Evaluation of Treatment PERSOnalization Based on Its Therapeutic Monitoring in Patients With Metastatic Colorectal Cancer Treated With REgorafenib

NCT04874207 | Completed Phase 4

• 1 other identifier: 35RC20_9803_RePERSO
• Study Type: interventional
• Target: 110
• Locations: 1 country
• Sites: 9

Brief Summary

Regorafenib has demonstrated a significant benefit in overall survival in metastatic colorectal cancer (mCRC) patients. However, more than 50% of patients had severe adverse events (grade 3-4), leading to temporary or definitive discontinuation of treatment. The RePERSO study proposes to adapt the regorafenib dose regimen taking into account firstly the measurement of sum of metabolites M-2 and M-5 and secondly the occurrence of toxicity during treatment. This treatment personalization through therapeutic drug monitoring pharmacological dosing optimization strategy aims at validating the proof of concept of regorafenib therapeutic drug monitoring and at improving the benefit in OS in patients, using the previously defined Csum therapeutic range.

Conditions

Colorectal Cancer Metastatic

Outcome Measures

Primary Outcomes (1)

• Time from inclusion to death

  Determine whether "optimal exposure" to regorafenib based on plasma concentration of the drug and its metabolites can improve overall survival in mCRC patients

  12 months

Secondary Outcomes (9)

• Ten months survival rate

  10 months

• Objective response Rate

  12 months

• Disease Control Rate

  12 months

• Progression-free survival

  12 months

• Severe toxicities

  12 months

Study Arms (1)

Patients

EXPERIMENTAL

Patients

Drug: Regorafenib

Interventions

Regorafenib DRUG

Dose adaptation at the beginning of cycle 2 and cycle 3 after regorafenib dosage at day 15

Patients

Eligibility Criteria

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

You may qualify if:

• \- Signed and dated informed consent
• Male or female patients ≥ 18 years-old at time of Informed Consent Form (ICF) signature
• Patients must have a histologically proven metastatic colorectal cancer
• Patients who have previously been treated with standard therapy including a fluoropyrimidine, oxaliplatin, irinotecan, an anti-VEGF (bevacizumab or aflibercept) and an anti-EGFR (cetuximab or panitumumab) for patients who had a RAS wild-type tumor
• In mCRC with MSI-H, the patient must have received immunotherapy. For mCRC with BRAF mutation, the patient should have received a BRAF inhibitor if eligible.
• ECOG PS = 0 or 1
• Imaging target greater than one cm must be visible on CT
• Patients must have adequate bone marrow, renal, and hepatic function, as evidenced by the pre-therapeutic check-up performed within 7 days before regorafenib initiation: Normal organ functions as defined below :
• Absolute neutrophil count ≥ 1.3 Giga/L
• Platelets \> 100 Giga/L
• Hemoglobin ≥ 9 g/dL
• Serum creatinine ≤ 1.5 x ULN (Upper Limit of Normal) or Glomerular filtration rate (GFR) ≥30 ml/min/1.73m2 according to the modified Diet in Renal Disease (MDRD) or CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) abbreviated formula
• AST and ALT ≤3 x ULN (≤5.0 × ULN for patients with liver involvement of their cancer)
• Total Bilirubin ≤2 X ULN
• Alkaline phosphatase ≤3 x ULN (≤5 x ULN in patient with liver involvement of their cancer and/or with bone metastases). If Alkaline phosphatase \> 3 ULN (or \>5 ULN in patient with liver involvement of their cancer and/or with bone metastases), hepatic isoenzymes 5-nucleotidase or GGT tests must be performed; hepatic isoenzymes 5-nucleotidase must be within the normal range and/or GGT \< 3 x ULN

You may not qualify if:

• \- Prior treatment with regorafenib, and with any prior antiangiogenic inhibitor except bevacizumab
• Hypersensitivity to the active substance or to any of the excipients
• Systemic cancer therapy with unfinished washout (in general 3 weeks except for example for capecitabin which has a 1 week washout)
• Concomitant treatment with a cytochrome P450 3A4 (CYP3A4) inducer or inhibitor or UGT1A9 inhibitor
• Patients unable to swallow oral medication
• Digestive obstruction, chronic inflammatory bowel disease or any malabsorption condition
• Ongoing uncontrolled infection (viral, bacterial or fungal)
• Known history of human immunodeficiency virus (HIV) infection, active hepatitis B or C or chronic hepatitis B or C requiring treatment with antiviral therapy
• Breastfeeding
• Uncontrolled hypertension (systolic blood pressure \>140 mmHg or diastolic pressure \>90 mmHg despite optimal medical management)
• Arterial thrombotic or embolic events such as cerebrovascular accident (including transient ischemic attacks), within 6 months before the start of study medication
• Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
• Myocardial infarction less than 6 months before the start of study medication
• Any hemorrhage or bleeding event ≥ Grade 3, NCI-CTCAE v 5.0 within 4 weeks prior to the start of study medication
• Major surgical procedure, open biopsy or significant traumatic injury within 28 days before start of study medication

Sponsors & Collaborators

• Rennes University Hospital: lead

Study Sites (9)

CHU Caen

Caen, France

Location

AP-HP Henri Mondor

Créteil, France

Location

Institut Daniel Hollard, Groupe Hospitalier Mutualiste de Grenoble

Grenoble, France

Location

CHU Nantes

Nantes, France

Location

AP-HP St Antoine

Paris, France

Location

Centre Eugène Marquis

Rennes, France

Location

CHU Rennes

Rennes, France

Location

CHU Rouen

Rouen, France

Location

CHU Tours

Tours, France

Location

MeSH Terms

Interventions

regorafenib

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 30, 2021
• First Posted: May 5, 2021
• Study Start: October 22, 2021
• Primary Completion: April 11, 2025
• Study Completion: April 11, 2025
• Last Updated: August 8, 2025

Record last verified: 2025-08

Data Sharing

• IPD Sharing: Will not share

Locations

FR (9)