Cytoreductive Surgery and Intraperitoneal Chemotherapy for Stomach CAncer: a Feasibility Study

NCT03150628 | Terminated Phase 2 DMC

• 3 other identifiers: NL58258.041.162016-002595-2716-180/G-M
• Study Type: interventional
• Target: 3
• Locations: 1 country
• Sites: 1

Brief Summary

Rationale: For patients with peritoneal metastases of gastric origin, there is no consensus on the optimal treatment strategy. Several Asian and Western studies demonstrated hyperthermic intraperitoneal chemotherapy (HIPEC) and cytoreductive surgery (CS) to result in a prolonged survival compared to palliative systemic treatment. Morbidity and mortality rates of HIPEC and CS appear to be acceptable. In the Netherlands, this treatment is not yet introduced, therefore patients with peritoneal metastases of gastric origin are precluded from surgery and will be treated with palliative chemotherapy or best support of care. Objective: To assess the safety and feasibility of HIPEC and CS in Western patients with peritoneal metastases of gastric cancer, in terms of morbidity and mortality. Secondary objective is to determine the effect on survival and recurrence. Study design: Mono centre prospective phase II single-arm feasibility study. Study population: Western patients diagnosed with resectable (cT1-4b, N1-3) gastric cancer with clinical or pathologically proven peritoneal metastases without distant metastases. Intervention: Hyperthermic Intraperitoneal Chemotherapy (HIPEC) and Cytoreductive Surgery (CS) with Cisplatin. Main study parameters/endpoints: Primary outcome is the safety and feasibility of the intervention, measured by the percentage of overall surgical complications grade ≥3 as stated by the Common Terminology Criteria for Adverse Events. Secondary outcomes are intraoperative events, postoperative morbidity and mortality, postoperative recovery, including quality of life, and disease free- and overall survival. Nature and extent of the burden and risks associated with participation, benefit and group relatedness: The additional burden for the patient mainly consists of HIPEC and CS.Furthermore, patients will undergo additional staging in order to exclude unresectable disease, and neoadjuvant chemotherapy regimen (3 drugs) instead of a palliative chemotherapy regimen (2 drugs). Postoperative care and outpatient visits are performed according to current protocols on HIPEC and CS for colon cancer and nation-wide protocols on gastric cancer surgery. The study is associated with a high risk classification. As there is a potential survival benefit, a small chance for curation and possibly a higher quality of life, we consider the additional burden and risks justified. This study is designed as a one group study, which eliminates group relatedness.

Conditions

Gastric Cancer; Peritoneal Carcinomatosis; HIPEC

Outcome Measures

Primary Outcomes (2)

• Morbidity

  Common Terminology Criteria for Adverse Events (CTCAE) ≥ grade 3

  From the day of surgery to hospital discharge or 30 days postoperative, whichever is last

• Mortality

  Postoperative mortality

  From the day of surgery to 30 days postoperative

Secondary Outcomes (4)

• Survival

  Up to 5 years postoperative

• Recovery

  From the day of surgery to hospital discharge or 30 days postoperative, whichever is last

• Quality of Life

  Up to 5 years postoperative

• Readmissions

  Up to 30 days after hospital discharge

Study Arms (1)

Study population

EXPERIMENTAL

Drug: Perioperative chemotherapy; Procedure: Cytoreduction; Drug: HIPEC

Interventions

Perioperative chemotherapy DRUG

Perioperative chemotherapy

Study population

Cytoreduction PROCEDURE

Cytoreductive surgery

Study population

HIPEC DRUG

Hyperthermic intraperitoneal chemotherapy (HIPEC) with 100mg/m2 cisplatin

Study population

Eligibility Criteria

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

You may qualify if:

• Histologically proven adenocarcinoma of the stomach.
• Surgical resectable carcinoma (T1-4b, N1-3) (table 1)
• Pathological proven peritoneal metastases
• Peritoneal Cancer Index (PCI) ≤12
• WHO performance status 0,1 or 2 and ASA 1-3
• Age ≥ 18
• Written informed consent

You may not qualify if:

• Distant metastases other than peritoneal metastases
• Siewert type I/II gastro-esophageal junction tumor 22.
• Peritoneal carcinomatosis as a presentation of recurrent disease
• Pregnancy
• Any contraindication to cisplatin, e.g.
• Hypersensitivity
• HIV infection
• inadequate bone marrow function (ANC \<1.5x109/L or Platelets \<100x109/L)
• inadequate hepatic function (\>1.5 x ULN, ALAT and ASAT \>2.5 x ULN)
• inadequate renal function (Creatinine clearance \<50 ml/min)

Sponsors & Collaborators

• Richard van Hillegersberg: lead

Study Sites (1)

University Medical Center Utrecht

Utrecht, 3584 CX, Netherlands

Location

Related Publications (3)

• Coccolini F, Cotte E, Glehen O, Lotti M, Poiasina E, Catena F, Yonemura Y, Ansaloni L. Intraperitoneal chemotherapy in advanced gastric cancer. Meta-analysis of randomized trials. Eur J Surg Oncol. 2014 Jan;40(1):12-26. doi: 10.1016/j.ejso.2013.10.019. Epub 2013 Nov 5.

  PMID: 24290371 BACKGROUND

• Chia CS, You B, Decullier E, Vaudoyer D, Lorimier G, Abboud K, Bereder JM, Arvieux C, Boschetti G, Glehen O; BIG RENAPE Group. Patients with Peritoneal Carcinomatosis from Gastric Cancer Treated with Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy: Is Cure a Possibility? Ann Surg Oncol. 2016 Jun;23(6):1971-9. doi: 10.1245/s10434-015-5081-3. Epub 2016 Jan 11.

  PMID: 26753751 BACKGROUND

• Glehen O, Gilly FN, Arvieux C, Cotte E, Boutitie F, Mansvelt B, Bereder JM, Lorimier G, Quenet F, Elias D; Association Francaise de Chirurgie. Peritoneal carcinomatosis from gastric cancer: a multi-institutional study of 159 patients treated by cytoreductive surgery combined with perioperative intraperitoneal chemotherapy. Ann Surg Oncol. 2010 Sep;17(9):2370-7. doi: 10.1245/s10434-010-1039-7. Epub 2010 Mar 25.

  PMID: 20336386 BACKGROUND

MeSH Terms

Conditions

Stomach Neoplasms; Peritoneal Neoplasms

Interventions

Cytoreduction Surgical Procedures; 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)

Surgical Procedures, Operative; Chemotherapy, Adjuvant; Combined Modality Therapy; Therapeutics; Drug Therapy; Hyperthermia, Induced

Study Officials

• Richard van Hillegersberg, MD PhD

  UMC Utrecht Cancer Center, Dep. of Surgery

  PRINCIPAL INVESTIGATOR

• Jelle P Ruurda, MD PhD

  UMC Utrecht Cancer Center, Dep. of Surgery

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: April 4, 2017
• First Posted: May 12, 2017
• Study Start: August 1, 2017
• Primary Completion: April 23, 2018
• Study Completion: April 23, 2018
• Last Updated: April 17, 2019

Record last verified: 2019-04

Data Sharing

• IPD Sharing: Will not share

Locations

NL (1)