PIPAC for Peritoneal Metastases of Colorectal Cancer

NCT03246321 | Completed Phase 2

• 4 other identifiers: NL60405.100.172017-000927-29NTR6603ISRCTN89947480
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 2

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.

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

Outcome Measures

Primary Outcomes (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

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

Secondary Outcomes (23)

• Minor toxicity

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

• Organ-specific toxicity

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

• Major postoperative complications

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

• Minor postoperative complications

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

• Hospital stay

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

Study Arms (1)

repetitive ePIPAC-OX

EXPERIMENTAL

Combination Product: repetitive ePIPAC-OX

Interventions

repetitive ePIPAC-OX COMBINATION_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.

repetitive ePIPAC-OX

Eligibility Criteria

• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

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.

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

• Koen Rovers: lead

Study Sites (2)

Catharina Hospital

Eindhoven, Netherlands

Location

St. Antonius Hospital

Nieuwegein, Netherlands

Location

Related Publications (8)

• 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.

  PMID: 30132291 BACKGROUND

• 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.

  PMID: 29869089 BACKGROUND

• 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.

  PMID: 28407227 BACKGROUND

• 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.

  PMID: 37993560 DERIVED

• 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.

  PMID: 34757489 DERIVED

• 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.

  PMID: 33544279 DERIVED

• 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.

  PMID: 32572849 DERIVED

• 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.

  PMID: 31352425 DERIVED

MeSH Terms

Conditions

Colorectal Neoplasms; Peritoneal Neoplasms; Appendiceal Neoplasms; Neoplasms; Intraoperative Complications; Postoperative Complications; Drug-Related Side Effects and Adverse Reactions; Cecal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Abdominal Neoplasms; Peritoneal Diseases; Cecal Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Chemically-Induced Disorders

Study Officials

• Ignace de Hingh, MD, PhD

  Catharina Hospital, Eindhoven, Netherlands

  STUDY CHAIR

• Djamila Boerma, MD, PhD

  St Antonius Hospital, Nieuwegein, Netherlands

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: MD, Coordinating Investigator

Study Record Dates

• First Submitted: August 2, 2017
• First Posted: August 11, 2017
• Study Start: October 1, 2017
• Primary Completion: October 1, 2019
• Study Completion: October 1, 2019
• Last Updated: October 15, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF, CSR, ANALYTIC CODE
• Time Frame: End of the study
• Access Criteria: Available on request

Locations

NL (2)