Intraperitoneal Paclitaxel and Systemic Therapy Versus Systemic Therapy Alone in Gastric Cancer Patients With Peritoneal Metastasis (IPa-Gastric)

Randomised Phase III Trial of First Line Intraperitoneal Paclitaxel and Systemic Therapy Versus Systemic Therapy Alone in Gastric Cancer Patients With Peritoneal Metastases - IPa-Gastric

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 Overview

• Status: Recruiting
• Conditions: Gastric Cancer Peritoneal Metastases
• Intervention / Treatment: Drug: Standard systemic therapy; Drug: Intraperitoneal Paclitaxel

• Study Type: Interventional
• Enrollment (Estimated): 262
• Phase: Phase 3

Contacts and Locations

• Study Contact: Name: Magnus Nilsson, MD, Professor; Phone Number: +46 8 123 800 00; Email: magnus.nilsson@ki.se
• Study Contact Backup: Name: Lisa Liu Burström, MD, PhD; Phone Number: +46 8 123 700 00; Email: lisa.liu@ki.se

Study Locations

• Italy
  • Verona, Italy, 37126
    • Not yet recruiting
    • Azienda Ospedaliera Universitaria Integrata Verona
    • Contact: Maria Bencivenga, MD, PhD; Phone Number: +390458121111; Email: maria.bencivenga@univr.it
    • Contact: Bencivenga; Email: maria.bencivenga@univr.it
    • Principal Investigator: Maria Bencivenga, MD, PhD
• Sweden
  • Gothenburg, Sweden, 413 46
    • Not yet recruiting
    • Sahlgrenska University Hospital
    • Contact: Mia Johansson, MD, PhD; Phone Number: +46313421000; Email: mia.i.johansson@vgregion.se
    • Principal Investigator: Mia Johansson, MD, PhD
  • Stockholm, Sweden, 171 76
    • Recruiting
    • Karolinska University Hospital
    • Contact: Lisa Liu Burström, MD, PhD; Phone Number: +46 8 123 700 00; Email: lisa.liu-burstrom@regionstockholm.se
    • Principal Investigator: Lisa Liu Burström, MD, PhD
  • Uppsala, Sweden, SE-751 85
    • Not yet recruiting
    • Uppsala University Hospital
    • Principal Investigator: Jakob Hedberg, MD, PhD
    • Contact: Jakob Hedberg, MD, PhD; Phone Number: +46186110000; Email: jakob.hedberg@uu.se
    • Contact: Hedberg; Email: jakob.hedberg@uu.se
  • Örebro, Sweden, SE-701 85
    • Not yet recruiting
    • Orebro University Hospital
    • Contact: Ida Lagstam, MD, PhD; Phone Number: +49196021000; Email: ida.lagstam@regionorebrolan.se
    • Principal Investigator: Ida Lagstam, MD, PhD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Standard systemic therapy; The control arm treatment in the study will consist of standard investigator's choice therapy with systemic chemotherapy and any targeted therapies indicated in the standard clinical practice setting	Drug: Standard systemic therapy; Standard investigator's choice therapy with systemic chemotherapy and any targeted therapies indicated in the standard clinical practice setting
Experimental: Intraperitoneal paclitaxel + Standard systemic therapy; The experimental arm treatment will consist of the same standard systemic investigator's choice treatment described above combined with IP paclitaxel.	Drug: Standard systemic therapy; Standard investigator's choice therapy with systemic chemotherapy and any targeted therapies indicated in the standard clinical practice setting; Drug: Intraperitoneal Paclitaxel; Intraperitoneally administered Paclitaxel

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	Assessed every second month from randomization until study completion, during a maximum of 60 months.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Treatment-related toxicity	Incidence of Adverse Events (AE) as assessed by CTCAE v5.0	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.	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.	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.	Assessed from baseline visit until study completion, during a maximum of 60 months.
Paracentesis of ascites	Time from randomisation to first paracentesis of ascites	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	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.	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	Assessed from randomisation until study completion, during a maximum of 60 months.

Collaborators and Investigators

• Sponsor: Magnus Nilsson
• Investigators: Study Director: Magnus Nilsson, MD, Professor, Karolinska University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 5, 2025
• Primary Completion (Estimated): January 31, 2031
• Study Completion (Estimated): January 31, 2031

Study Registration Dates

• First Submitted: November 19, 2025
• First Submitted That Met QC Criteria: December 12, 2025
• First Posted (Actual): December 26, 2025

Study Record Updates

• Last Update Posted (Actual): December 26, 2025
• Last Update Submitted That Met QC Criteria: December 12, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Gastric cancer; Peritoneal metastasis; Intraperitoneal administration
• Additional Relevant MeSH Terms: Neoplasms by Site; Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Stomach Diseases; Stomach Neoplasms
• Other Study ID Numbers: 2024-514879-17-00

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: A plan for IPD sharing will be added later

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