Randomized phase 3 trial comparing FOLFOX to gemcitabine in metastatic first-line in patients with pancreatic adenocarcinoma and non-fit for FOLFIRINOX (GEMFOX)

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Assistance Publique Hopitaux De Paris

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

8 Jul 2020 → ongoing

Decision date (initial)

2024-12-05

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-511904-18-00

EudraCT number

2019-001364-30

ClinicalTrials.gov

NCT04167007

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy

To assess the efficacy of FOLFOX in comparison to gemcitabine in metastatic first-line in patients with pancreatic adenocarcinoma and non-fit for FOLFIRINOX.

Secondary objectives 9

1. - The others efficacy parameters centered on the tumor: objective response rate and disease control rate (RECIST v1.1, in case of evaluable lesion), duration of response, duration of disease control
2. - The progression free survival (PFS)
3. - The evolution of biomarkers Ca 19-9 and CEA to assess their prognostic value at inclusion and their predictive value under treatment
4. - The toxicities according to International Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
5. - The safety of both arms
6. - The quality of life
7. - The dose intensity (DI) of each protocol
8. - The Quality-Adjusted Survival
9. - The rate and type of second-line / third-line regimens chemotherapy

Conditions and MedDRA coding

Pancreatic adenocarcinoma (PAC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 17

1. 1. Signed and dated informed consent, and willing and able to comply with protocol requirements,
2. 2. Histologically or cytologically proven adenocarcinoma of the pancreas,
3. 3. In absence of histologically or cytologically proven adenocarcinoma, a cluster of clinical, biological and radiological arguments consistent with the diagnosis: among these, a hypodense pancreatic tumor at CT and a Ca 19-9 greater than 500 UI/ml are essential prerequisites,
4. 4. Metastatic disease confirmed (stage IV),
5. 5. No prior therapy for metastatic disease (in case of previous adjuvant therapy, interval from end of chemotherapy and relapse must be >12 months),
6. 6. Age ≥18 years,
7. 7. Patient non-fit for FOLFIRINOX with ECOG performance status (PS) 0-2,
8. 8. For patients with ECOG performance status (PS) = 2, an albuminemia level >25 g/l is required,
9. 9. Haematological status: neutrophils (ANC) >2x109/L; platelets >100x109/L; haemoglobin ≥9g/dL,
10. 10. Adequate renal function: serum creatinine level <150μM and estimated creatinine clearance >30ml/min,
11. 11. Adequate liver function: AST (SGOT) and ALT (SGPT) ≤2.5xULN (≤5xULN in case of liver metastases),
12. 12. Total bilirubin ≤3 x ULN,
13. 13. QT / QTc interval at baseline ECG (performed within 1 month before randomization) < than 450 msec for men and < than 470 msec for women,
14. 14. Baseline evaluations performed before randomization: clinical and blood evaluations no more than 2 weeks (14 days) prior to randomization, tumor assessment (CT-scan or MRI, evaluation of non-measurable lesions) no more than 28days prior to randomization,
15. 15. Female patients must be surgically sterile, or be postmenopausal, or must commit to using reliable and appropriate methods of contraception during the study and during at least six months after the end of study treatment (when applicable). All female patients with reproductive potential must have a negative pregnancy test (β HCG) within 7 days prior to starting protocol treatment. Breastfeeding is not allowed.
16. 16. Male patients must agree to use effective contraception in addition to having their partner use a contraceptive method as well during the trial and during at least six months after the end of the study treatment
17. 17. Affiliation to a French social security system (recipient or assign).

Exclusion criteria 20

1. 1. History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
2. 2. Local or locally advanced disease (stage I to III),
3. 3. Patient uses warfarin or other antivitamin k,
4. 4. Patient receiving concomitant radiotherapy,
5. 5. Electrolytic report uncontrolled: hypercalcemia and/or hypokalemia and/or hypomagnesemia,
6. 6. Pre-existing permanent neuropathy (NCI grade ≥2),
7. 7. Poor nutritional status (albuminemia level ≤ 25 g/l)
8. 8. Known dihydropyrimidine dehydrogenase (DPD) total or partial deficiency (controlled before inclusion by DPD genotypage or uracilemia dosage whatever the anteriority),
9. 9.Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
10. 10. Treatment with any other investigational medicinal product within 28 days prior to study entry,
11. 11. Other serious and uncontrolled non-malignant disease (eg. active infection requiring systemic therapy, coronary stenting or myocardial infarction or stroke in the past 6 months),
12. 12. Known or historical active infection with HIV, or known active infection untreated with hepatitis B or hepatitis C,
13. 13. Known uncontrolled bacterial infection
14. 14. History or active interstitial lung disease (ILD),
15. 15. Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years, iv/ malignancy with indolent evolution not requiring treatment,
16. 16. Patients with known allergy to active substance or any excipient of study drugs,
17. 17. Allergy to iodinated contrast product
18. 18. Concomitant administration of live, attenuated virus vaccine and concomitant administration of prophylactic phenytoin.
19. 19. Patients under legal protection or unable to consent
20. 20- Participation in another interventional research (medical treatment or medical device).

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Overall survival (OS) at 24 months

Secondary endpoints 9

1. - Objective response rate and disease control rate (RECIST criteria 1.1), duration of response, duration of disease control.
2. - Progression-free survival (PFS) will be defined as the delay between the date of inclusion and the date of the first event (progression or death) or date of last news if the patient is alive without any progression.
3. - Ca 19-9 and CEA levels, at inclusion and their dynamic change under treatment.
4. - Toxicities will be described by type of toxicities and grades according to International Common Terminology Criteria for Adverse Events (CTCAE) version 5.0.
5. - Safety: rate of serious adverse events, grade 3-4 toxicities (hematologic and non-hematologic). Adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) version 5.0.
6. - Quality of life will be studied by means of the EORTC QLQ C-30 questionnaire, the health-related quality of life (HRQoL) and the consensual geriatric minimum data set (SOFOG) for patients ≥75 years and
7. - The dose-intensity (DI) of each protocol will be calculated based on the number of cycles received by each patient. The relative DI will be calculated as the ratio of the DI to the DI indicated in the protocol (obtained as the dose specified per cycle in mg/m²).
8. - The Quality-adjusted Time WIthout Symptoms of disease or Toxicity (Q-TWIST)
9. - Type of second-line and third-line regimens and the date of beginning of first-cycle of each line will be collected.

Investigational products

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

Test 3

Comparator 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Assistance Publique Hopitaux De Paris

Sponsor organisation

Assistance Publique Hopitaux De Paris

Address

Porte 23, 1 Avenue Claude Vellefaux 1 Avenue Claude Vellefaux

City

Paris Cedex 10

Postcode

75475

Country

France

Scientific contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Jean-Baptiste BACHET

Public contact point

Organisation

Assistance Publique Hopitaux De Paris

Contact name

Pr Jean-Baptiste BACHET

Locations

1 EU/EEA country · 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 11 files

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

Application history

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