Study of Efficacy and Safety of Laparoscopic Intra-abdominal Chemotherapy (PIPAC) Performed in Patients With Peritoneal Carcinomatosis From Colorectal, Ovarian, Gastric Cancer and Primary Peritoneal Tumors

NCT ID: NCT02604784

Last Updated: 2020-09-17

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 105 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2015-10-31
• Study Completion Date: 2020-05-31

Brief Summary

Single center, open label, phase I-II, non-randomized, two-cohort, repeated single dose study to explore the feasibility, efficacy, safety, and Overall Response Rate (ORR) of oxaliplatin, or cisplatin and doxorubicin when given as a pressurized intraperitoneal chemotherapy (PIPAC) to patients (men and women) with peritoneal carcinomatosis from ovarian, gastric and colorectal cancers and in primary cancers of peritoneum.

Conditions

Peritoneal Carcinomatosis

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

cohort A

Cohort A: For patients that have indication for systemic therapy with standard chemotherapy. This cohort has a phase II design; the Objective Response Rate (ORR) will be evaluated according to the RECIST criteria (version 1.1) after 2 and 3 cycles of PIPAC with Cisplatin (7.5 mg/m²) + Doxorubicin (1.5 mg/m2 ) or Oxaliplatin (92 mg/m2) according to the primary cancer, in association with standard systemic chemotherapy.

Group Type: EXPERIMENTAL

Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) fixed repeated dose

Intervention Type: DRUG

An open access with a midline 5-6 cm incision is performed and a single-port platform is positioned. A 12 mm Hg CO2 pneumoperitoneum is inflated. PC extent is evaluated according to Peritoneal Cancer Index (PCI) and peritoneal biopsies are taken. A nebulizer is connected to an intravenous high-pressure injector and inserted into the peritoneal cavity; the tightness of the abdomen has to be documented with a CO2 zero-flow. The laparoscopic camera and the nebulizer are maintained in position by a self-retaining retractor (Thompson). A pressurized aerosol containing drugs is delivered. Standard dosage of drugs for each PIPAC: Cisplatin (7.5 mg/m²) + Doxorubicin (1.5 mg/m²) or Oxaliplatin (92 mg/m²) The capnoperitoneum is then maintained for 30 minutes at 37°C. At the end, the aerosol is exsufflated through two sequential micro-particle filters into the air-waste system of the hospital.

cohort B

Cohort B: For patients that have not indication for systemic therapy with standard chemotherapy. This cohort has a phase I design; with a dose-escalation design the maximum tolerated doses and recommended doses of Cisplatin + Doxorubicin and Oxaliplatin (according to the pathology) administered through PIPAC in patients with peritoneal carcinomatosis will be evaluated.

Group Type: EXPERIMENTAL

Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) increasing single dose

Intervention Type: DRUG

An open access with a midline 5-6 cm incision is performed and a single-port platform is positioned. A 12 mm Hg CO2 pneumoperitoneum is inflated. PC extent is evaluated according to Peritoneal Cancer Index (PCI) and peritoneal biopsies are taken. A nebulizer is connected to an intravenous high-pressure injector and inserted into the peritoneal cavity; the tightness of the abdomen has to be documented with a CO2 zero-flow. The laparoscopic camera and the nebulizer are maintained in position by a self-retaining retractor (Thompson). A pressurized aerosol containing drugs is delivered. Escalating dosage of drugs for PIPAC: Cisplatin + Doxorubicin (from 15 mg/m² + 3 mg/m² to 100 mg/m² + 30 mg/m²) or Oxaliplatin (from 92 mg/m² to 300mg/m²).The capnoperitoneum is then maintained for 30 minutes at 37°C. At the end, the aerosol is exsufflated through two sequential micro-particle filters.

Interventions

Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) fixed repeated dose

An open access with a midline 5-6 cm incision is performed and a single-port platform is positioned. A 12 mm Hg CO2 pneumoperitoneum is inflated. PC extent is evaluated according to Peritoneal Cancer Index (PCI) and peritoneal biopsies are taken. A nebulizer is connected to an intravenous high-pressure injector and inserted into the peritoneal cavity; the tightness of the abdomen has to be documented with a CO2 zero-flow. The laparoscopic camera and the nebulizer are maintained in position by a self-retaining retractor (Thompson). A pressurized aerosol containing drugs is delivered. Standard dosage of drugs for each PIPAC: Cisplatin (7.5 mg/m²) + Doxorubicin (1.5 mg/m²) or Oxaliplatin (92 mg/m²) The capnoperitoneum is then maintained for 30 minutes at 37°C. At the end, the aerosol is exsufflated through two sequential micro-particle filters into the air-waste system of the hospital.

