Clinical trial NCT05318794: Neoadjuvant Systemic and Peritoneal Chemotherapy for Advanced Gastric Cancer
Official title: Neoadjuvant Systemic and Peritoneal Chemotherapy for Regionally Advanced Gastric Cancer With Minimal Peritoneal Disease
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Gastric Cancer
Peritoneal Metastases
Chemotherapy Effect
Keywords: Pressurised intraperitoneal aerosol chemotherapy
PIPAC
Neoadjuvant therapy
Gastrectomy
Curative
Doxorubicin
Cisplatin
Lead sponsor: Imperial College London
Sponsor class: OTHER
First posted: 2022-04-08
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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

Primary outcomes:
measure: Feasibility and safety of combined neoadjuvant systemic chemotherapy and pressurised intraperitoneal aerosol chemotherapy (PIPAC)
timeFrame: 2 years
Secondary outcomes:
measure: Tumour regression
timeFrame: 2 years
measure: Patient morbidity
timeFrame: 2 years
measure: Health related quality of life
timeFrame: 2 years
measure: Disease recurrence and survival
timeFrame: 5 years
Other outcomes:
Locations:
city: London
country: United Kingdom
facility: Imperial College London, Hammersmith Hospital Campus
Study officials:
affiliation: Imperial College London
name: George B Hanna, FRCS, PhD
role: PRINCIPAL_INVESTIGATOR
References: