Perioperative Systemic Therapy for Isolated Resectable Colorectal Peritoneal Metastases

Sponsor
Koen Rovers
Study ID
NCT02758951
Phase
PHASE2/PHASE3
Status
Active Not Recruiting

Conditions

  • Colorectal Adenocarcinoma
  • Colorectal Cancer
  • Colorectal Carcinoma
  • Colorectal Neoplasm
  • Colorectal Neoplasms Malignant
  • Peritoneal Cancer
  • Peritoneal Carcinomatosis
  • Peritoneal Metastases
  • Peritoneal Neoplasm Malignant Secondary
  • Peritoneal Neoplasm Malignant Secondary Carcinomatosis
  • Peritoneal Neoplasms

Eligibility Criteria

Sex
ALL
Age
18 Years - N/A
Healthy Volunteers
Not accepted

Interventions

  • Perioperative systemic therapy — OTHER
    Neoadjuvant systemic therapy should start within four weeks after randomisation. Adjuvant systemic therapy should start within twelve weeks after CRS-HIPEC. In case of unacceptable toxicity or contraindications to oxaliplatin or irinotecan in the neoadjuvant setting, CAPOX or FOLFOX may be switched to FOLFIRI and vice versa. In case of unacceptable toxicity or contraindications to oxaliplatin in the adjuvant setting, CAPOX of FOLFOX may be switched to fluoropyrimidine monotherapy. Dose reduction, prohibited concomitant care, permitted concomitant care, and strategies to improve adherence are not specified a priori, but left to the discretion of the treating medical oncologist. Perioperative systemic therapy can be prematurely discontinued due to radiological or clinical disease progression, unacceptable toxicity, physicians decision, or at patients request.
  • Perioperative CAPOX-bevacizumab — COMBINATION_PRODUCT
    Four three-weekly neoadjuvant and adjuvant cycles of CAPOX (130 mg/m2 body-surface area \[BSA\] of oxaliplatin, intravenously \[IV\] on day 1; 1000 mg/m2 BSA of capecitabine, orally twice daily on days 1-14), with bevacizumab (7.5 mg/kg body weight, IV on day 1) added to the first three neoadjuvant cycles.
  • Perioperative FOLFOX-bevacizumab — COMBINATION_PRODUCT
    Six two-weekly neoadjuvant and adjuvant cycles of FOLFOX (85 mg/m2 body-surface area \[BSA\] of oxaliplatin, intravenously \[IV\] on day 1; 400 mg/m2 BSA of leucovorin, IV on day 1; 400/2400 mg/m2 BSA of bolus/continuous 5-fluorouracil, IV on day 1-2), with bevacizumab (5 mg/kg body weight, IV on day 1) added to the first four neoadjuvant cycles.
  • Perioperative FOLFIRI-bevacizumab — COMBINATION_PRODUCT
    Six two-weekly neoadjuvant cycles of FOLFIRI (180 mg/m2 body-surface area \[BSA\] of irinotecan, intravenously \[IV\] on day 1; 400 mg/m2 BSA of leucovorin, IV on day 1; 400/2400 mg/m2 BSA of bolus/continuous 5-fluorouracil, IV on day 1-2) and either four three-weekly (capecitabine (1000 mg/m2 BSA, orally twice daily on days 1-14) or six two-weekly (400 mg/m2 BSA of leucovorin, IV on day 1; 400/2400 mg/m2 BSA of bolus/continuous 5-fluorouracil, IV on day 1-2) adjuvant cycles of fluoropyrimidine monotherapy, with bevacizumab (5 mg/kg body weight, IV on day 1) added to the first four neoadjuvant cycles.
  • CRS-HIPEC, experimental arm — PROCEDURE
    CRS-HIPEC is performed according to the Dutch protocol in all study centres. Until publication of the PRODIGE7 trial, the choice of HIPEC medication (oxaliplatin or mitomycin C) has been left to the discretion of the treating physician, since neither one had a favourable safety or efficacy until then. After publication of the PRODIGE7 trial in 2021, oxaliplatin-based HIPEC was omitted in all centres (and therefore automatically omitted in the present study), and all centres switched to mitomycin C-based HIPEC. CRS-HIPEC should be performed within six weeks after completion of neoadjuvant systemic therapy in case of sufficient clinical condition, and at least six weeks after the last administration of bevacizumab in order to minimise the risk of bevacizumab-related postoperative complications.
  • CRS-HIPEC, control arm — PROCEDURE
    CRS-HIPEC is performed according to the Dutch protocol in all study centres. Until publication of the PRODIGE7 trial, the choice of HIPEC medication (oxaliplatin or mitomycin C) has been left to the discretion of the treating physician, since neither one had a favourable safety or efficacy until then. After publication of the PRODIGE7 trial in 2021, oxaliplatin-based HIPEC was omitted in all centres (and therefore automatically omitted in the present study), and all centres switched to mitomycin C-based HIPEC. CRS-HIPEC should be performed within six weeks after randomisation.

Study Details

This is a multicentre, open-label, parallel-group, phase II-III, superiority study that randomises patients with isolated resectable colorectal peritoneal metastases in a 1:1 ratio to receive either perioperative systemic therapy and cytoreductive surgery with HIPEC (experimental arm) or upfront cytoreductive surgery with HIPEC alone (control arm).

Key Dates

First listed
May 3, 2016
Start date
Jun 1, 2017
Status verified
Mar 2026
Primary completion
Oct 31, 2024
Completion
Jun 1, 2029

Study Design

Enrollment
358 participants (actual)
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT

Arms

  • Experimental: Perioperative systemic therapy and CRS-HIPEC
    At the discretion of the treating physician, perioperative systemic therapy consists of either four 3-weekly neoadjuvant and adjuvant cycles of capecitabine with oxaliplatin (CAPOX), six 2-weekly neoadjuvant and adjuvant cycles of 5-fluorouracil/leucovorin with oxaliplatin (FOLFOX), or six 2-weekly neoadjuvant cycles of 5-fluorouracil/leucovorin with irinotecan (FOLFIRI) followed by either four 3-weekly (capecitabine) or six 2-weekly (5-fluorouracil/leucovorin) adjuvant cycles of fluoropyrimidine monotherapy. Bevacizumab is added to the first three (CAPOX) or four (FOLFOX/FOLFIRI) neoadjuvant cycles. CRS-HIPEC is performed according to the Dutch protocol in all study centres.
  • Active Comparator: Upfront CRS-HIPEC alone
    CRS-HIPEC is performed according to the Dutch protocol in all study centres.

Primary Outcome Measure

Overall survival [ Time Frame: From enrolment up to five years thereafter ]

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