PREOPANC-5

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Amsterdam UMC

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Analytical, Diagnostic and Therapeutic Techniques and Equipment [E] - Therapeutics [E02], Diseases [C] - Neoplasms [C04]

Trial duration

19 Sep 2024 → ongoing

Decision date (initial)

2024-04-29

Transition trial

No

Low-intervention

No

Rare-disease indication

Yes

Vulnerable population

No

External identifiers

EU CT number

2023-508707-20-00

ClinicalTrials.gov

NCT06384560

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Safety, Efficacy

PREOPANC-5 investigates whether neoadjuvant triple treatment with mFOLFIRINOX, pembrolizumab and stereotactic ablative radiotherapy (SABR), followed by resection and adjuvant mFOLFIRINOX and pembrolizumab improves progression free survival in patients with (borderline) resectable pancreatic cancer

Secondary objectives 8

1. Overall survival
2. Resection rates
3. Safety and Toxcitiy
4. Quality of life (QoL)
5. Therapy completion rates
6. Radiological response
7. Biochemical responses
8. Pathologic responses

Conditions and MedDRA coding

Borderline resectable pancreatic cancer (BRPC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Histologically or cytologically confirmed pancreatic cancer (WHO VI or VII)
2. Male or female participants who are at least 18 years of age on the day of signing informed consent
3. (Borderline) resectable tumor (according to DPCG criteria, see protocol table 1)
4. ECOG performance status 0 or 1; Ability to undergo surgery, radiotherapy, chemotherapy and immunotherapy
5. Leucocytes (WBC) ≥ 3.0 X 109/l; Platelets ≥ 100X 109 /l
6. Hemoglobin ≥ 6 mmol/l
7. Renal function: E-GFR > 50 ml/min
8. Bilirubin < 50 µmol/l or planned for biliary drainage
9. A male participant must agree to use a contraception as detailed in Appendix 5 of this protocol during the treatment period and for at least 18 weeks after the last dose of study treatment and refrain from donating sperm during this period
10. A female participant is eligible to participate if she is not pregnant (see Appendix 5), not breastfeeding, and at least one of the following conditions applies: Nota woman of childbearing potential (WOCBP) as defined in Appendix 5 OR A WOCBP who agrees to follow the contraceptive guidance in Appendix 5 during the treatment period and for at least 18 weeks after the last dose of study treatment
11. Written informed consent

Exclusion criteria 21

1. Metastatic or locally advanced (i.e. unresectable) pancreatic cancer
2. Has a known history of Hepatitis B (defined as Hepatitis B surface antigen [HBsAg] reactive) or known active Hepatitis C virus infection.
3. Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the participant’s participation for the full duration of the study, or is not in the best interest of the participant to participate, in the opinion of the treating investigator.
4. Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial.
5. Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 120 days after the last dose of trial treatment.
6. Has had an allogenic tissue/solid organ transplant.
7. Has contra-indications for MRI (only for Amsterdam UMC and UMCU): Pacemakers or implanted defibrillators, deep brain stimulators, cochlear implants; Patients who have a metallic foreign body in their eye, or who have an aneurysm clip in their brain, cannot have an MRI scan since the magnetic field may dislodge the metal; Patients with severe claustrophobia not able to tolerate an MRI scan.
8. Serious concomitant systemic disorders that would compromise the safety of the patient or his/her ability to complete the study, at the discretion of the investigator
9. Complete dihydropyrimidine dehydrogenase deficiency
10. A woman of childbearing potential (WOCBP) who has a positive urine pregnancy test within 72 hours prior to start of treatment / (see Appendix 5). If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
11. Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study intervention.
12. Has received prior therapy with an anti-PD-1, anti-PD-L1, or antiPDL2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (eg, CTLA-4, OX40, CD137)
13. Has received prior systemic anti-cancer therapy including investigational agents for pancreatic cancer
14. Has received prior radiotherapy within 2 weeks of start of study intervention
15. Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette–Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (eg, FluMist®) are live attenuated vaccines and are not allowed. COVID vaccines are allowed.
16. Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 7 days prior to the first dose of study drug.
17. Has a known additional malignancy that is progressing or has required active treatment within the past 2 years. Participants with basal cell carcinoma of the skin, squamous cell carcinoma of the skin or carcinoma in situ (eg, breast carcinoma, cervical cancer in situ) that have undergone potentially curative therapy are not excluded.
18. Has severe hypersensitivity (≥Grade 3) to pembrolizumab and/or any of its excipients.
19. Has active autoimmune disease that has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment and is allowed.
20. Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis.
21. Has an active infection requiring systemic therapy.

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Progression free survival, defined as the time from inclusion to the clinical trial to disease recurrence/progression or death from any cause

Secondary endpoints 18

1. Overall survival
2. Resection rate
3. pR0 resection rate
4. Postoperative complications
5. Toxicity
6. Quality of life (QoL)
7. Completion of neoadjuvant chemotherapy
8. Completion of neoadjuvant immunotherapy
9. Radiological response rate
10. Serum CA 19-9 response
11. Serum CEA response
12. Pathologic response
13. Immune responses
14. sR0 resection rate
15. Completion of adjuvant chemotherapy
16. Completion of neoadjuvant SABR
17. Completion of adjuvant immunotherapy
18. lymph node tumor-negative resection rate

Investigational products

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

Test 1

Auxiliary 4

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Amsterdam UMC

Sponsor organisation

Amsterdam UMC

Address

De Boelelaan 1117

City

Amsterdam

Postcode

1081 HV

Country

Netherlands

Scientific contact point

Organisation

Amsterdam UMC

Contact name

Prof. J.Wilmink

Public contact point

Organisation

Amsterdam UMC

Contact name

Prof. J.Wilmink

Sponsor responsibilities

Article 77 compliance

Amsterdam UMC

Contact point sponsor

Amsterdam UMC

Article 77 implementation

Amsterdam UMC

Locations

1 EU/EEA country · 6 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 6 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