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

Primary Purpose

Digestive Cancer

Status

Terminated

Phase

Phase 1

Locations

France

Study Type

Interventional

Intervention

5-Fluorouracil

L-Folinic acid

Oxaliplatin

About this trial

This is an interventional treatment trial for Digestive Cancer focused on measuring PIPAC, oxaliplatin, peritoneal metastases

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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:

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

Sites / Locations

Centre Hospitalier Lyon Sud
ICO René Gauducheau
Hopital Begin

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Oxaliplatin

Arm Description

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).

Outcomes

Primary Outcome Measures

Maximal Tolerated Dose

Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)

Recommanded dose for the extension phase

Dose level below the maximum tolerated dose

Secondary Outcome Measures

Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level

with CTC-AE scale

Overall survival

Median overall survival at the end of the study

Progression-Free Survival

Median PFS, time between the first PIPAC received and progression or death in absence of progression

Full Information

NCT ID

NCT03294252

First Posted

September 22, 2017

Last Updated

April 19, 2022

Sponsor

Institut Cancerologie de l'Ouest

1. Study Identification

Unique Protocol Identification Number

NCT03294252

Brief Title

Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers

Acronym

PIPOX

Official Title

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)

Study Type

Interventional

2. Study Status

Record Verification Date

April 2022

Overall Recruitment Status

Terminated

Why Stopped

The 34 patients included had all completed their treatment period under the protocol and the data could be collected to assess the main objective and the secondary objectives before the last theoretical follow-up.

Study Start Date

May 24, 2017 (Actual)

Primary Completion Date

February 5, 2019 (Actual)

Study Completion Date

October 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Institut Cancerologie de l'Ouest

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

Brief Summary

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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Digestive Cancer

Keywords

PIPAC, oxaliplatin, peritoneal metastases

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1, Phase 2

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

34 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Oxaliplatin

Arm Type

Experimental

Arm Description

Intervention Type

Drug

Intervention Name(s)

5-Fluorouracil

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

L-Folinic acid

Other Intervention Name(s)

ELVORIN

Intervention Description

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.

Intervention Type

Drug

Intervention Name(s)

Oxaliplatin

Intervention Description

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

Primary Outcome Measure Information:

Title

Maximal Tolerated Dose

Description

Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)

Time Frame

8 to 12 weeks

Title

Recommanded dose for the extension phase

Description

Dose level below the maximum tolerated dose

Time Frame

8 to 12 weeks

Secondary Outcome Measure Information:

Title

Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level

Description

with CTC-AE scale

Time Frame

24 months after the last PIPAC received

Title

Overall survival

Description

Median overall survival at the end of the study

Time Frame

24 months after the last PIPAC received

Title

Progression-Free Survival

Description

Median PFS, time between the first PIPAC received and progression or death in absence of progression

Time Frame

12 months after the last PIPAC received

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

DUMONT Frederic, MD

Organizational Affiliation

Institut de Cancérologie de l'Ouest

Official's Role

Principal Investigator

Facility Information:

Facility Name

Centre Hospitalier Lyon Sud

City

Pierre-Bénite

ZIP/Postal Code

69495

Country

France

Facility Name

ICO René Gauducheau

City

Saint-Herblain

ZIP/Postal Code

44805

Country

France

Facility Name

Hopital Begin

City

Saint-Mandé

ZIP/Postal Code

94163

Country

France

12. IPD Sharing Statement

Citations:

PubMed Identifier

33039812

Citation

Dumont F, Passot C, Raoul JL, Kepenekian V, Lelievre B, Boisdron-Celle M, Hiret S, Senellart H, Pein F, Blanc-Lapierre A, Raimbourg J, Thibaudeau E, Glehen O; BIG-RENAPE Networks. A phase I dose-escalation study of oxaliplatin delivered via a laparoscopic approach using pressurised intraperitoneal aerosol chemotherapy for advanced peritoneal metastases of gastrointestinal tract cancers. Eur J Cancer. 2020 Nov;140:37-44. doi: 10.1016/j.ejca.2020.09.010. Epub 2020 Oct 8.

Results Reference

derived

PubMed Identifier

30911664

Citation

Dumont F, Senellart H, Pein F, Campion L, Glehen O, Goere D, Pocard M, Thibaudeau E. Phase I/II study of oxaliplatin dose escalation via a laparoscopic approach using pressurized aerosol intraperitoneal chemotherapy (PIPOX trial) for nonresectable peritoneal metastases of digestive cancers (stomach, small bowel and colorectal): Rationale and design. Pleura Peritoneum. 2018 Sep 15;3(3):20180120. doi: 10.1515/pp-2018-0120. eCollection 2018 Sep 1.

Results Reference

derived

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Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers

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