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Colorectal NeoplasmsPhase 2CRC-PIPACNCT03246321

PIPAC for Peritoneal Metastases of Colorectal Cancer

A Phase 2 study testing repetitive ePIPAC-OX in people with Colorectal Neoplasms and Peritoneal Neoplasms, run by Koen Rovers at 2 sites in Netherlands.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

This is multicentre, open-label, single-arm phase II study that investigates the feasibility, safety, tolerability, preliminary efficacy, costs, and pharmacokinetics or repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC-OX) as a palliative monotherapy for patients with isolated… Read more about this study

Who is it for?
Any age
What is being tested?
repetitive ePIPAC-OX
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
20 participants
Where
2 sitesNetherlands
Study dates
1 Oct 2017to 1 Oct 2019
Phase
Phase 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 Any age
  • All sexes
  • No healthy volunteers
  • Child, Adult, Older adult

Eligible patients are adults who have:

  • a World Health Organisation (WHO) performance status of ≤1;
  • histological or cytological proof of PM of a colorectal or appendiceal carcinoma;
  • unresectable disease determined by abdominal computed tomography (CT) and a diagnostic laparoscopy or laparotomy;
  • adequate organ functions (haemoglobin ≥5.0 mmol/L, neutrophils ≥1.5 x 109/L, platelets ≥100 x 109/L, serum creatinine <1.5 x ULN, creatinine clearance ≥30 ml/min, and liver transaminases <5 x ULN);
  • no symptoms of gastrointestinal obstruction;
  • no radiological evidence of systemic metastases;
  • no contraindications for oxaliplatin or 5-fluorouracil/leucovorin;
  • no contraindications for a laparoscopy;
  • no previous PIPAC-procedures.

Enrolled patients are excluded from the analyses in case they did not receive a first ePIPAC-OX, e.g.:

  • due to systemic metastases on baseline thoracoabdominal CT, or;
  • due to non-access during first ePIPAC-OX, or;
  • due to resectable disease during first ePIPAC-OX.

Importantly, enrolment is allowed for patients with an unresected primary tumour (if asymptomatic) and for patients in various lines of palliative treatment, including patients who refuse, have not had, or do not qualify for first-line palliative systemic therapy. All potentially eligible patients are discussed by a multidisciplinary team. Enrolled patients are informed about the potential consequences of postponing or discontinuing standard palliative treatment by a medical oncologist prior to enrolment.

Trial locations and contacts

2 sites in 1 country.

Netherlands2 sites

  • Catharina Hospital

    Eindhoven

  • St. Antonius Hospital

    Nieuwegein

Other trials in Netherlands

About this study

Official title: Repetitive Electrostatic Pressurised Intraperitoneal Aerosol Chemotherapy With Oxaliplatin (ePIPAC-OX) as a Palliative Monotherapy for Isolated Unresectable Colorectal Peritoneal Metastases: Protocol of a Multicentre, Open-label, Single-arm, Phase II Study (CRC-PIPAC)

This is multicentre, open-label, single-arm phase II study that investigates the feasibility, safety, tolerability, preliminary efficacy, costs, and pharmacokinetics or repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC-OX) as a palliative monotherapy for patients with isolated unresectable colorectal peritoneal metastases.

Read the detailed description

Rationale: repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) is offered as a palliative treatment option for patients with isolated unresectable colorectal peritoneal metastases (PM) in several centres worldwide. However, little is known about its feasibility, safety, tolerability, efficacy, costs, and pharmacokinetics in this setting.

Objectives: to prospectively explore the feasibility, safety, tolerability, preliminary efficacy, costs, and pharmacokinetic profile of repetitive ePIPAC-OX as a palliative monotherapy for isolated unresectable colorectal PM under controlled circumstances.

Study design: multicentre, open-label, single-arm, phase II study.

Setting: two Dutch tertiary referral hospitals for the surgical treatment of colorectal PM.

