Sequential Treatment With GEMBRAX and Then FOLFIRINOX Followed by MRI-guided Radiotherapy in Patients With Locally Advanced Pancreatic Cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Institut Regional Du Cancer De Montpellier

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04], Diseases [C] - Digestive System Diseases [C06]

Trial duration

17 Jun 2021 → ongoing

Decision date (initial)

2024-08-12

Transition trial

Yes

Low-intervention

Yes

Rare-disease indication

No

Vulnerable population

No

External identifiers

EU CT number

2024-515344-23-00

EudraCT number

2020-002517-18

ClinicalTrials.gov

NCT04570943

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

1: Evaluating the efficacy of the Gembrax/Folfirinox chemotherapy sequence
2: To assess the tolerability of MRI-guided adaptive stereotactic radiotherapy in non-progressive patients after SEQ 1.

Secondary objectives 16

1. Assessing the tolerability of the chemotherapy sequence
2. Evaluate the acute toxicity of radiotherapy
3. Evaluate dosimetric results
4. Correlate dosimetric results with tolerance and survival
5. Evaluate progression-free survival of radiotherapy
6. Evaluate overall survival of radiotherapy
7. Assess local disease control of radiotherapy
8. Evaluating progression-free survival in the overall study
9. Evaluate overall study survival
10. Evaluate tolerability of overall treatment
11. Evaluate late toxicity of overall study
12. Evaluate resection rate and quality
13. Evaluate histological response to treatment
14. Evaluate evolution of CA 19.9 marker
15. Evaluate Quality of Life
16. Establish a biological database to search for biological predictive factors based on circulating tumor DNA (ctDNA) and immune cells, as well as to characterize the immune consequences of treatment based on immune cells.

Conditions and MedDRA coding

local advenced pancreatic adenocarcinoma

Study design 1 period

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 7

1. Patient between 18 and 75 years of age on the date of signing the consent form
2. Histologically or cytologically proven pancreatic adenocarcinoma.
3. Eastern Cooperative Oncology Group (ECOG) Performance status ≤ 1
4. Non-resectability criteria, according to NCCN 1.2015 recommendations (Appendix 14) validated during centralized review.
5. Non-metastatic patient confirmed by TAP scan and liver MRI
6. Feasibility of MRI-guided radiotherapy confirmed by centralized review
7. CA 19.9 < 500 IU/mL (without icteric cholestasis). If CA 19.9 between 500 IU/mL and 1000 IU/mL, patient may be included if PET scan and peritoneal MRI (peritoneal MRI optional) show no distant metastasis. If CA 19.9 >1000 IU/ML, the patient cannot be included.

Exclusion criteria 9

1. Any previous treatment for pancreatic cancer (chemotherapy, radiotherapy, surgery, targeted therapy or experimental therapy, etc.).
2. Other concomitant cancer or history of cancer, with the exception of treated cervical cancer in situ, basal or squamous cell skin carcinoma, superficial bladder tumor (Ta, Tis, and T1) or curatively treated tumor of good prognosis without chemotherapy and without evidence of disease within 3 years prior to inclusion.
3. History of radiotherapy leading to a foreseeable overlap with the radiotherapy treatment under study (history of abdominal irradiation)
4. Peripheral neuropathy ≥ grade 2
5. ECG with QTc interval greater than 450 ms for men and greater than 470 ms for women
6. Intolerance or allergy to one of the study drugs (gemcitabine, Nab-paclitaxel, oxaliplatin, irinotecan, 5-FU) or to an excipient of one of the drugs (e.g. fructose) described in the Contraindications or Warnings and Special Precautions sections of the SPCs or Prescribing Information.
7. Pregnant or breast-feeding woman. If a patient is of childbearing age, she must have a negative pregnancy test (serum β-hCG) documented 72 hours prior to inclusion.
8. Brivudine-based treatment within 4 weeks before or after 5-fluorouracil treatment (potentially fatal interaction).
9. Patient having received a live attenuated vaccine within 10 days prior to inclusion and up to 6 months following cessation of chemotherapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. 1: Non-progression rate at 4 months (SEQ1 success rate) according to RECIST 1.1 criteria 2: Rate of RT-related acute digestive non-toxicity within 90d of grade ≥3 assessed by NCI CTC AE v5.0 classification

Secondary endpoints 17

1. Tolerance of chemotherapy sequence assessed by NCI CTC AE v5.0 classification
2. Tolerance (acute and delayed toxicities) of radiotherapy sequence assessed by NCI CTC AE v5.0 classification
3. Collection of dosimetric results obtained in terms of dose/volume on predictive dosimetry (PTV coverage by prescription dose on totalized dosimetry, dose received at GTV....)
4. Collection and summation of dosimetric results obtained in terms of dose/volume for adaptive radiotherapy sessions, and comparison with predictive dosimetry.
5. Correlation of dose to organs at risk (duodenum, small intestine, stomach, colon) with the occurrence of digestive toxicities (predictive and adaptive dosimetry)
6. Correlation of PTV coverage and GTV dose with progression-free survival and overall survival (predictive and adaptive dosimetry)
7. Progression-free survival defined as time from radiotherapy start date to date of 1st documented progression or date of death from any cause. - Overall survival defined as time from radiotherapy start date to date of death from any cause.
8. Overall survival defined as time from radiotherapy start date to date of death from any cause.
9. Local disease control rate defined as the proportion of patients without local progression, with time to local progression defined as the time from radiotherapy start date to the date of documented local progression. Patients without local progression will be censored at the date of last news
10. Progression-free survival defined as time from inclusion to date of 1st documented progression or date of death from any cause.
11. Overall survival defined as time from date of inclusion to date of death from any cause.
12. Tolerance of overall treatment assessed by NCI CTC AE v5.0 classification.
13. Resection rate defined as the percentage of patients operated on up to 6 months post-radiotherapy.
14. R0 resection rate
15. Histological response rate* according to CAP score30, 31, 32
16. Assess the prognostic impact of CA 19.9 evolution on survival
17. Evolution of Quality of Life scores assessed by the EORTC QLQ-C30 and PAN 26 questionnaires.

Investigational products

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

Test 7

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Institut Regional Du Cancer De Montpellier

Sponsor organisation

Institut Regional Du Cancer De Montpellier

Address

208 Avenue Des Apothicaires

City

Montpellier Cedex 5

Postcode

34298

Country

France

Scientific contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

Dr Fabienne PORTALES

Public contact point

Organisation

Institut Regional Du Cancer De Montpellier

Contact name

catherine fiess

Locations

1 EU/EEA country · 13 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 18 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