Digestive CancerPhase 1/2PIPOXNCT03294252
Oxaliplatin in PIPAC for Nonresectable Peritoneal Metastases of Digestive Cancers
A Phase 1/2 study testing 5-Fluorouracil, L-Folinic acid and Oxaliplatin in people with Digestive Cancer, run by Institut Cancerologie de l'Ouest at 3 sites in France.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Digestive Cancer
- What is being tested?
- 5-Fluorouracil, L-Folinic acid and Oxaliplatin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 34 participants
- Where
- 3 sitesFrance
- Study dates
- 24 May 2017to 1 Oct 2021
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
France3 sites
Centre Hospitalier Lyon Sud
Pierre-Bénite, 69495
ICO René Gauducheau
Saint-Herblain, 44805
Hopital Begin
Saint-Mandé, 94163
About this study
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)
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.
- Conditions
- Digestive Cancer
- Being tested
- 5-Fluorouracil, L-Folinic acid, Oxaliplatin
- Keywords
- PIPAC, oxaliplatin, peritoneal metastases
- Medical subject headings
- Gastrointestinal Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
5-FluorouracilDrug
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.
L-Folinic acidDrug
Also called ELVORIN
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.
OxaliplatinDrug
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
| Study group | Role | What they receive |
|---|---|---|
| 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). Receives: Drug: 5-Fluorouracil; Drug: L-Folinic acid; Drug: Oxaliplatin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximal Tolerated Dose
Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)
Measured: 8 to 12 weeks
Recommanded dose for the extension phase
Dose level below the maximum tolerated dose
Measured: 8 to 12 weeks
Secondary outcomes (3)
Cumulative toxicity after the end of the PIPAC sessions received (maximum 5) at the same dose level
with CTC-AE scale
Measured: 24 months after the last PIPAC received
Overall survival
Median overall survival at the end of the study
Measured: 24 months after the last PIPAC received
Progression-Free Survival
Median PFS, time between the first PIPAC received and progression or death in absence of progression
Measured: 12 months after the last PIPAC received
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Sep 2017
- Study start24 May 2017
- Primary completion5 Feb 2019
- Study completion1 Oct 2021
Why it 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.
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Digestive CancerStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 34 participants (actual)
Sponsor and investigators
- Lead sponsor
- Institut Cancerologie de l'Ouest
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- DUMONT Frederic, MD, Principal investigator, Institut de Cancérologie de l'Ouest
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03294252
- Sponsor's protocol ID
- ICO-N-2016-03
- Acronym
- PIPOX
- Status last verified
- Apr 2022
- First submitted
- 22 Sep 2017
- Last updated
- 25 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 33039812Dumont 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
Study at a glance
From the registry record, last updated by the sponsor on 25 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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)
- ClinicalTrials.gov ID
- NCT03294252
- Acronym / sponsor ID
- PIPOX / ICO-N-2016-03
- Conditions
- Digestive Cancer
- Keywords
- PIPAC, oxaliplatin, peritoneal metastases
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- TerminatedReason 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.
- Enrolment
- 34 participants (actual)
- Lead sponsor
- Institut Cancerologie de l'OuestUniversity, hospital or other
- Study start
- 24 May 2017 (actual)
- Primary completion
- 5 Feb 2019 (actual)
- Study completion
- 1 Oct 2021 (actual)
- First posted
- 27 Sep 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Oxaliplatin | Experimental | Drug: 5-Fluorouracil, Drug: L-Folinic acid, Drug: OxaliplatinThe 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). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 5-FluorouracilPresentation: 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 | Oxaliplatin |
| L-Folinic acidAlso: ELVORINPresentation: 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. | Drug | Oxaliplatin |
| OxaliplatinConcentrated 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 | Drug | Oxaliplatin |
Primary outcome
Maximal Tolerated Dose
Time frame: 8 to 12 weeks
Maximal tolerated dose 3x3 patients inclusion(modified fibonacci dose escalation)
Recommanded dose for the extension phase
Time frame: 8 to 12 weeks
Dose level below the maximum tolerated dose
3 secondary outcomes
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
Overall survival
Time frame: 24 months after the last PIPAC received
Progression-Free Survival
Time frame: 12 months after the last PIPAC received
Results and safety
The study was stopped early (reason given: 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.). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Apr 2022.
- Derived from this study: PubMed 33039812Dumont 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.
- Derived from this study: PubMed 30911664Dumont 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
DUMONT Frederic, MD principal investigator
Institut de Cancérologie de l'Ouest
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing 5-Fluorouracil, L-Folinic acid and Oxaliplatin in people with Digestive Cancer, run by Institut Cancerologie de l'Ouest at 3 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 25 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: 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.). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximal Tolerated Dose (time frame: 8 to 12 weeks). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03294252, which also lists 2 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Apr 2022.