Intervention Type: DRUG

Pressurized IntraPeritoneal Air-flow Chemotherapy (PIPAC) increasing single dose

An open access with a midline 5-6 cm incision is performed and a single-port platform is positioned. A 12 mm Hg CO2 pneumoperitoneum is inflated. PC extent is evaluated according to Peritoneal Cancer Index (PCI) and peritoneal biopsies are taken. A nebulizer is connected to an intravenous high-pressure injector and inserted into the peritoneal cavity; the tightness of the abdomen has to be documented with a CO2 zero-flow. The laparoscopic camera and the nebulizer are maintained in position by a self-retaining retractor (Thompson). A pressurized aerosol containing drugs is delivered. Escalating dosage of drugs for PIPAC: Cisplatin + Doxorubicin (from 15 mg/m² + 3 mg/m² to 100 mg/m² + 30 mg/m²) or Oxaliplatin (from 92 mg/m² to 300mg/m²).The capnoperitoneum is then maintained for 30 minutes at 37°C. At the end, the aerosol is exsufflated through two sequential micro-particle filters.

Intervention Type: DRUG

Other Intervention Names

Cisplatin + Doxorubicin in ovarian, gastric cancer and in primary peritoneal tumors; or Oxaliplatin in colorectal cancer; Cisplatin + Doxorubicin in ovarian, gastric cancer and in primary peritoneal tumors; or Oxaliplatin in colorectal cancer

Eligibility Criteria

Inclusion Criteria

• Clinical and pathological confirmation of peritoneal carcinomatosis from gastric, colorectal and ovarian cancers or primary peritoneal tumors.
• Patients aged between 18 and 78 years.
• Performance status sec. ECOG ≤ 2
• Disease progression/relapse after at least one line of previous i.v. standard chemotherapy in gastric cancer and primary peritoneal tumors and two lines in colorectal and ovarian cancers.
• Patients with peritoneal carcinomatosis from ovarian, gastric and colorectal cancers and primary peritoneal cancers not eligible to cytoreductive surgery +/- HIPEC.
• Blood and electrolyte counts, liver, renal and cardiopulmonary function parameters within 10% of the normal range.
• Written informed consent.
• Tumor mass present on CT-scan in order to allow tumor response assessment with RECIST-criteria.

Exclusion Criteria

• Extra-abdominal metastatic disease, with the exception of isolated pleural carcinomatosis.
• Bowel obstruction.
• Severe renal impairment, myelosuppression, severe hepatic impairment, severe myocardial insufficiency, recent myocardial infarction, severe arrhythmias.
• Immunocompromised patients such as those with an immunosuppressive medication or a known disease of the immune system.
• Creatinine clearance < 60 ml /min.
• Pregnancy.
• Previous treatment reaching the maximum cumulative dose of doxorubicin, daunorubicin, epirubicin, idarubicin and/or other anthracyclines and anthracenediones.
• Known allergy to cisplatin or other platinum-containing compounds or to doxorubicin.
• Patients of both sexes who do not conduct complete abstinence from heterosexual relationships or agree to use an effective clinically acceptable method (with failure rate <1%) during the study and the following 6 months after the last treatment.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 78 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione del Piemonte per l'Oncologia

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Department of Surgical Oncology - FPO-IRCCS Institute for Cancer Research and Treatment

Candiolo, Turin, Italy

Countries

Italy

References

Robella M, Berchialla P, Borsano A, Cinquegrana A, Ilari Civit A, De Simone M, Vaira M. Study Protocol: Phase I Dose Escalation Study of Oxaliplatin, Cisplatin and Doxorubicin Applied as PIPAC in Patients with Peritoneal Metastases. Int J Environ Res Public Health. 2021 May 25;18(11):5656. doi: 10.3390/ijerph18115656.

Reference Type: DERIVED

PMID: 34070561 (View on PubMed)

Other Identifiers

015-IRCCS-27F-1

Identifier Type: -

Identifier Source: org_study_id