Study population: adults who have a World Health Organisation (WHO) performance status of 0 or 1, adequate organ functions, histologically or cytologically confirmed unresectable PM of a colorectal or appendiceal carcinoma, no systemic metastases, no symptoms of gastrointestinal obstruction, no contraindications for the planned intervention, and no previous pressurised intraperitoneal aerosol chemotherapy (PIPAC).

Intervention: instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled ePIPAC-OX (92 mg/m2 body-surface area [BSA]) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four weeks after each procedure, patients undergo clinical, radiological, and biochemical evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease progression, after which standard palliative treatment is (re)introduced.

Outcomes: the primary outcome is the number of patients with major toxicity (grade ≥3 according to the Common Terminology Criteria for Adverse Events v4.0) up to four weeks after the last procedure. Secondary outcomes are the environmental safety of ePIPAC-OX, procedure-related characteristics, the number of procedures in each patient and reasons for discontinuation, minor toxicity, organ-specific toxicity, postoperative complications, hospital stay, readmissions, quality of life, costs, progression-free survival, overall survival, and the radiological, histopathological, cytological, biochemical, and macroscopic tumour response. Atomic absorption spectrophotometry is used to measure concentrations of oxaliplatin in plasma, plasma ultrafiltrate, urine, ascites, PM, and normal peritoneum during and after ePIPAC-OX.

Being tested
repetitive ePIPAC-OX
Keywords
Colorectal Neoplasms, Peritoneal Neoplasms, Intraperitoneal Injections, Laparoscopy, Aerosols, Chemotherapy, Cancer, Regional Perfusion, Antineoplastic Agents, Leucovorin, Fluorouracil, Platinum, Intraoperative Complications, Postoperative Complications, Drug-Related Side Effects and Adverse Reactions, Disease-free survival, Survival, Mortality, Quality of Life, Costs and Cost Analysis, Translational Medical Research, Clinical Trials, Phase II as topic
Medical subject headings
Colorectal Neoplasms, Peritoneal Neoplasms, Appendiceal Neoplasms, Neoplasms, Intraoperative Complications, Postoperative Complications, Drug-Related Side Effects and Adverse Reactions, Cecal Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • repetitive ePIPAC-OXCombination product

    Instead of standard palliative treatment, enrolled patients receive laparoscopy-controlled electrostatic pressurised intraperitoneal aerosol chemotherapy with oxaliplatin (ePIPAC-OX) (92 mg/m2 body-surface area [BSA]) with intravenous leucovorin (20 mg/m2 BSA) and bolus 5-fluorouracil (400 mg/m2 BSA) every six weeks. Four weeks after each procedure, patients undergo clinical, radiological, and biochemical evaluation. ePIPAC-OX is repeated until clinical, radiological, or macroscopic disease progression, after which standard palliative treatment is (re)considered.

Study groups in NCT03246321
Study groupRoleWhat they receive
repetitive ePIPAC-OXExperimentalNot described
Receives: Combination Product: repetitive ePIPAC-OX

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Major toxicity

    Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade III-V, up to 4 weeks after the last ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

Secondary outcomes (23)

  1. Minor toxicity

    Number of patients with Common Terminology Criteria for Adverse Events (CTCAE) v4.0 grade II, up to 4 weeks after the last ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  2. Organ-specific toxicity

    Number of patients that develops bone marrow, kidney, or liver function disorders, up to four weeks after the last ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  3. Major postoperative complications

    Number of patients with Clavien-Dindo grade III-V postoperative complications, up to four weeks after the last ePIPAC

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  4. Minor postoperative complications

    Number of patients with Clavien-Dindo grade II postoperative complications, up to four weeks after the last ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  5. Hospital stay

    Number of days between ePIPAC-OX and initial discharge, up to four weeks after the last ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  6. Readmissions

    Number of hospital admissions after initial discharge after ePIPAC-OX, up to four weeks after the last ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  7. Radiological tumour response

    Number of patients with radiological response/stable disease/progression, based on central review of thoracoabdominal CT and diffusion-weighted MRI at baseline and four weeks after each ePIPAC-OX, performed by two independent radiologists blinded to clinical outcomes (classification not defined a priori)

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  8. Histopathological tumour response

