Hyperthermic Intraperitoneal Chemoperfusion (HIPEC) in Gastric Cancer (ProPeC)

Phase II Pilot Study to Reduce the Incidence of Peritoneal Carcinoma After Curative Gastrectomy of Gastric Carcinoma or Adenocarcinoma of Gastroesophageal Transition by Hyperthermic Intraperitoneal Chemoperfusion

This study investigates the effect of a combined therapy with gastrectomy and HIPEC in localized advanced gastric cancer.

Study Overview

• Status: Unknown
• Conditions: Gastric Neoplasms
• Intervention / Treatment: Drug: intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC)

Detailed Description

An operation and the constant further development of the surgical techniques can not always prevent the recurrence of a tumor of the stomach or the transition from the esophagus to the stomach. As reason for this recurrence, the investigators assume that the tumor was already present at the time of the surgery and has crossed the boundaries of the stomach or free tumor cells are located in the peritoneal cavity, even if they can't be found with the bare eye or imaging methods. Such free tumor cells have the possibility of developing metastases within the abdominal cavity.

An innovative local treatment method is being tested in Tübingen and applied to remove any remaining free tumor cells or very small and invisible residual tumors. These free tumor cells can be determined prior to the start of treatment by peritoneal endoscopy (diagnostic laparoscopy). If these can be identified by lavage of the abdominal cavity there is an increased risk for the development of peritoneal metastases. Therefore, in patients with detected free tumor cells in the lavage water of the abdominal cavity, after the removal of the stomach, should be used once a chemotherapy in the abdominal cavity, which is warmer than the body (intraoperative hyperthermic chemotherapy, HIPEC). In this study the investigators want to demonstrate, that the single administration of intraoperative HIPEC with cisplatin and doxorubicin in addition to routine surgery delays the onset of peritoneal metastases and the additional therapy with its low risks is reasonable.

• Study Type: Interventional
• Enrollment (Anticipated): 46
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Alfred Königsrainer, MD; Phone Number: 86620 +49-7071-29-; Email: alfred.koenigsrainer@med.uni-tuebingen.de

Study Locations

• Germany
  • BW
    • Tuebingen, BW, Germany, 72076
      • Recruiting
      • University Department of General, Visceral and Transplant Surgery
      • Contact: Alfred Königsrainer, MD; Phone Number: -86620 +49-7071-29; Email: alfred.koenigsrainer@med.uni-tuebingen.de
      • Principal Investigator: Alfred Königsrainer, MD
      • Sub-Investigator: Can Yurttas, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Written informed consent of the patient
• Positive lavage cytology in staging laparoscopy
• Intraoperative R0- or R1-gastrectomy (Re-evaluation intraoperative)
• Histologically confirmed locally advanced, resectable Adenocarcinomas of the stomach (incl. AEG II-III): >cT3 and/or cN+ and cM0 (none existing solid Peritoneal metastases, Re-evaluation intraoperative)
• Neoadjuvant chemotherapy ≥ 2 cycles

Exclusion Criteria:

• < 18 years
• Existence of contraindications or contraindications against the study medication
• Uncompensated Heart Failure (NYHA III and IV)
• Severe CHD, medically insufficient treatable cardiac arrhythmias, uncontrolled arterial hypertension
• Serum creatinine ≥ 1.5 x the standard value or a Creatinine clearance < 60 ml/min/1.73 m2
• Severe pulmonary dysfunction (COPD, PAH), Pulmonary function test confirmed (IVC < 55 %, DLCO < 40%)
• malignant secondary tumor disease that persists for < 5 years (Exception: in situ carcinoma of the cervix, adequately treated basal cell carcinoma of the skin)
• Participation in other interventional studies that at the time of the ProPeC study inclusion, still are not finished
• pregnancy or lactation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HIPEC-Treatment; Doxorubicin (15 mg/m²/body surface) Cisplatin (75 mg/m²/body surface) applied as hyperthermic intraperitoneal chemotherapy (HIPEC) at 42.5°C for 60 minutes after the gastrectomy. All drugs used are approved.	Drug: intraoperative hyperthermic intraperitoneal chemotherapy (HIPEC); single dose application of hyperthermic intraperitoneal chemotherapy (HIPEC) at 42.5°C for 60 minutes after the gastrectomy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of peritoneal metastases and proportion of patients free from peritoneal metastasis after one year after HIPEC.	The primary objective of the study is to estimate the effect of a combined therapy with gastrectomy and HIPEC in localized advanced gastric cancer. The primary target is the incidence of peritoneal metastases in CT and the proportion of patients who after one year are free from peritoneal metastasis. The study is intended to provide planning data for a subsequent Phase III study in the form of an RCT.	one year

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Overall Survival (OS)	Overall Survival (OS) measured in years.	one year
Progression-free survival (PFS)	Progression-free survival (PFS) based on imaging (CT).	one year
Number of participants with treatment-related adverse events as assessed by grading according to CTCAE v5.0 and Clavien-Dindo.	Expected adverse events (AEs) of particular interest must be recorded from grade ≥ III according to CTCAE v5.0 or postoperative complications according to Clavien-Dindo classification from grade ≥ 3b by AE/ADR reporting. Unexpected and expected AEs must be documented and reported as SAE from grade IV according to CTCAE v5.0 or from grade 4-5 according to Clavien-Dindo classification.	one year

Collaborators and Investigators

• Sponsor: University Hospital Tuebingen

Study record dates

Study Major Dates

• Study Start (ANTICIPATED): November 1, 2019
• Primary Completion (ANTICIPATED): March 1, 2022
• Study Completion (ANTICIPATED): September 1, 2022

Study Registration Dates

• First Submitted: November 7, 2019
• First Submitted That Met QC Criteria: November 26, 2019
• First Posted (ACTUAL): November 29, 2019

Study Record Updates

• Last Update Posted (ACTUAL): November 29, 2019
• Last Update Submitted That Met QC Criteria: November 26, 2019
• Last Verified: November 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: ProPeC

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No