Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers (PIPOX)

April 19, 2022 updated by: Institut Cancerologie de l'Ouest

Phase I / II Dose Escalation of Oxaliplatin Via a Laparoscopic Approach of Aerosol Pressurized Intraperitoneal Chemotherapy for Nonresectable Peritoneal Metastases of Digestive Cancers (Stomach, Hail and Colorectal)

Current curative treatment of digestive peritoneal carcinomatosis consists of complete cytoreduction surgery associated with intraperitoneal chemotherapy. This treatment has important limits: a high morbimortality and the impossibility of repeating the sessions. The majority of patients are therefore treated with systemic chemotherapy, which despite its progress, remains palliative.

Pressurized Intraperitoneal aerosol chemotherapy (PIPAC) has many advantages: under laparoscopy, low morbidity, good intratumoral penetration of cytotoxics, possibility of repeating the sessions and low financial cost.

Therefore, the investigator propose a phase 1 study, in colorectal and stomach cancer, with oxaliplatin doses escalation in Pressurized Intraperitoneal aerosol chemotherapy. It would allow a better tumor response, with potentially few risks and thus improve survival in patients with digestive peritoneal carcinoses, increasing access to cytoreductive surgery.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

Detailed Description

The objective of this study is to determine the maximum tolerated dose (mtd) of oxaliplatin to be used during PIPAC.

Study design is a phase I/II, multicentre, non-comparative, non-randomised dose escalation clinical trial.

The phase I study will consist of a 3 by 3 dose escalation according to modified fibonacci dose escalation, starting at the current PIPAC dose (i.e. 90mg/m2), up to a maximum dose of 300mg/m2, corresponding to the current Intraperitoneal chemohyperthermia.

Each patient may receive up to 5 PIPAC sessions ; DLT period will be from the first day (D1) of the first PIPAC session until the end of the second PIPAC session, including the interval chemotherapy (i.e. D-1 of the 3rd CIPPA session), i.e. 4 to 6 weeks later ; Phase II study is an extension cohort at the recommended dose determined in the Phase I study. It will be a multi-centre, single-arm study and will analyse overall patient survival and secondary resectability rates with complete cytoreductive surgery and intraperitoneal chemohyperthermia. It will be conducted in approximately 20 patients treated at the recommended dose and followed for 2 years.

Study Type

Interventional

Enrollment (Actual)

34

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Pierre-Bénite, France, 69495
        • Centre Hospitalier Lyon Sud
      • Saint-Herblain, France, 44805
        • Ico Rene Gauducheau
      • Saint-Mandé, France, 94163
        • Hopital Bégin

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

1. Patient age ≥ 18 years 2. Histological or cytological diagnosis or suspicion of peritoneal carcinosis of colorectal, gastric or bowel origin 3. Having previously received at least 3 months of systemic chemotherapy for metastatic disease (type of chemotherapy left to the discretion of each investigator). Patients who received bevacizumab (Avastin®) can be included if and only if the time between the last treatment administered and the first PIPAC received is at least 4 weeks 4. ECOG performance index < or = 2 5. Life expectancy> 3 months 6. Peripheral neuropathy grade ≤ 1 7. Hematological function: Hemoglobin ≥ 9 g / dL, leukocytes ≥ 4000 / mm3, PNN ≥ 1500 / mm3, platelets ≥ 100 000 / mm3 8. Creatinine clearance> 50 mL / min (cockcroft and Gault formula) 9. Hepatic function: Total bilirubin ≤ 1.5 x ULN, ASAT and ALAT ≤ 3 x ULN, Alkaline phosphatases ≤ 3 x ULN 10 . Patients with no known or partial deficiency of Dihydropyrimidine dehydrogenase (i.e. DPD) 11. Effective contraception for women of childbearing age 13. Informing the patient and obtaining free, informed and written consent signed by the patient and his / her investigator.

