FFCD 1605- OPTIPRIME: A phase II study evaluating FOLFOX + panitumumab according to a ‘stop-and-go’ strategy with a reintroduction loop after progression on fluoropyrimidine as maintenance treatment, as the first line in patients with metastatic colorectal adenocarcinoma without a RAS mutation

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

26 Apr 2018 → 19 May 2025

Decision date (initial)

2024-11-13

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-518740-20-00

EudraCT number

2017-001587-38

ClinicalTrials.gov

NCT03584711

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

Evaluate the disease control duration

Secondary objectives 9

1. Progression-free survival 1 (first radiological progression or death)
2. Successive periods of progression-free survival
3. The best tumour response during treatment, the early response rate at 8 weeks and the maximum depth of response, evaluated according to the RECIST V1.1 criteria according to the investigator and centralised imaging reviews
4. Overall survival
5. Quality of life of patients (EORTC QLQ-C30)
6. Time to definitive deterioration of the overall health score
7. Safety profile, particularly in regard to skin toxicity events (acneiform rash, xerosis, paronychia)
8. The predictive value of early evolution (at two weeks) of the circulating tumour DNA level correlated with the RECIST 1.1 response rate and the PFS 1
9. The appearance of resistance mutations and clonal selection through analysis of circulating tumour DNA every two months

Conditions and MedDRA coding

metastatic colorectal adenocarcinoma

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 13

1. Histologically proven colorectal adenocarcinoma without RAS mutation
2. Confirmed, non-resectable metastatic disease (Stage IV)
3. No prior chemotherapy except perioperative or adjuvant chemotherapy discontinued for more than 12 months
4. At least one measurable metastasis according to the RECIST v1.1 criteria
5. Age ≥ 18 years
6. WHO ≤ 2
7. Neutrophils > 1,500 /mm3, platelets > 100,000/mm3, Hb > 9 g/dL
8. Creatinine clearance > 50 mL/min according to the Cockcroft & Gault formula, 24h proteinuria < 1 g
9. Serum bilirubin < 25 µmol/L, AST, ALT, Alk Phos < 2.5 x ULN or < 5 x ULN in case of liver metastases
10. PT > 60%, albumin ≥ 25 g/L
11. Life expectancy ≥ 3 months
12. Patient affiliated to a social security scheme
13. Patient informed and informed consent form signed

Exclusion criteria 22

1. Presence of brain metastases unless controlled
2. RAS mutation (KRAS or NRAS mutation) or BRAF mutation
3. Patient taking warfarin. If treated with an anticoagulant at the indicated effective dose, this must be replaced with low molecular weight heparin before inclusion
4. Partial or complete DihydroPyrimidine Dehydrogenase (DPD) deficiency (defined as uracilemia ≥16 ng/ml)
5. Peripheral neuropathy > 1 (NCI CTCAE v4.0)
6. Patient with interstitial pneumonitis or pulmonary fibrosis
7. History of chronic diarrhoea or inflammatory disease of the colon or rectum, or obstruction or sub-obstruction during symptomatic treatment
8. Chronic skin disease poorly controlled
9. Treatment with sorivudine or its chemically related analogues such as brivudine
10. Any known specific contraindication or allergy to the medicinal products used in the study (see SmPC Annex 7)
11. Association with the yellow fever vaccine
12. Patient simultaneously included in another clinical trial involving an investigational drug
13. High blood pressure not controlled by medical treatment (PAS > 160 mmHg and/or PAD >90 mmHg)
14. Any progressive disease not stabilised over the past 6 months: hepatic failure, renal failure, respiratory failure
15. The following conditions in the 6 months prior to inclusion: myocardial infarction, severe/unstable angina, coronary artery bypass surgery, congestive heart failure NYHA class II, III or IV, stroke or transient ischaemic attack
16. Patient who has received a transplant, is seropositive for HIV, hepatitis B or hepatitis C or has other immunodeficiency syndromes
17. History of malignant diseases during the past 5 years except basal cell carcinoma of the skin or cervical carcinoma in situ, properly treated
18. QT/QTc interval > 450 msec for men and > 470 msec for women
19. K+ < LLN, Mg2+ < LLN, Ca2+ < LLN
20. Lack of effective contraception in patients (men and/or women) of childbearing age, pregnant or breastfeeding women, women of childbearing age who have not had a pregnancy test. Women of childbearing potential should agree to use a method of contraception during treatment of the trial and at least 4 months after discontinuation of oxaliplatin therapy, at least 2 months after discontinuation of panitumumab therapy and at least 30 days after discontinuation of 5-fluorouracil or capecitabine. Men must agree to use a method of contraception during treatment and at least 6 months after stopping oxaliplatin therapy and at least 3 months after stopping 5-fluorouracil or capecitabine.
21. Persons in custody or under wardship
22. Impossibility of undergoing medical monitoring during the trial for geographical, social or psychological reasons

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Disease control duration.

Secondary endpoints 12

1. Progression-free survival 1 (PFS1 or PFS)
2. Progression-free survival 2 (PFS 2)
3. Successive progression-free survivals (PFS3), 4 (PFS4), etc
4. The best tumour response
5. The early response rate at 6 weeks
6. The depth of response
7. Overall survival
8. Quality of life (EORTC QLQ C-30)
9. The dose intensity
10. The adverse events
11. The predictive value of early evolution
12. The predictive value of the appearance of resistance mutation(s)

Investigational products

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

Test 5

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

Locations

2 EU/EEA countries · 2 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

Summary of results Art. 37(4) CTR

Layperson summary Annex V

Documents 19 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