Combined Neoadjuvant Systemic and PIPAC Therapy (NASPIT) for Patients With Colorectal Peritoneal Metastasis Eligible for CRS and HIPEC: A Prospective Phase II Trial

NCT04475159 | Unknown Phase 2 FDA Drug

• 1 other identifier: 6881-20-SMC
• Study Type: interventional
• Target: 50
• Locations: 0 countries
• Sites: N/A

Brief Summary

Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel drug-delivery system developed to deliver, effectively and safely, small doses of cytotoxic agents into peritoneal tumor deposits. It is currently used for palliation and for down-staging of patients who are non-eligible for cytoreductive surgery (CRS) and hyperthermic intra-peritoneal chemotherapy (HIPEC). The aim of this study is to evaluate the efficacy of PIPAC used in neoadjuvant setting to enhance the response of patients with colorectal peritoneal metastasis when combined with neoadjuvant systemic therapy for patients eligible to CRS/HIPEC prior to planned surgery.

Conditions

Metastatic Colorectal Cancer; Peritoneal Carcinomatosis; Colon Adenocarcinoma

Outcome Measures

Primary Outcomes (1)

• Best Overall Response Rates (BORR)

  Clinically, at time of laparoscopic exploration, tumor burden and distribution will be assessed. Peritoneal cancer index (PCI) will be documented. Final evaluation of tumor burden, PCI and clinical response will be evaluated at time of CRS/HIPEC. Radiologically, a baseline abdominal computed tomography (CT) scan will be acquired \<4 weeks before the initiation of the treatment plan and will be repeated before CRS/HIPEC. Response will be evaluated by an independent radiologist as per RECIST criteria 1.1. Pathologically, biopsies from representative lesions will be taken. During the first procedure, before PIPAC delivery one sample from each abdominal quadrant and will be submitted to histopathology examination. Each biopsy site will be marked by a sliver clip for subsequent biopsies in the following PIPAC. Final pathological assessment will be done from specimens obtained at time of cytoreductive surgery .

  12 months after last patient recruitment

Secondary Outcomes (1)

• Recurrence free survival (RFS)

  3 years after the end of the trial

Study Arms (1)

PIPAC arm

EXPERIMENTAL

Together with neoadjuvant systemic therpay PIPAC will be performed twice and regional chemotherpay will be administered before planned CRS/HIPEC

Procedure: Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC)

Interventions

Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC) PROCEDURE

Pressurized Intraperitoneal Aerosol Chemotherapy will be delivered to the abdominal cavity by means of laparoscopy.

PIPAC arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of signed and dated informed consent form
• Stated willingness to comply with all study procedures and availability for the duration of the study and must be willing to return for follow-up
• years of age or older.
• Biopsy (histopathology or cytology) diagnosis of colorectal cancer as defined by the WHO or by cross-sectional imaging reviewed by a board-certified radiologist.
• Good performance status (ECOG \< 2), Karnofski \>60.
• Patients with low or acceptable surgical risk (American Society of Anesthesiology (ASA) score of 3 or less.
• Patient is a candidate for CRS and HIPEC as discussed and recommended by the institutional disease management team (DMT, Tumor Board)
• Patient receiving systemic chemotherapy for up to a maximum of 6 months from peritoneal diagnosis management with stable or responsive disease are eligible for the trial.
• Absolute neutrophil count (ANC) exceeds 1200/mm3, white blood cell count exceeds 4000/mm3 and platelet count is greater than 100,000/mm3
• An international normalized ratio (INR) ≤ 1.5 (patients who are therapeutically anticoagulated for non-related medical conditions such as atrial fibrillation and whose anti-thrombotic treatment can be withheld for operation will be eligible
• Adequate hepatic function must be met as evidenced by total serum bilirubin ≤ 1.5 mg/dl (patients with total bilirubin \> 1.5 mg/dL eligible only with Gilbert's syndrome); alkaline phosphatase \< 2.5 times the upper limit of normal; and, AST less than 1.5 times upper limit of normal \[alkaline phosphatase and AST cannot both exceed the upper limit of normal
• Serum renal functional parameters, BUN and creatinine are within normal limits
• For females of reproductive potential: use of highly effective contraception for at least 1 month prior to screening or with negative pregnancy test at screening.
• Life expectancy of at least six months

You may not qualify if:

• Patients with unresectable (not eligible for CRS/HIPEC) tumors as decided by a multidisciplinary disease management team
• Patients that already received multiple cycles of systemic chemotherapy of more than 6 months and or show progression of disease on systemic therapy.
• Patients with extraperitoneal disease.
• Pregnancy or lactation
• Patients with low performance status (ECOG \> 2 or Karnofski \< 60%)
• Any one or more of the following hematological abnormalities
• Hgb \< 8gm/dl unable to be corrected with transfusion
• Absolute Neutrophil Count \< 1200/mm3
• White blood cell count \< 4000/mm3
• Platelet count \< 100,000/mm3
• INR \> 1.5 (except in patients who are therapeutically AST anticoagulated for non-related medical conditions such as atrial fibrillation and whose anti-thrombotic treatment cannot be withheld for operation will be eligible)
• History of hepatic cirrhosis or present hepatic dysfunction
• Alkaline phosphatase ≥ 2.5 times the upper limit of normal
• ≥ 1.5 times upper limit of normal
• Serum bilirubin \> 1.5 mg/dl (except for patients with Gilbert's syndrome who must have direct bilirubin ≤ 1.0 mg/dl)

Sponsors & Collaborators

• Prof. Aviram Nissan: lead

MeSH Terms

Conditions

Colorectal Neoplasms; Peritoneal Neoplasms; Colonic Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Abdominal Neoplasms; Peritoneal Diseases

Central Study Contacts

Gal Levi, M.Sc

CONTACT

972-3-5307595; gal.levi@sheba.gov.il

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER GOV
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Proffesor

Study Record Dates

• First Submitted: July 14, 2020
• First Posted: July 17, 2020
• Study Start: August 1, 2020
• Primary Completion: August 1, 2022
• Study Completion: August 1, 2023
• Last Updated: July 17, 2020

Record last verified: 2020-07