Trial assessing a regorafenib-irinotecan combination (REGIRI) versus regorafenib alone in metastatic colorectal cancer patients after failure of standard therapies.

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Regional Du Cancer De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

18 Sep 2019 → ongoing

Decision date (initial)

2024-07-02

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

DGOS

External identifiers

EU CT number

2024-512555-21-00

EudraCT number

2018-002231-24

ClinicalTrials.gov

NCT03829462

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy

Comparison of overall survival in the Regorafenib and REGIRI combination (Regorafenib + Irinotecan) arms in mCRC patients of Cyclin D1 A/A genotype.

Secondary objectives 6

1. Progression-free survival
2. Time to deterioration
3. Objective response rate
4. Disease control rate according to Recist criteria (version 1.1)
5. Toxicity (according to the NCI-CTCAE v5.0)
6. Quality of life (EORTC QLQ-C30)

Conditions and MedDRA coding

Metastatic colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Histological documentation of adenocarcinoma of the colon or rectum
2. Patients with metastatic colorectal cancer
3. Progression during or within 3 months following the last administration of approved standard therapies, which must include a fluoropyrimidine (or raltitrexed), oxaliplatin, irinotecan, anti-VEGF therapy and an anti-EGFR therapy (for RAS wild-type tumors), encorafenib
4. ECOG performance status ≤1
5. Life expectancy of at least 3 months
6. Patients with A/A CCND1 genotype of rs603965 CCND1
7. International normalized ratio (INR) ≤ 1.5 x ULN and partial thromboplastin time (PTT) or activated partial thromboplastin time (aPTT) ≤ 1.5 x ULN unless receiving treatment with therapeutic anticoagulation. Patients being treated with anticoagulant, e.g., heparin, will be allowed to participate provided no prior evidence of an underlying abnormality in these parameters exists. Close monitoring of at least weekly evaluations will be performed until INR and PTT are stable based on a pre-dose measurement as defined by the local standard of care

Exclusion criteria 29

1. Patients with A/G or G/G CCND1 genotype of rs603965 CCND1
2. Prior treatment with regorafenib or sorafenib
3. Prior treatment with TAS 102
4. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days before start of study drug
5. Pregnant or breast-feeding subjects. Women of childbearing potential must have a pregnancy test performed a maximum of 7 days before start of treatment, and a negative result must be documented before start of study drug
6. Congestive heart failure ≥ New York Heart Association (NYHA) class 2
7. Unstable angina (angina symptoms at rest), new-onset angina (begun within the last 3 months)
8. Myocardial infarction less than 6 months before start of study drug
9. Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted)
10. Uncontrolled hypertension. (Systolic blood pressure > 140 mmHg or diastolic pressure > 90 mmHg despite optimal medical management)
11. Pleural effusion or ascites that causes respiratory compromise (≥ NCI-CTCAE V5.0 Grade 2 dyspnea)
12. Ongoing infection > Grade 2 NCI-CTCAE V5.0
13. Known history of human immunodeficiency virus (HIV) infection
14. Active hepatitis B or C, or chronic hepatitis B or C requiring treatment with antiviral therapy
15. Patients with seizure disorder requiring medication
16. History of organ allograft
17. Patients with evidence or history of any bleeding diathesis, irrespective of severity
18. Any hemorrhage or bleeding event ≥ NCI-CTC V5.0 Grade 3 within 4 weeks prior to the start of study medication
19. Non-healing wound, ulcer, or bone fracture
20. Dehydration NCI-CTCAE V5.0 Grade ≥ 1
21. Known hypersensitivity to any of the study drugs, study drug classes, or excipients in the formulation
22. Persistent proteinuria of NCI-CTCAE V5.0 Grade 3 (> 3.5g/24 hours)
23. Patients unable to swallow oral medications
24. Any malabsorption condition
25. Chronic inflammatory bowel disease and / or bowel obstruction
26. Unresolved toxicity higher than NCI-CTCAE V.5.0 Grade 1 attributed to any prior therapy/procedure excluding alopecia, hypothyroidism and oxaliplatin induced neurotoxicity ≤ Grade 2
27. Concomitant intake of St. John's wort
28. History of gastrointestinal fistula or perforation
29. Previous or concurrent cancer that is distinct in primary site or histology from colorectal cancer within 5 years prior to study inclusion, except for curatively treated cervical cancer in situ, non-melanoma skin cancer and superficial bladder tumors [Ta (non invasive tumor), Tis (carcinoma in situ) and T1 (lamina propria invasion)].

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival presented with its median and confidence interval at 95%, estimated from randomization date to the date of death, whatever the cause, using the Kaplan-Meier method.

Secondary endpoints 6

1. Progression-free survival (PFS)
2. Time to Deterioration
3. Disease control rate
4. Objective response rate
5. Safety according version 5 of NCI-CTCAE
6. Quality of life (EORTC QLQ-C30)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Regional Du Cancer De Montpellier

Sponsor organisation

Institut Regional Du Cancer De Montpellier

Address

208 Avenue Des Apothicaires

City

Montpellier Cedex 5

Postcode

34298

Country

France

Scientific contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Project manager

Public contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Project manager

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 3 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications