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

Official title

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

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.

Interventions

• Drug Intraperitoneal Paclitaxel
  Intraperitoneally administered Paclitaxel
• Drug Standard systemic therapy
  Standard investigator's choice therapy with systemic chemotherapy and any targeted therapies indicated in the standard clinical practice setting

Primary outcome measures

• Overall survival (OS) [Time frame: Assessed every second month from randomization until study completion, during a maximum of 60 months.]

Secondary outcome measures (8)

• Treatment-related toxicity [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) [Time frame: Assessed at baseline and 2, 4, 6, 12 and 24 months after randomisation]
• Progression free survival (PFS) [Time frame: Assessed from randomization until study completion, during a maximum of 60 months.]
• Radiological response of treatment on ascites present at baseline. [Time frame: Assessed from baseline visit until study completion, during a maximum of 60 months.]
• Paracentesis of ascites [Time frame: Assessed from randomization until study completion, during a maximum of 60 months.]
• Amount of ascites drained [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. [Time frame: Assessed from randomisation until study completion, during a maximum of 60 months.]
• The proportion of patients undergoing conversion surgery [Time frame: Assessed from randomisation until study completion, during a maximum of 60 months.]

Eligibility criteria

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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Open label

Primary purpose

Treatment

Study locations

Sweden · 5 centers

• Sahlgrenska University Hospital — Gothenburg
• Skane University Hospital — Lund
• Örebro University Hospital — Örebro
• Karolinska University Hospital — Stockholm
• Uppsala University Hospital — Uppsala

Italy · 1 center

• Azienda Ospedaliera Universitaria Integrata Verona — Verona

Netherlands · 1 center

• Amsterdam University Medical Center — Amsterdam

Identifiers

NCT: NCT07304271 · 2024-514879-17-00

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