14. Affiliated subject or beneficiary of the social security scheme.

Exclusion Criteria:

  1. Patients who received bevacizumab (Avastin®) less than 4 weeks ago can not be included
  2. Extra-peritoneal metastases, except for less than 3 pulmonary nodules (each size <5mm)
  3. Known hypersensitivity to Oxaliplatin
  4. Known complete dihydropyrimidine dehydrogenase (i.e. DPD) deficiency
  5. Peripheral neuropathy Grade >1 due to or not with Oxaliplatin previously used
  6. Active or other serious underlying disease that may prevent the patient from receiving treatment
  7. Intracranial or intraocular hypertension (ongoing at the time of inclusion)
  8. Severe or Severe Heart Failure (ongoing at the time of inclusion)
  9. Complete intestinal obstruction (ongoing at the time of inclusion)
  10. Other concurrent cancer or history of cancer other than in situ cancer of treated cervix or basal cell carcinoma or squamous cell carcinoma
  11. Pregnant or nursing women
  12. Persons deprived of their liberty or under guardianship or unable to give their consent
  13. Inability to submit to medical follow-up of the trial for geographical, social or psychological reasons
  14. Long-term corticosteroids (duration> 3 months), except for weaning for at least 3 months

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Oxaliplatin
The experimental drugs used in this protocol are Oxaliplatin, 5-Fluorouracil and L-Folinic acid. All are used as part of their marketing authorization, with the exception of Oxaliplatin as regards its mode of administration specific to the PIPAC procedure (injection and nebulisation in intraperitoneal).
Drug: 5-Fluorouracil
Presentation: Concentrated solution for concentrated infusion in vials containing 250 mg, 500 mg, 1 g and 5 g, in 5 ml, 10 ml, 20 ml and 100 ml respectively, providing a 50 mg / ml solution. Dosage: 400mg / m2. Administration: IV. Day of administration: between 1 h and 24 h before PIPAC.
Drug: L-Folinic acid
Presentation: lyophilisate for parenteral use, dosed at 25 mg, and in the form of a solution for injection by IM or IV dosed at 25 mg / 2.5 ml. Dosage: 20mg / m2. Administration: IV. Day of administration: between 1 h and 24 h before PIPAC.
Other Names:
  • ELVORIN
Drug: Oxaliplatin
Concentrated solution for infusion dosed with 50 mg and 100 mg. Dosage: depending on the dose range assigned to inclusion (from 90mg / m2 to 300mg / m2). Administration: the solution is packaged in a syringe which is subsequently used for injection and not in a conventional bag. The product is administered in a high-pressure injector, during the PIPAC. Day of administration : J1 of PIPAC

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Maximal Tolerated Dose
Time Frame: 8 to 12 weeks
Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)
8 to 12 weeks
Recommanded dose for the extension phase
Time Frame: 8 to 12 weeks
Dose level below the maximum tolerated dose
8 to 12 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level
Time Frame: 24 months after the last PIPAC received
with CTC-AE scale
24 months after the last PIPAC received
Overall survival
Time Frame: 24 months after the last PIPAC received
Median overall survival at the end of the study
24 months after the last PIPAC received
Progression-Free Survival
Time Frame: 12 months after the last PIPAC received
Median PFS, time between the first PIPAC received and progression or death in absence of progression
12 months after the last PIPAC received

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut Cancerologie de l'Ouest

Investigators

  • Principal Investigator: DUMONT Frederic, MD, Institut de Cancérologie de l'Ouest

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

May 24, 2017

Primary Completion (Actual)

February 5, 2019

Study Completion (Actual)

October 1, 2021

Study Registration Dates

First Submitted

September 22, 2017

First Submitted That Met QC Criteria

September 26, 2017

First Posted (Actual)

September 27, 2017

Study Record Updates

Last Update Posted (Actual)

April 25, 2022

Last Update Submitted That Met QC Criteria

April 19, 2022

Last Verified

April 1, 2022

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • ICO-N-2016-03

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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