Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers

NCT03294252 | Terminated Phase 1

• 1 other identifier: ICO-N-2016-03
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 3

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.

Conditions

Digestive Cancer

Keywords

PIPAC; oxaliplatin; peritoneal metastases

Outcome Measures

Primary Outcomes (2)

• Maximal Tolerated Dose

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

  8 to 12 weeks

• Recommanded dose for the extension phase

  Dose level below the maximum tolerated dose

  8 to 12 weeks

Secondary Outcomes (3)

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

  24 months after the last PIPAC received

• Overall survival

  24 months after the last PIPAC received

• Progression-Free Survival

  12 months after the last PIPAC received

Study Arms (1)

Oxaliplatin

EXPERIMENTAL

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

5-Fluorouracil DRUG

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.

Oxaliplatin

L-Folinic acid DRUG

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

Oxaliplatin

Oxaliplatin DRUG

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

Oxaliplatin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \. 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.
• \. Affiliated subject or beneficiary of the social security scheme.

You may not qualify if:

• 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
• 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

Sponsors & Collaborators

• Institut Cancerologie de l'Ouest: lead

Study Sites (3)

Centre Hospitalier Lyon Sud

Pierre-Bénite, 69495, France

Location

ICO René Gauducheau

Saint-Herblain, 44805, France

Location

Hopital Begin

Saint-Mandé, 94163, France

Location

Related Publications (2)

• 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.

  PMID: 33039812 DERIVED

• 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.

  PMID: 30911664 DERIVED

MeSH Terms

Conditions

Gastrointestinal Neoplasms

Interventions

Fluorouracil; Leucovorin; Oxaliplatin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Coenzymes; Enzymes and Coenzymes; Coordination Complexes; Organic Chemicals

Study Officials

• DUMONT Frederic, MD

  Institut de Cancérologie de l'Ouest

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 22, 2017
• First Posted: September 27, 2017
• Study Start: May 24, 2017
• Primary Completion: February 5, 2019
• Study Completion: October 1, 2021
• Last Updated: April 25, 2022

Record last verified: 2022-04

Locations

FR (3)