Neoadjuvant Systemic and Peritoneal Chemotherapy for Advanced Gastric Cancer

NCT ID: NCT05318794

Last Updated: 2023-09-13

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-11-30
• Study Completion Date: 2030-07-31

Brief Summary

Data demonstrating the efficacy of PIPAC in patients with regionally advanced gastric cancer with positive peritoneal cytology and/or minimal peritoneal disease is limited due to the relatively recent development of this technique and its historical preferential use in palliative patients with disseminated peritoneal metastasis.

Existing data suggest PIPAC administered every six weeks in conjunction with standard treatment may work as an adjunct to conventional systemic neoadjuvant chemotherapy. PIPAC protocols have been established both for gastric cancer as well as other intra-abdominal malignancies and have a good safety profile.

Given these promising findings, a study protocol is proposed herein to further investigate PIPAC for the treatment of a highly selected group of patients with regionally advanced gastric cancer (positive peritoneal cytology and/or minimal peritoneal disease).

Detailed Description

BACKGROUND:

There remains therefore an important, and as yet unmet, clinic need to improve survival of patients with regionally advanced gastric cancer with positive peritoneal cytology and/or minimal peritoneal disease.

To address this challenge, there has been emerging interest in the use of intraperitoneal chemotherapy for the treatment and suppression of peritoneal disease in patients with regionally advance gastric cancer.

HYPOTHESIS:

Use of combined neoadjuvant systemic chemotherapy and PIPAC in a highly selected group of patients with locally advanced gastric cancer (positive cytology and/or minimal peritoneal disease) is safe and will effectively eradicate all traces of peritoneal metastasis.

STUDY DESIGN:

This will be a non-randomised interventional cohort study of patients with regionally advanced gastric cancer (Tx, Nx) with either positive peritoneal cytology and/or minimal peritoneal disease (peritoneal carcinomatosis index, PCI ≤ 3). All patients will undergo complete cancer staging, including laparoscopy.

Prior to enrolment Potentially eligible patient will be reviewed by the Northwest London Upper Gastrointestinal Cancer Multidisciplinary Team. Study recruitment will also be open to eligible patients referred from other regional cancer networks within England. Study recruitment will also be open to eligible patients referred from other regional cancer networks within England.

Eligible patients will receive systemic chemotherapy (in accordance with local protocols) and PIPAC (Doxorubicin 1.5 mg/m2 body surface area Cisplatin 7.5 mg/m2 body surface area). Patients will receive three cycles of systemic chemotherapy interposed with three PIPAC sessions. Chemotherapy cycles will be occur at six weekly intervals.

Following completion of neoadjuvant systemic chemotherapy and PIPAC patients will be restaged. Patients will be considered eligible for D2 radical gastrectomy if the following conditions are met:

(i) negative peritoneal cytology; (ii) absence of macroscopic peritoneal metastasis (PCI 0); (iii) absence of solid organ metastasis (for T4b disease please see point iv below); (iv) expectation of complete (R0) resection of primary tumour; (v) patient considered medically fit for gastrectomy (performance status ≤ 1, absence of organ failure or uncontrolled co-morbidity), and; (vi) provision of informed written consent for treatment (surgery)

Patients who do not meet these criteria will be offered continued palliative and/or best supportive care.

Conditions

Gastric Cancer; Peritoneal Metastases; Chemotherapy Effect

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Neoadjuvant systemic and peritoneal chemotherapy

Standard neoadjuvant systemic and pressurised intraperitoneal aerosol chemotherapy

Group Type: EXPERIMENTAL

Doxorubicin and Cisplatin

Intervention Type: DRUG

Pressurised intraperitoneal aerosol chemotherapy

Interventions

Doxorubicin and Cisplatin

Pressurised intraperitoneal aerosol chemotherapy

Intervention Type: DRUG

Other Intervention Names

Adriamycin

Eligibility Criteria

Inclusion Criteria

• Gastric adenocarcinoma (Tx, Nx) 1,2,3
• Peritoneal cytology +ve or PCI ≤ 3
• No solid organ metastasis 2
• HER2 -ve
• Male/female
• Treatment naïve
• BMI ≥ 18.5 kg/m2 or ≤ 40 kg/m2
• WHO performance status ≤ 1
• Dysphagia score ≤ 2
• Informed written consent

Exclusion Criteria

• PCI ≥ 4
• Solid organ metastasis
• Positive lymph node disease beyond field of D2 lymphadenectomy
• Peritoneal adhesions precluding complete laparoscopy
• Ascites (greater than trace amount)
• Malignant pleural effusion
• Mechanical bowel obstruction (with the exception of gastric outlet obstruction)
• HER2 +ve
• Patients eligible for immunotherapy
• Uncontrolled co-morbidity
• single/multiple organ failure
• BMI < 18.5 kg/m2 or > 40 kg/m2
• WHO performance status > 1
• Dysphagia score > 2
• Contraindication to chemotherapy
• Pregnancy or breastfeeding
• Haemoglobin <90 g/dL uncorrected with blood transfusion

• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Imperial College London

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

George B Hanna, FRCS, PhD

Role: PRINCIPAL_INVESTIGATOR

Imperial College London

Locations

Imperial College London, Hammersmith Hospital Campus

London, , United Kingdom

Countries

United Kingdom

Central Contacts

Piers R Boshier, FRCS, PhD

Role: CONTACT

prb03@ic.ac.uk

020 7594 8197

Facility Contacts

George B Hanna, FRCS, PhD

Role: primary

g.hanna@imperial.ac.uk

020 7594 8197

Piers R Boshier, FRCS, PhD

Role: backup

prb03@ic.ac.uk

020 7594 8197

Other Identifiers

313621

Identifier Type: -

Identifier Source: org_study_id