Phase III study in mCRC patients with RAS/BRAF wild type tissue and RAS/BRAF mutated in LIquid BIopsy to compare in first-line therapy FOLFIRI plus CetuxiMAb or BevacizumaB

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Azienda USL IRCCS Di Reggio Emilia

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

1 Dec 2024 → ongoing

Decision date (initial)

2024-11-11

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

AIFA

External identifiers

EU CT number

2024-517863-22-00

EudraCT number

2020-005078-82

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy, Prophylaxis, Therapy

The primary objective of the study is to assess whether the combination of bevacizumab plus chemotherapy is superior to cetuximab plus chemotherapy in terms of PFS in patients with RAS/BRAF mut at liquid biopsy and RAS/BRAF wt on tissue

Secondary objectives 6

1. to assess whether the combination of bevacizumab plus chemotherapy is superior to cetuximab plus chemotherapy in terms of Overall survival (OS)
2. to assess whether the combination of bevacizumab plus chemotherapy is superior to cetuximab plus chemotherapy in terms of Objective response rate (ORR)
3. to describe the prevalence of mutation of RAS/BRAF evaluated at liquid biopsy in a population of mCRC with RAS/BRAF wild type on tumor tissue
4. to describe the safety of the two treatment arms
5. to describe the compliance of the two treatment arms
6. to describe the prevalence of mutation of RAS/BRAF evaluated at liquid biopsy in a population of mCRC with RAS/BRAF wild type on tumor tissue

Conditions and MedDRA coding

Study population consists in patients with a diagnosis of mCRC who have never received systemic treatment for advanced/metastatic disease and who are candidate to receive a first line therapy with FOLFIRI plus cetuximab or bevacizumab

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 12

1. Provision of written informed consent
2. Male or female > 18 years of age
3. Histologically confirmed diagnosis of colorectal adenocarcinoma RAS/BRAF wild type (analysed either on primary and/or related metastasis)
4. Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease
5. Patients suitable for first line chemotherapy
6. Life expectancy > 3 months
7. At least one site of measurable disease per RECIST 1.1
8. ECOG Performance status ≤ 2
9. Adequate bone marrow, liver and renal function assessed before starting study treatment
10. If DPD status is known it must be wild type. No restrictions are applied if DPD status in unknown
11. Women of childbearing potential must have a negative blood pregnancy test within 24 hr prior to the start of study treatment. For this trial, women of childbearing potential are defined as all women after puberty, unless they are postmenopausal for at least 12 months, are surgically sterile, or are sexually inactive
12. Subjects and their partners must be willing to avoid pregnancy during the trial and until 5 months for WOCBP (Women of Childbearing Potential) and 7 months for male subjects with female partners of WOCBP after the last trial treatment. Male subjects with female partners of childbearing potential and female subjects of childbearing potential must, therefore, be willing to use adequate contraception as approved by the investigator (barriers contraceptive measure or oral contraception)

Exclusion criteria 18

1. Previous chemotherapy treatment, with the exception of patient treated in adjuvant setting completed at least 6 months before the randomization
2. Any contraindication to the use of Cetuximab, Bevacizumab, Irinotecan, 5FU or folinic acid
3. Radiotherapy to any site within 4 weeks before the randomization
4. Serious, non-healing wound, ulcer, or bone fracture
5. Evidence of bleeding diathesis or coagulopathy
6. Uncontrolled hypertension and prior history of hypertensive crisis or hypertensive encephalopathy
7. Additional malignancy in the last 5 years. Exceptions include basal cell carcinoma of the skin, squamous cell carcinoma of the skin, or in situ cervical cancer that has undergone potentially curative therapy
8. Active and untreated brain (CNS) metastases and/or carcinomatous meningitis
9. Active infection requiring systemic therapy or active disseminated intravascular coagulation
10. History of Human Immunodeficiency Virus (HIV) (HIV 1/2 antibodies)
11. Any positive test for hepatitis B or hepatitis C virus indicating acute or chronic infection
12. Chronic, daily treatment with high-dose aspirin (>325 mg/day)
13. Any previous venous thromboembolism > NCI CTCAE Grade 3
14. History of abdominal fistula, GI perforation, intra-abdominal abscess or active GI bleeding within 6 months prior to the first study treatment. History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
15. Current, recent (within 10 days prior to study treatment start) or ongoing treatment with anticoagulants for therapeutic purposes. Patients with an active therapy with low molecular weight heparin or NAO may be enrolled
16. Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study treatment start, or anticipation of the need for major surgical procedure during the course of the study
17. History of any severe hypersensitivity reactions to any monoclonal antibody
18. A significant concomitant disease which, in the investigating physician's opinion, rules out the patient’s participation in the study

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. The primary endpoint will be PFS

Secondary endpoints 5

1. Overall survival
2. Objective Response Rate
3. Prevalence of RAS/BRAF mutation
4. Safety
5. Compliance

Investigational products

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

Test 1

Comparator 1

Auxiliary 3

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Azienda USL IRCCS Di Reggio Emilia

Sponsor organisation

Azienda USL IRCCS Di Reggio Emilia

Address

Viale Risorgimento 80

City

Reggio Emilia

Postcode

42123

Country

Italy

Scientific contact point

Organisation

Azienda USL IRCCS Di Reggio Emilia

Contact name

Azienda USL IRCCS Di Reggio Emilia

Public contact point

Organisation

Azienda USL IRCCS Di Reggio Emilia

Contact name

Azienda USL IRCCS Di Reggio Emilia

Third parties 1

Locations

1 EU/EEA country · 84 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 15 files

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

Application history

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