PRODIGE 115 (FFCD 2406) ULYSSE : FOLFOX/FOLFIRI + Bévacizumab ou Fruquintinib en 2ème ligne du Cancer Colorectal métastatique (CCRm) : essai de phase II randomisée non comparative ULYSSE (PRODIGE 115 – FFCD 2406)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Fondation Franc.Cancerologie Digestive

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Digestive System Diseases [C06]

Trial duration

19 Feb 2026 → ongoing

Decision date (initial)

2025-10-08

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

TAKEDA

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Disease Control Rate (DCR) assessed 4 months after the start of treatment

Secondary objectives 7

1. Treatment tolerability and safety
2. Progression Free Survival (PFS) per RECIST v1.1 as assessed by the investigator
3. Objective Response Rate (ORR) per RECIST v1.1 as assessed by the investigator
4. Duration Of Response (DOR) per RECIST v1.1 as assessed by the investigator
5. Overall Survival (OS)
6. Quality of life (QLQ-C30)
7. Time to OMS degradation >2

Conditions and MedDRA coding

métastatique colorectal cancer

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 18

1. Age ≥ 18 years and ≤ 80 years; provided the score of the G8 geriatric questionnaire is >14 for patients 75 years or older
2. Adequate hematological (Hemoglobin ≥10g/dL, platelets ≥100G/L, neutrophils ≥1.5G/L) and renal (creatinine clearance ≥ 50 mL/min according to CKD-EPI) functions
3. Proteinuria < 2+ (dipstick urinalysis) (if 2+ or more, proteinuria must be ≤1g/24hour)
4. Life expectancy ≥ 3 months
5. Women of childbearing potential must agree to use a highly effective method of contraception during the trial and for at least 15 months after discontinuation of the experimental treatments. Men who have sexual relations with women of childbearing potential must agree to use contraception during treatment and for at least 12 months after discontinuation of the experimental treatments
6. Ability of the patient to understand, sign and date the information note and informed consent form before any study specific procedures
7. Patient affiliated to a social security scheme
8. Available tumor sample and pathology report for collection
9. Patients with a histologically confirmed diagnosis of metastatic colorectal cancer (mCRC), with a documented disease progression (as per RECIST v1.1, assessed by the investigator and confirmed through CT or MRI).
10. Patients must have previously received first-line therapy with Bevacizumab or an EGFRi, in combination with either FOLFOX or FOLFIRI, for non-resectable mCRC. Patients who progressed during the adjuvant chemotherapy (FOLFOX) or within the 6 months following its completion are eligible for inclusion
11. Patients must have an unresectable tumor at the time of enrollment
12. Patients must have at least one measurable/evaluable metastatic lesion according to RECIST v1.1 criteria; images have to be available for collection
13. Metastases not amenable to surgery and/or thermo-ablation and/or stereotaxic radiotherapy
14. WHO performance status 0 or 1
15. Available parameters to compute the SPOD score: WHO PS, hemoglobin, platelet count, WBC/absolute neutrophil count ratio, lactate dehydrogenase (LDH), alkaline phosphatase, and the number of metastatic sites.
16. Adequate liver functions: Total Bilirubinemia < 1,5 ULN, AST and ALT ≤ 3 ULN
17. BRAF V600E wild type tumor
18. MSS/pMMR tumor

