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TerminatedNCT03294252PIPOXUpdated Apr 25, 2022

Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers

A Phase 1/2 interventional study of 5-Fluorouracil and L-Folinic acid in Digestive Cancer, sponsored by Institut Cancerologie de l'Ouest. Terminated at 3 sites in France. Open to participants aged 18 Years and older. Per ClinicalTrials.gov, last updated 2022-04-25.

Sponsored by Institut Cancerologie de l'Ouest · Phase 1/2, Interventional, and Treatment

Why this study was terminated
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.
Phase
Phase 1/2
Study type
Interventional
Enrollment
34
Allocation
Not applicable
Ages
18 Years and older
Sex
All
01

Study 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.

Read the 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.

02

Conditions studied

  • Digestive Cancer

Keywords

  • PIPAC
  • oxaliplatin
  • peritoneal metastases
03

Who can participate

Ages eligible
18 Years and older
Sexes eligible
All
Accepts healthy volunteers
No

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

Exclusion criteria

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
04

Study design

Phase
Phase 1 / Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrollment
34 participants (actual)

Study arms

  • 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 · Drug: L-Folinic acid · Drug: Oxaliplatin

Interventions

  • Drug5-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.

  • DrugL-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.

    Also known as: ELVORIN

  • DrugOxaliplatin

    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

05

What researchers measure

Primary outcomes

  1. Maximal Tolerated Dose

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

    Time frame: 8 to 12 weeks

  2. Recommanded dose for the extension phase

    Dose level below the maximum tolerated dose

    Time frame: 8 to 12 weeks

Secondary outcomes

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

    with CTC-AE scale

    Time frame: 24 months after the last PIPAC received

  2. Overall survival

    Median overall survival at the end of the study

    Time frame: 24 months after the last PIPAC received

  3. Progression-Free Survival

    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

06

Study locations

3 sites
  • Centre Hospitalier Lyon Sud
    Pierre-Bénite, 69495, France
  • ICO René Gauducheau
    Saint-Herblain, 44805, France
  • Hopital Begin
    Saint-Mandé, 94163, France
07

References and documents

Publications

  • 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. PubMed 33039812 ↗
  • 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. PubMed 30911664 ↗
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Registry details

Key details

Study ID
NCT03294252
Lead sponsor
Institut Cancerologie de l'Ouest
Responsible party
Sponsor
First posted
Sep 27, 2017
Start date
May 24, 2017
Primary completion
Feb 5, 2019
Completion
Oct 1, 2021
Last update
Apr 25, 2022

Study contacts

DUMONT Frederic, MD
principal investigator · Institut de Cancérologie de l'Ouest

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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