    Peritoneal Regression Grading Score (PRGS), based on central review of collected peritoneal biopsies during each ePIPAC-OX, performed by two independent pathologists blinded to clinical outcomes

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

  9. Cytological tumour response

    Number of patients with positive/negative cytology, based on collected ascites or peritoneal washing cytology during each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

  10. Macroscopic tumour response

    Peritoneal Cancer Index and ascites volume during each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

  11. Biochemical tumour response

    Tumour marker value measured at baseline, each postoperative day, and four weeks after each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  12. Quality of life: EQ-5D-5L

    EQ-5D-5L at baseline and one and four weeks after each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  13. Quality of life: QLQ-C30

    QLQ-C30 at baseline and one and four weeks after each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  14. Quality of life: QLQ-CR29

    QLQ-CR29 at baseline and one and four weeks after each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  15. Costs

    Costs of treatment, based on questionnaires (iMTA PCQ, iMTA MCQ) four weeks after each ePIPAC-OX, derived from the Dutch costing guidelines for health care research at the time of analysis

    Measured: Expected (in case of three ePIPAC-OX): 16 weeks

  16. Progression-free survival

    Time between enrolment and clinical, radiological, or macroscopic progression, or death

    Measured: 24 months

  17. Overall survival

    Time between enrolment and death

    Measured: 24 months

  18. Environmental safety of ePIPAC-OX

    Platinum concentrations in the air of the operating room and on the surface of the operating room during ePIPAC-OX

    Measured: 1 week (measured only during the first three procedures in the study)

  19. Pharmacokinetics

    Platinum concentrations in plasma and plasma ultrafiltrate (collected before ePIPAC-OX and 5, 10, 20, 30, 60, 120, 240, 360, and 1080 minutes after oxaliplatin injection), urine (collected before ePIPAC-OX and on postoperative days 1, 3, 5, and 7), and two pieces of normal peritoneum and two peritoneal metastases collected during each ePIPAC-OX.

    Measured: Expected (in case of three ePIPAC-OX): 13 weeks

  20. Procedure-related characteristics: intraoperative complications

    Number of procedures with intraoperative complications determined during each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

  21. Procedure-related characteristics: adhesions

    Zühlke score determined during each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

  22. Procedure-related characteristics: operating time

    Operating time in minutes determined during each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

  23. Procedure-related characteristics: blood loss

    Blood loss in minutes determined during each ePIPAC-OX

    Measured: Expected (in case of three ePIPAC-OX): 12 weeks

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 Aug 2017
  2. Study start1 Oct 2017
  3. Primary completion1 Oct 2019
  4. Study completion1 Oct 2019

Resources

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 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
20 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03246321
Sponsor's protocol ID
NL60405.100.17
Other IDs
2017-000927-29, NTR6603, ISRCTN89947480, NL60405.100.17, 2017
Acronym
CRC-PIPAC
Status last verified
Oct 2019
First submitted
2 Aug 2017
Last updated
15 Oct 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
Yes: Available on request

Publications

  • Giger-Pabst U, Tempfer CB. How to Perform Safe and Technically Optimized Pressurized Intraperitoneal Aerosol Chemotherapy (PIPAC): Experience After a Consecutive Series of 1200 Procedures. J Gastrointest Surg. 2018 Dec;22(12):2187-2193. doi: 10.1007/s11605-018-3916-5. Epub 2018 Aug 21.

    PubMed 30132291

  • Tempfer C, Giger-Pabst U, Hilal Z, Dogan A, Rezniczek GA. Pressurized intraperitoneal aerosol chemotherapy (PIPAC) for peritoneal carcinomatosis: systematic review of clinical and experimental evidence with special emphasis on ovarian cancer. Arch Gynecol Obstet. 2018 Aug;298(2):243-257. doi: 10.1007/s00404-018-4784-7. Epub 2018 Jun 4.

    PubMed 29869089

  • Grass F, Vuagniaux A, Teixeira-Farinha H, Lehmann K, Demartines N, Hubner M. Systematic review of pressurized intraperitoneal aerosol chemotherapy for the treatment of advanced peritoneal carcinomatosis. Br J Surg. 2017 May;104(6):669-678. doi: 10.1002/bjs.10521.

