Assessing Safety of NIPOX in Peritoneal Carcinomatosis of CRC

Study Overview
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Brief Summary
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This study determine the maximal tolerate dose

Detailed Description
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This study determine the maximal tolerate dose for the patient treated by intraperitoneal chemotherapy in neoadjuvant treatment of peritoneal carcinomatosis of colorectal origin

Official Title
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Phase I Study Assessing Safety of Intraperitoneal Chemotherapy in Neoadjuvant Treatment of Peritoneal Carcinomatosis of Colorectal Origin

Conditions
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Colorectal Cancer

Intervention / Treatment
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* Drug: Oxaliplatin
* Drug: LV5FU or Folfiri
* Drug: Oxycodone


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients aged over 18 years old Histologically confirmed diagnosis of colorectal or appendix cancer Peritoneal carcinomatosis of colorectal origin, presumed unresecable or non-optimally resecable, assessed by imaging (CT scan (Computed Tomography Scanner) and MRI (Magnetic Resonance Imaging)) or during a previous abdominal surgery Peritoneal Carcinomatosis Index > 17 Previous adjuvant chemotherapy is allowed One or several lines of chemotherapy are allowed Hemoglobin ≥ 10 g/dL (red blood transfusion is allowed if needed), neutrophils ≥ 1.500/mm3, platelets ≥ 100.000/mm3 and white blood cells > 3000 /mm3 Total bilirubin ≤ 1.5 Upper limit of normal (ULN), ALT or AST ≤ 3 ULN Serum creatinine ≤ 1.5 ULN ; Serum calcium ≥ LLN and ≤ 1.2 x UNL ; Serum magnesium ≥ LLN and ≤ 1.2 x UNL ; Kalemia ≥ LLN ECOG (Eastern Cooperative Oncology group) < 1 Life expectancy higher than 8 weeks Negative pregnancy test in women of childbearing potential Use of an effective contraceptive method during the whole treatment and up to 6 months after the completion of treatment Patients affiliated to a French Social Security System Signed informed consent (IC) obtained before any study specific procedures Exclusion Criteria: Serum uracile ≥ 16 ng/ml Extra peritoneal metastatic disease (except ovarian metastases and retroperitoneal nodes) Patients with anesthetic or medical contraindications to surgery Peripheral sensory neuropathy ≥ grade 2 at the time of signing the ICF Patients previously treated with cytoreduction and followed by an intra-peritoneal chemotherapy within the past 6 months. Anticancer therapy (e.g. chemotherapy, radiotherapy, targeted therapy, concomitant systemic immune therapy, or any experimental therapy) within 4 weeks before inclusion History or presence of other cancer within the past 5 years (except adequately treated in situ carcinoma of the cervix and non-melanoma skin cancer) Pregnant or breastfeeding women Known positive test for human immunodeficiency virus (HIV), hepatitis B or C virus or patients with untreated serious infections Participation in another clinical trial within 30 days prior to study entry Legal incapacity or physical, psychological or mental status interfering with the patient's ability to sign the informed consent or to terminate the study ECG with a QT/QTc interval higher than 450 ms for men and higher than 470 ms for women

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Oxaliplatin<br>IP neoadjuvant chemotherapy protocol: Oxaliplatine will be administered in IP in a total solution of 2L of serum G5%. A continuous infusion pump of Oxycodone would be administered for the entire duration of the intraperitoneal chemotherapy. Perfusion time for the intraperitoneal chemotherapy is estimated but not limited to one and a half hour. Intravenous chemotherapy protocol: Associated Intravenous (systemic) chemotherapy is administered during IP chemotherapy including at least LVFU2 (5FU-Leucovorin) or FOLFIRI (5FU-Irinotecan) regimens and targeted therapy if needed. | Drug: Oxaliplatin<br>* Dose levels of Oxaliplatin: 4 dose levels of Oxaliplatin (85, 100, 130 and 160 mg/m²) are planned. 1 dose level is planned (-1 : 70 mg/m²) if DLT is reached at level 1 Table 1: Dose levels Dose Level Dose (mg/m²) Number of patients DL -1 70 mg 3-6 DL 1 * 85 mg 3-6 DL 2 100 mg 3-6 DL 3 130 mg 3-6 DL 4 160 mg 3-6 * Start level<br>Drug: LV5FU or Folfiri<br>* Association of chemotherapy by LV5FU or Folfiri according pratician choice<br>Drug: Oxycodone<br>* Oxycodone<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Maximum tolerated dose | To determine: - Maximum tolerated dose (MTD), | through study completion, an average of 3 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Area Under the Curve (AUC) | To evaluate Long term pharmacokinetic profile of associated targeted agents in tumoral tissue | through study completion, an average of 3 year |