele S, Jo P, Pratschke J, Wegel S, Rehders A, Moosmann N, Gaedcke J, Heinemann V, Trips E, Loeffler M, Schlag PM, Thuss-Patience P. Effect of Hyperthermic Intraperitoneal Chemotherapy on Cytoreductive Surgery in Gastric Cancer With Synchronous Peritoneal Metastases: The Phase III GASTRIPEC-I Trial. J Clin Oncol. 2024 Jan 10;42(2):146-156. doi: 10.1200/JCO.22.02867. Epub 2023 Oct 31.

  PMID: 37906724 DERIVED

MeSH Terms

Conditions

Stomach Neoplasms; Peritoneal Neoplasms

Interventions

Hyperthermic Intraperitoneal Chemotherapy

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Abdominal Neoplasms; Peritoneal Diseases

Intervention Hierarchy (Ancestors)

Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced

Study Officials

• Beate Rau, Prof.

  Charite University, Berlin, Germany

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof.

Model Details: intraperitoneal (in the abdominal cavity) chemoperfusion with Mitomycin C and Cisplatin

Study Record Dates

• First Submitted: May 4, 2014
• First Posted: June 9, 2014
• Study Start: March 1, 2014
• Primary Completion: October 1, 2020
• Study Completion: June 9, 2021
• Last Updated: July 29, 2021

Record last verified: 2021-07

Locations

DE (1)