Intraperitoneal Paclitaxel and Systemic Therapy Versus Systemic Therapy Alone in Gastric Cancer Patients With Peritoneal Metastasis

Phase 3RecruitingNCT07304271

Magnus Nilsson262 enrolled

Overview

The most common site for gastric cancer distant metastases is the peritoneum. Median survival for this group of patients is short and systemic cytotoxic treatment response is poor, partly due to the low uptake of the treatment compounds to the peritoneum during systemic chemotherapy. Infusion of cytotoxic drugs directly into the abdominal cavity has been shown to have a high objective response rate and low toxicity. The IPa-Gastric trial is an open-label, multicentre, randomised, phase-III study in the first line setting in gastric cancer patients with peritoneal metastases. Patients will receive the study treatments until disease progression, unacceptable side effects, the investigator's decision to end treatment for other reasons, death, or end of study. After discontinuing study treatments, each patient will be followed up for all study endpoints that are clinically feasible, until death or end of study. The primary objective is to compare overall survival (OS) for patients randomised to intraperitoneal (IP) paclitaxel and standard ST versus those randomised to standard ST only.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

262

Conditions

Gastric Cancer Peritoneal Metastases

Interventions

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

Inclusion Criteria: * Gastric or gastro-oesophageal junction Siewert type II or III adenocarcinoma verified by biopsy or cytology from the primary tumour * Peritoneal metastasis verified by biopsy, or cytology from ascites or peritoneal wash fluid * Staging laparoscopy with assessment of peritoneal cancer index (PCI) performed less than four weeks before enrolment. * Patients with tumour positive cytology (CYT+) without clinically manifest peritoneal metastases at baseline (PCI 0) staging laparoscopy can be included if they persist to be CYT+ after at least four cycles of systemic chemotherapy. * Adequate hematology assessment and serum chemistry * Eastern Cooperative Oncology Group (ECOG) performance status 0-1. * Age of at least 18 years * Life expectancy of at least three months * Assurance that adequate anti-reproductive measures will be taken during study interventions when applicable Exclusion Criteria: * Comorbidity that does not allow treatment with ST or IP paclitaxel * Confirmed or suspected severe abdominal adhesions * Severe coagulation disorder which precludes surgical interventions * Distant metastases (including M1 lymph node metastases) other than peritoneal, with the specific exception of ovarian metastases * Symptomatic ascites already requiring drainage for palliation, or expected to require drainage in the short term * Peritoneal recurrence of gastric cancer diagnosed within 6 months after curative intent surgery * Previously received more than 2 cycles of palliative-intent systemic chemotherapy (with the specific exception of cytology positive patients without manifest peritoneal metastases) for the current gastric cancer (up to 2 cycles of first line chemotherapy is allowed). Perioperative chemotherapy within previous curative context is allowed * Another malignancy that can affect survival within the next three years * Known or suspected allergies against any product included in the trial interventions * DYPD deficiency * Pregnancy or recent delivery within 28 days postpartum or ongoing breastfeeding * Active sex-life without use of secure contraceptive method. * If the investigator considers the patient inappropriate for participation in the study for any other reason * Ongoing or recent participation (within 30 days) in a clinical trial with an investigational medicinal product

Outcomes

Primary Outcomes

Overall survival (OS)

Overall survival (OS), defined as time from randomisation to death from any cause. For subjects who are still alive at the End of Study (EoS), or who are lost to follow up, OS time will be censored at the last recorded date that the subject was known to be alive.

Time frame: Assessed every second month from randomization until study completion, during a maximum of 60 months.

Secondary Outcomes

Treatment-related toxicity

Incidence of Adverse Events (AE) as assessed by CTCAE v5.0

Time frame: Assessed continously from start of treatment until 4 weeks after end of treatment for respective participant, during a maximum of 61 months.

General Health Related Quality of Life (HR QoL)

General Health Related Quality of Life (HR QoL) as measured by the European Organisation for Research and Treatment of Cancer (EORTC) quality of life questionnaire QLQ-C30. Two types of scores will be calculated: raw scores and linearly transformed scores.

Time frame: Assessed at baseline and 2, 4, 6, 12 and 24 months after randomisation

Progression free survival (PFS)

PFS is defined as time from randomisation to first documentation of progression according to RECIST1.1, progression of peritoneal carcinomatosis index (PCI), radiological progression of ascites, need for drainage of ascites or death, whichever occurs first.

Time frame: Assessed from randomization until study completion, during a maximum of 60 months.

Radiological response of treatment on ascites present at baseline.

Observed and change from baseline values will be summarized descriptively at planned visits by treatment. A mixed-effects model repeated measures (MMRM) analysis will evaluate longitudinal change from baseline. The baseline score will be included as a covariate.

Time frame: Assessed from baseline visit until study completion, during a maximum of 60 months.

Paracentesis of ascites

Time from randomisation to first paracentesis of ascites

Time frame: Assessed from randomization until study completion, during a maximum of 60 months.

Amount of ascites drained

The sum of the volume drained from each patient from the date of randomisation to date of death, censoring or end of study

Time frame: Assessed from time of randomisation to study completion, during a maximum of 60 months.

Proportion of patients fulfilling the criteria for curative intent conversion surgery.

Criteria for conversion surgery are 1. CYT- at two consecutive sampling occasions, 2. No signs of progression on radiology, 3. No macroscopic peritoneal disease visible at new staging laparoscopy, 4. Discussion at MDT with conversion surgery considered feasible.

Time frame: Assessed from randomisation until study completion, during a maximum of 60 months.

The proportion of patients undergoing conversion surgery

The proportion of patients actually undergoing conversion surgery