PRODIGE 49 - OSCAR: Systemic oxaliplatin or in intra-arterial chemotherapy combined with LV5FU2 ± Irinotecan, and targeted therapy, in first-line treatment of metastatic colorectal cancer restricted to the liver

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] - Neoplasms [C04]

Trial duration

8 Nov 2024 → ongoing

Decision date (initial)

2024-11-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

External identifiers

EU CT number

2024-518553-41-00

EudraCT number

2016-002393-12

ClinicalTrials.gov

NCT02885753

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Efficacy

Comparison of radiological and/or clinical progression free survival between intra-arterial administration of oxaliplatin (arms A and C) and intravenous administration of oxaliplatin (arms B and D). Progression was assessed according to the criteria RECIST v1.1 and according to the investigator.

Secondary objectives 13

1. Toxicities according to NCI-CTC v4.0
2. Evaluation of the best response under treatment, and radiological progression-free survival after central review of the X-rays
3. Best response obtained under treatment according to the investigator
4. Overall survival (median)
5. Hepatic progression free survival (median)
6. Evaluation of quality of life (QLQ-C30)
7. Early tumor shrinkage (response > 20%) at 8 weeks
8. Depth of response
9. Secondary resection rate
10. Histological response in case of secondary resection
11. Evolution of tumoral marker (CEA)
12. Progression free survival under 'active' treatment
13. Subgroup analysis on patients being treated with intra-arterial oxaliplatin versus intravenous oxaliplatin with bichemotherapy and with trichemotherapy

Conditions and MedDRA coding

colon cancer and rectal with liver metastasis

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically proven colorectal adenocarcinoma with hepatic metastasis(es)
2. At least one measurable hepatic metastasis according to the criteria RECIST v1.1
3. No other metastatic sites except lung nodules accepted if number ≤ 3 and < 10 mm
4. RAS mutation status known (determination of KRAS mutation [exons 2,3 and 4]and NRAS [exons 2,3 and 4])
5. Age ≥ 18
6. OMS ≤ 2
7. No prior chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months and the 1st course of FOLFOX or mFOLFIRINOX IV without targeted therapy before randomisation (protocolar treatment)
8. Life expectancy > 3 months
9. PNN > 1500 /mm3, platelets > 100 000/mm3, Hb > 9 g/dL
10. Total bilirubin < 25 μmol/L, AST < 5x UNL, ALT < 5 x UNL, x UNL, ALP < 5 x UNL, PT > 60%, proteinuria from 24H < 1 g
11. Creatinine clearance > 50 mL/min according to MDRD formula
12. Patient affiliated to a social security scheme
13. Patient information and signature of the informed consent

Exclusion criteria 22

1. Contraindications specific to the installation of a KTHIA: thrombosis of the hepatic artery, arterial vascular anatomy may compromise a secondary hepatic resection.
2. Patient immediately eligible for a curative therapy (surgical and/or percutaneous) after discussion in CPR
3. Following alterations in the 6 months prior to inclusion: myocardial infarction, angina, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischemic attack
4. Hypertension not controlled by medical treatment (SBP> 140 mmHg and/or DBP> 90 mmHg with blood pressure taken according to the diagram of the HAS)
5. A history of abdominal fistula, gastrointestinal perforation, intraabdominal abscess or active gastrointestinal bleeding in the 6 months preceding the start of treatment
6. Progressive gastroduodenal ulcer, wound or fractured bone
7. Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in the 4 weeks before starting the treatment
8. Abdominal or major extra-abdominal surgery (except diagnostic biopsy) or irradiation in the 4 weeks before starting the treatment - Transplant patients, HIV positive or other immune deficiency syndromes
9. Transplant patients, HIV positive or other immune deficiency syndromes
10. Any progressive pathology not balanced over the past 6 months: hepatic failure, renal failure, respiratory failure
11. Peripheral neuropathy > 1 (NCI CT v4.0)
12. Patient with interstitial pneumonitis or pulmonary fibrosis
13. History of chronic diarrhea or inflammatory disease of the intestine, colon or rectum, or unresolved occlusion or sub-occlusion in symptomatic treatment
14. History of malignant pathologies during the past 5 years except basocellular skin carcinoma or in situ cervical carcinoma, properly treated
15. Patient already included in another clinical trial with an experimental molecule
16. Any known specific contraindication or allergy to the treatments used in the study (cf RCP Appendix 7)
17. Partial or complete DPD deficiency (Uracilemia ≥ 16 ng/ml)
18. QT/QTc range > 450 msec for men and > 470 msec for women
19. K+ < LNL, Mg2+ < LNL, Ca2+ < LNL
20. Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age not having had a pregnancy test
21. Persons deprived of liberty or under supervision
22. Information du patient et signature du consentement éclairé

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Comparison of radiological and/or clinical progression free survival between intra-arterial administration of oxaliplatin (arms A and C) and intravenous administration of oxaliplatin (arms B and D). Progression was assessed according to the criteria RECIST v1.1 and according to the investigator.

Secondary endpoints 11

1. The adverse events will be graded according to NCI CTCAE v4.0 before each chemotherapy cycle.
2. The best response under treatment will be evaluated based on the response RECIST v1.1 according to the investigator to the different Xrays; it will be described by the levels in the different categories: complete or partial response, stability, progression or non-evaluable.
3. Overall survival: defined by the time between the date of treatment beginning and the date of death, whatever the cause; patients alive will be censured at the date of latest news.
4. Hepatic progression free survival: defined by the time between the date of treatment beginning and the date of first hepatic progression or death, whatever the cause; patients alive without progression will be censured at the date of latest news.
5. Early tumour shrinkage (difference > 20%) at 8 weeks: defined as the relative difference between the sum of the largest diameters of the RECIST target lesions at 8 weeks and this sum at inclusion (prior to C1 before randomization).
6. Depth of response: defined as the relative difference between the sum of the largest diameters of the RECIST target lesions in the NADIR (in the absence of new lesions or progression of non-target lesions) and the sum of the largest diameters of the RECIST target lesions at inclusion.
7. Secondary resection rate: Rate of patients who were able to benefit from a resection of their tumor (primary and/or secondary) after treatment (by mentioning the character R0, R1 or R2)
8. Evaluation of the histological response, TRG (Rubbia-Brandt L et al. Annals Oncol 2007) in case of hepatic resection
9. Evolution of the marker during treatment
10. Quality of life
11. Progression free survival under 'active' treatment defined by the time between the date of treatment beginning and the date of first progression under treatment (excluding therapeutic break) or death, whatever the cause; patients alive without progression will be censured at the date of latest news.

Investigational products

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

Test 2

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

Postcode

21000

Country

France

Scientific contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

julien taieb

Public contact point

Organisation

Fondation Franc.Cancerologie Digestive

Contact name

gaba lila

Locations

2 EU/EEA countries · 48 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 12 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