Exclusion criteria 32

1. Patients who have received more than one prior systemic therapy
2. Hypersensitivity to one of the study drugs or one of its excipients
3. Inability to swallow capsules
4. Live attenuated vaccines 30 days prior to treatment start
5. Untreated bone fracture
6. Significant haemorrhagic diathesis or coagulopathy (in the absence of anti-coagulant treatment)
7. Major surgery, open biopsy or major traumatic lesion in the prior 30 days, or the need for major surgery during the trial
8. Pregnant or breastfeeding woman or patients with no adequate contraception
9. Known Uridine Diphosphate Glucuronyltransferase (UGT1A1) deficiency or known Gilbert disease
10. Strong inducers of CYP3A4 (treatment with St John’s Wort (Hypericum perforatum), fampicin, phenobarbital, primidone, phenytoin and carbamazepine)
11. Strong inhibitors of CYP3A4, continuous use of azole antifungals (posaconazole, voriconazole, itraconazole, isavuconazole), ritonavir, verapamil, diltiazem, grapefruit juice (equivalent to half a fresh grapefruit/day)
12. FOLFIRINOX Regimen +/- targeted therapy in the first line setting
13. Concomitant or recent treatment with sorivudine or its analogs (including brivudine) within 4 weeks prior to the administration of protocol treatment (related to Fluorouracil)
14. QT/QTc interval > 450 ms for men and > 470 ms for women
15. Uncontrolled hypertension (defined as systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg) or history of hypertensive crisis (TA systolic> 20 mmHg) or hypertensive encephalopathy
16. History of veinous thromboembolic events, including deep vein thrombosis and pulmonary embolism, within the past month prior to study enrollment
17. History of stroke and/or transient ischemic attack (TIA) within the past 12 months
18. Persistent toxicities related to prior treatment of grade greater than 1
19. Persistence of clinically significant symptoms after a thromboembolic event despite anticoagulant treatment
20. Arterial thromboembolism (myocardial infarction, stroke, transient ischemic attack) occurring under antiangiogenic therapy
21. Other active cancers or history of cancer treated within the last 5 years except for carcinoma in situ of the cervix or basal cell or squamous cell skin carcinoma or any other carcinoma in situ, considered cured
22. Unknown RAS status
23. Persons deprived of liberty or under guardianship or unable of giving consent
24. Inability to undergo the medical follow-up of the trial for geographical, social or psychological reasons
25. Known brain metastasis
26. Known peritoneal carcinomatosis if there are signs of clinical occlusion or sub-occlusion
27. History of gastric ulceration, or myocardial infarction, or severe coronaropathy or severe cardiac dysfunction, within the past 6 months prior to treatment start
28. Patients with dihydropyrimidine dehydrogenase deficiency (uracilemia ≥ 16 ng/mL)
29. According the SmPC of bevacizumab: hypersensitivity to Chinese Hamster Ovary (CHO) cell products or other recombinant human or humanised antibodies; gastrointestinal perforation
30. According the SmPC of irinotecan, in case of chronic inflammatory bowel disease and/or bowel obstruction,
31. According the SmPC of oxaliplatine: in case of peripheral sensory neuropathy with functional impairment prior to first treatment, in case of hypokalemia, hypomagnesemia or hypocalcemia, given the cardiotoxicity of treatment with oxaliplatin (risk of prolongation of QT [see section 4.4. of oxaliplatin SmPC])
32. According to section 4.3 of the SmPC of 5-fluorouracil: potentially serious infection, patients with poor nutritional status

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease Control Rate (DCR): defined as the percentage of patients with a complete response, a partial response or a stable disease at 4 months after the start of treatment.

Secondary endpoints 7

1. Tolerability and safety will be assessed according to V5.0 of the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE). Adverse events will be recorded up to 30 days after the last dose of treatment. Treatment duration, administered doses, dose intensity, dose modifications, treatment delays and the reason for definitive treatment discontinuation will also be evaluated
2. Progression Free Survival (PFS) will be defined as the time between the start of treatment and the date of the first radiological progression (according to RECIST v1.1 criteria assessed by the investigator) or death (whatever the cause), whichever occurs first. Patients alive without progression will be censored at the date of the last available CT-scan.
3. Objective Response Rate (ORR) will be evaluated throughout the treatment, based on imaging and according to RECIST v1.1 criteria. The objective response rate is defined as the percentage of patients with a complete response or a partial response.
4. Duration Of Response (DOR) will be defined as the time between the first complete or partial response and the date of radiological progression or death, whichever comes first.
5. Overall Survival (OS) will be defined by the time between the start of treatment and the date of death (whatever the cause). Alive patients will be censored at the date of their last news.
6. Quality of life: will be assessed with the EORTC QLQ-C30 questionnaire. The questionnaire is completed before the treatment starts, and during the study every 2 months. Time to definitive deterioration of the global health score will also be made. It’s defined as the time from the start of treatment to the date of death or the date of more than 5 points decrease compared to baseline score. Patients alive without degradation will be censored at the date of last questionnaire available.
7. Time to WHO performance status (ps) degradation >2 will be collected at baseline and before each cure. Time to WHO ps degradation >2 is defined as the time from the start of treatment to the date of the first WHO ps >2 during the treatment period. Alive patients who are still under treatment with a WHO ps ≤ 2 will be censored at the date of the last available WHO ps value. Death will be considered as a WHO=5 so considered as an event.

Investigational products

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

Test 8

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Fondation Franc.Cancerologie Digestive

Sponsor organisation

Fondation Franc.Cancerologie Digestive

Address

7 Boulevard Jeanne D Arc

City

Dijon Cedex

Postcode

21001

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

Coordinator

Third parties 2

Locations

1 EU/EEA country · 45 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 14 files

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

Application history

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