Normothermic Intraperitoneal Chemotherapy - Long Term in Peritoneal Metastases From Colorectal Cancer (NIPEC-OXA)

Study Overview
=================
Brief Summary
-----------------
Feasibility study regarding 20 Patients with peritoneal metastases from colorectal cancer treated with cytoreductive surgery and HIPEC and subsequently with 4 courses of normothermic intraperitoneal chemotherapy - long term (NIPEC-OXA) with oxaliplatin.

Detailed Description
-----------------
Primary endpoint: to determine if the administration of additional i.p. chemotherapy for a period of 9 weeks after completed CRS and HIPEC is a safe procedure to be used in the future in a formal randomised trial. The toxicity of the chemotherapy given through i.p. during NIPEC-OXA courses will be analysed throughout the entire treatment period and a subsequent 3-month follow-up period. Secondary endpoints: Intra-abdominal chemotherapy drug distribution 7-14 days after CRS and HIPEC and before the 4th NIPEC-OXA course Surgical complications after CRS, HIPEC and NIPEC-OXA until 3 months after the last NIPEC-OXA course Disease-free survival (DFS) Overall survival (OS) Exploratory endpoint: quality of life Estimated date of first patient enrolled: 3rd quarter of 2021 Anticipated recruitment period: 1,5 years Estimated treatment completion date of last patient: 1st quarter of 2023 Expected treatment duration per patient: 9 weeks Expected follow-up period per patient: 3 months after the last NIPEC-OXA procedure

Official Title
-----------------
Normothermic Intraperitoneal Chemotherapy - Long Term in Peritoneal Metastases From Colorectal Cancer - Feasibility Study (NIPEC-OXA)

Conditions
-----------------
Peritoneal Metastases, Colo-rectal Cancer

Intervention / Treatment
-----------------
* Drug: Oxaliplatin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18 - 75 years Able to provide written, informed consent regarding expected cooperation during treatment and follow-up according to ICH GCP, and national/local regulations Histologically verified CRC Histologically verified and/or radiologically/clinically suspected PM from CRC Synchronous or metachronous PM from CRS If neoadjuvant oxaliplatin-containing chemotherapy is administrated, patients with absence of progressive disease (assessed by CT) In metachronous cases: if adjuvant oxaliplatin-containing chemotherapy, the interval between oxaliplatin- containing adjuvant chemotherapy and diagnosis of PM must be >6 months Intraperitoneal tumour burden amenable to CRC and HIPEC with Peritoneal Cancer Index (PCI40) ≤ 20, assessed at the time of surgery Absence of other metastatic sites, i.e. liver, lungs, central lymph nodes Completeness of Cytoreduction (CC) score of 0 is required Eastern Cooperative Oncology Group (ECOG) Performance Status either 0 or 141 Women of childbearing potential (WOCBP), defined as all women physiologically capable of becoming pregnant, should have a negative urine- or serum pregnancy test within 72 hours prior to receiving the 1st dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required. WOCBP should be willing to use 1 highly effective method of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 120 days after the last dose of study medication. Men in a sexual relationship with a WOCBP must agree to use a condom starting with the 1st dose of study therapy through 120 days after the last dose of study therapy. In case of female partner of child-bearing potential, the female partner should use 1 highly effective contraception method as defined in section 5.1.5 - Other considerations. Exclusion Criteria: Has a history of hypersensitivity to oxaliplatin or to any of the excipients listed in the SmPC section 6.1 Has myelosuppression before starting treatment, ie number of neutrophils granulocytes <1.0 x 109/l and/or number of platelets <75 x 109/l Has peripheral sensitive neuropathy with functional outcomes before starting treatment Has severe renal impairment (creatinine clearance < 30 ml min) (see the SmPC section 5.2). Concurrent or previous diagnosis of invasive cancer within 5 years Psychiatric or addictive disorder or other medical condition that would preclude the patient from meeting the trial requirements Participation in another cancer clinical trial Patients who, according to current guidelines will be offered i.v. adjuvant therapy Significant cardiac or other medical illness that would limit activity or survival, such as severe congestive heart failure, unstable angina, or serious cardiac arrhythmia Alcohol or drug abuse Any reason why, in the opinion of the investigator, the patient should not participate Has a known history of Human Immunodeficiency Virus (HIV) Has known active Hepatitis B (e.g., HBsAg reactive) or Hepatitis C (e.g., HCV RNA [qualitative] is detected) Is pregnant or breastfeeding, or expecting to conceive or father children within the project duration of the trial, starting with the screening visit through 120 days after the last dose of trial treatment.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Interventional Model Description: Feasibility study with 20 eligible patients with peritoneal metastases from colorectal cancer
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: NIPEX-OXA arm<br>20 patients treated with NIPEC-OXA after CRS and HIPEC. | Drug: Oxaliplatin<br>* Administration of oxaliplatin intraperitoneally<br>* Other names: Intraperitoneal catheter;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Adverse Events after Intraperitoneal Chemotherapy Administration (NIPEC-OXA) | Common Terminology Criteria for Adverse Events v. 5 | Throughout the entire treatment period, including a 3-month follow-up | 
| Number of Participants with Surgical Complications after CRS, HIPEC and NIPEC-OXA | Clavien-Dindo classification | Throughout the entire treatment period, including a 3-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants with Optimal, Suboptimal and Missing Fluid Distribution in the Abdomen Injected Through 2 I.P. Catheters | CT scans with intraperitoneal contrast | 7-14 days after CRS and HIPEC and before the 4th NIPEC-OXA course | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
NIPEC-LT, Oxaliplatin, CRS, HIPEC