    PubMed 28407227

  • van de Vlasakker VCJ, Lurvink RJ, Wassenaar EC, Rauwerdink P, Bakkers C, Rovers KP, Bonhof CS, Burger JWA, Wiezer MJ, Boerma D, Nienhuijs SW, Mols F, de Hingh IHJT. Comparing patient reported abdominal pain between patients treated with oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy (PIPAC-OX) and primary colorectal cancer surgery. Sci Rep. 2023 Nov 22;13(1):20458. doi: 10.1038/s41598-023-47510-0.

    PubMed 37993560

  • Lurvink RJ, Rovers KP, Wassenaar ECE, Bakkers C, Burger JWA, Creemers GM, Los M, Mols F, Wiezer MJ, Nienhuijs SW, Boerma D, de Hingh IHJT. Patient-reported outcomes during repetitive oxaliplatin-based pressurized intraperitoneal aerosol chemotherapy for isolated unresectable colorectal peritoneal metastases in a multicenter, single-arm, phase 2 trial (CRC-PIPAC). Surg Endosc. 2022 Jun;36(6):4486-4498. doi: 10.1007/s00464-021-08802-6. Epub 2021 Nov 10.

    PubMed 34757489

  • Rovers KP, Wassenaar ECE, Lurvink RJ, Creemers GM, Burger JWA, Los M, Huysentruyt CJR, van Lijnschoten G, Nederend J, Lahaye MJ, Deenen MJ, Wiezer MJ, Nienhuijs SW, Boerma D, de Hingh IHJT. Pressurized Intraperitoneal Aerosol Chemotherapy (Oxaliplatin) for Unresectable Colorectal Peritoneal Metastases: A Multicenter, Single-Arm, Phase II Trial (CRC-PIPAC). Ann Surg Oncol. 2021 Sep;28(9):5311-5326. doi: 10.1245/s10434-020-09558-4. Epub 2021 Feb 5.

    PubMed 33544279

  • Lurvink RJ, Tajzai R, Rovers KP, Wassenaar ECE, Moes DAR, Pluimakers G, Boerma D, Burger JWA, Nienhuijs SW, de Hingh IHJT, Deenen MJ. Systemic Pharmacokinetics of Oxaliplatin After Intraperitoneal Administration by Electrostatic Pressurized Intraperitoneal Aerosol Chemotherapy (ePIPAC) in Patients with Unresectable Colorectal Peritoneal Metastases in the CRC-PIPAC Trial. Ann Surg Oncol. 2021 Jan;28(1):265-272. doi: 10.1245/s10434-020-08743-9. Epub 2020 Jun 22.

    PubMed 32572849

  • Rovers KP, Lurvink RJ, Wassenaar EC, Kootstra TJ, Scholten HJ, Tajzai R, Deenen MJ, Nederend J, Lahaye MJ, Huysentruyt CJ, van 't Erve I, Fijneman RJ, Constantinides A, Kranenburg O, Los M, Thijs AM, Creemers GM, Burger JW, Wiezer MJ, Boerma D, Nienhuijs SW, de Hingh IH. Repetitive electrostatic pressurised intraperitoneal aerosol chemotherapy (ePIPAC) with oxaliplatin as a palliative monotherapy for isolated unresectable colorectal peritoneal metastases: protocol of a Dutch, multicentre, open-label, single-arm, phase II study (CRC-PIPAC). BMJ Open. 2019 Jul 27;9(7):e030408. doi: 10.1136/bmjopen-2019-030408.

    PubMed 31352425

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing repetitive ePIPAC-OX in people with Colorectal Neoplasms and Peritoneal Neoplasms, run by Koen Rovers at 2 sites in Netherlands.

The full registered description is in the About this study section and the official record.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 15 Oct 2019. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Netherlands. 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 phase mean?

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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

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?

Major toxicity (time frame: Expected (in case of three ePIPAC-OX): 16 weeks). 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 NCT03246321, which also lists 8 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 15 Oct 2019.

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