Adjuvant Pressurized Intraperitoneal Aerosol Chemotherapy to Prevent Colorectal Peritoneal Metastases (ProphyPIPAC)

NCT ID: NCT06091683

Last Updated: 2023-10-19

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2021-04-30
• Study Completion Date: 2025-12-31

Brief Summary

The objective of this clinical trial is to demonstrate the feasibility and safety of pressurized intraperitoneal aerosol chemotherapy (PIPAC) for the prevention of peritoneal metastases after curative-intent surgery for high-risk colorectal cancer.

Detailed Description

This single-arm, single-center, open-label trial enrolls patients after curative-intent surgery for colon adenocarcinoma (proximal to peritoneal reflection), intestinal or mucinous histological type, associated with the following clinical-pathological risk factors for the development of peritoneal metastases: a) stage pT4a, N0-2b, M0 of the Tumor Node Metastasis classification; b) stage pT4b, N0-2b, M0; and c) primary perforated tumor (any T, any N, M0). Eligible patients who will give informed consent undergo laparoscopic pressurized intraperitoneal aerosol chemotherapy (PIPAC) 4 to 8 weeks after primary surgery, followed by adjuvant systemic chemotherapy according to according to current guidelines. After the procedure, patients will be followed-up to assess occurrence of adverse events,survival, peritoneal and systemic disease relapse, and quality of life.

Conditions

Peritoneal Metastases From Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Preliminary laparoscopic exploration of the abdominal cavity and adjuvant pressurized intraperitoneal aerosol chemotherapy (PIPAC) with oxaliplatin and concurrent intravenous infusion of 5-fluorouracil and folinic acid.

Group Type: EXPERIMENTAL

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Intervention Type: PROCEDURE

Laparoscopic exploration of the abdominal cavity with dissection of adhesions and biopsies of suspect findings (if needed).

PIPAC will be administered with oxaliplatin (92 mg/m2 body surface area in 150 ml dextrose solution) for 30 minutes under the following spraying conditions: cytostatic application at a rate of 30 ml/min, pressure of 1380 kilo-pascal over 30 minutes, and temperature of 22°C. One hour before the beginning of PIPAC, intravenous infusion of 5-fluorouracil (400 mg/m2) and folinic acid (20mg/m2) will be initiated. Standard protectionist procedures will be adopted to avoid contamination of operators and the environment with nebulized chemotherapy.

Interventions

Pressurized intraperitoneal aerosol chemotherapy (PIPAC)

Laparoscopic exploration of the abdominal cavity with dissection of adhesions and biopsies of suspect findings (if needed).

PIPAC will be administered with oxaliplatin (92 mg/m2 body surface area in 150 ml dextrose solution) for 30 minutes under the following spraying conditions: cytostatic application at a rate of 30 ml/min, pressure of 1380 kilo-pascal over 30 minutes, and temperature of 22°C. One hour before the beginning of PIPAC, intravenous infusion of 5-fluorouracil (400 mg/m2) and folinic acid (20mg/m2) will be initiated. Standard protectionist procedures will be adopted to avoid contamination of operators and the environment with nebulized chemotherapy.

Intervention Type: PROCEDURE

Eligibility Criteria

Inclusion Criteria

1. Histopathological diagnosis of intestinal type, mucinous or signet ring cell adenocarcinoma of the colon (with upper limit of the tumor above peritoneal reflection);

2. curative (microscopically complete) surgery performed by laparotomy or laparoscopy;

3. presence of at least one of the following risk factors for the development of metachronous peritoneal metastases:

• perforated primary tumor (any T, N0-2b, M0);
• primary tumor infiltrating the visceral peritoneum (pT4a, N0-2b, M0), or directly invading adjacent organs (pT4b, N0-2b, M0);

4. age > 18;

5. performance status 2 according to the World Health Organization score;

6. willingness to start adjuvant systemic chemotherapy and post-operative follow-up;

7. Signing of informed consent.

Exclusion Criteria

1. active sepsis;

2. cardiac function impairment (history of previous heart failure or 40% ejection fraction);

3. renal impairment (serum creatinine >1.5 normal value or creatinine clearance 60 ml/min);

4. liver function impairment (aspartate aminotransferase, alanine aminotransferase, bilirubin > 1.5 normal value);

5. bone marrow function impairment (leukocytes 4000 / mm3, neutrophils 1500 /mm3, platelets 80000/mm3);

6. lung function impairment (diagnosis of severe chronic obstructive pulmonary disease or 50% forced expiratory volume at one second or 40% diffusion capacity of lung for carbon monoxide adjusted for age);

7. extra-abdominal and/or hepatic metastases at the Computed Tomography scan of the chest, abdomen and pelvis with intravenous contrast;

8. severe complications (grade 3-4) after primary cancer surgery;

9. haemorrhagic diathesis or coagulopathy;

10. pregnancy or lactation in progress;

11. psychiatric or neurological conditions such as to preclude protocol procedures; 12) contraindications to laparoscopy; 13) known hypersensitivity to oxaliplatin or other platinum containing compounds and/or to any of their excipients; 14) history of previous malignancies treated in the last three years, excluding cutaneous spinocellular carcinoma and/or basocellular carcinoma; 15) prior pre-operative radio-chemotherapy..

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Dario Baratti, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Istituto Nazionale dei Tumori, Milano, Italy

Locations

Fondazione IRCCS Istituto Nazionale dei Tumori

Milan, , Italy

Site Status: RECRUITING

Countries

Italy

Central Contacts

Dario Baratti, MD

Role: CONTACT

dario.baratti@istitutotumori.mi.it

+390223901 ext. 3441

Facility Contacts

Dario Baratti, MD

Role: primary

dario.baratti@istitutotumori.mi.it

+390223903441

Other Identifiers

2020-000604-11

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

BRI D/17/1DB

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

SC 2020-000604-11_ID_18605

Identifier Type: OTHER

Identifier Source: secondary_id

INT 0068/20

Identifier Type: -

Identifier Source: org_study_id