Clinical trial NCT03246321: PIPAC for Peritoneal Metastases of Colorectal Cancer
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)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Neoplasms
Peritoneal Neoplasms
Appendiceal Neoplasms
Peritoneal Carcinomatosis
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
PIPAC
Pressurized Intraperitoneal Aerosol Chemotherapy
Pressurised Intraperitoneal Aerosol Chemotherapy
Peritoneum
Cecal Neoplasms
Oxaliplatin
Lead sponsor: Catharina Ziekenhuis Eindhoven
Sponsor class: OTHER
First posted: 2017-08-11
Enrollment: 20
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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 unresectable colorectal peritoneal metastases.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Major toxicity
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
Secondary outcomes:
measure: Minor toxicity
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Organ-specific toxicity
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Major postoperative complications
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Minor postoperative complications
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Hospital stay
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Readmissions
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Radiological tumour response
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Histopathological tumour response
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
measure: Cytological tumour response
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
measure: Macroscopic tumour response
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
measure: Biochemical tumour response
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Quality of life: EQ-5D-5L
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Quality of life: QLQ-C30
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Quality of life: QLQ-CR29
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Costs
timeFrame: Expected (in case of three ePIPAC-OX): 16 weeks
measure: Progression-free survival
timeFrame: 24 months
measure: Overall survival
timeFrame: 24 months
measure: Environmental safety of ePIPAC-OX
timeFrame: 1 week (measured only during the first three procedures in the study)
measure: Pharmacokinetics
timeFrame: Expected (in case of three ePIPAC-OX): 13 weeks
measure: Procedure-related characteristics: intraoperative complications
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
measure: Procedure-related characteristics: adhesions
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
measure: Procedure-related characteristics: operating time
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
measure: Procedure-related characteristics: blood loss
timeFrame: Expected (in case of three ePIPAC-OX): 12 weeks
Other outcomes:
Locations:
city: Eindhoven
country: Netherlands
facility: Catharina Hospital
city: Nieuwegein
country: Netherlands
facility: St. Antonius Hospital
Study officials:
affiliation: Catharina Hospital, Eindhoven, Netherlands
name: Ignace de Hingh, MD, PhD
role: STUDY_CHAIR
affiliation: St Antonius Hospital, Nieuwegein, Netherlands
name: Djamila Boerma, MD, PhD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.
citation: 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.
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citation: 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.
citation: 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.
citation: 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.