Safety and potential efficacy of combining immunotherapy with chemotherapy and radiation for treatment of borderline resectable, nonresectable locally advanced or metastatic pancreatic cancer

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Region Hovedstaden

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Neoplasms [C04]

Trial duration

2 Jun 2020 → ongoing

Decision date (initial)

2024-10-08

Transition trial

Yes

Low-intervention

No

Rare-disease indication

No

Vulnerable population

Yes

Funding sources

Danish Cancer Society

External identifiers

EU CT number

2024-518173-34-00

EudraCT number

2019-003759-13

ClinicalTrials.gov

NCT04247165

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Therapy, Efficacy, Safety

To evaluate the safety and toxicity profile of nivolumab with ipilimumab in combination with standard chemotherapy and followed by nivolumab in combination with gemcitabine and nab-paclitaxel and magnetic resonance imaging (MRI) and/or computed tomography (CT)-guided adaptive SBRT for the treatment of BRPC, LAPC or mPC.

Secondary objectives 4

1. To evaluate the PFS and PFS rate (PFSR) of nivolumab with ipilimumab in combination with standard chemotherapy and followed by nivolumab in combination with gemcitabine and nab-paclitaxel and MRI and/or CT-guided adaptive SBRT for the treatment of BRPC, LAPC or mPC.
2. To evaluate the OS and OS rate (OSR) of nivolumab with ipilimumab in combination with standard chemotherapy and followed by nivolumab in combination with gemcitabine and nab-paclitaxel and MRI and/or CT-guided adaptive SBRT for the treatment of BRPC, LAPC or mPC.
3. To evaluate the anti-tumor activity (objective response rate and duration of response) of nivolumab with ipilimumab in combination with standard chemotherapy and followed by nivolumab in combination with gemcitabine and nab-paclitaxel and MRI and/or CT-guided adaptive SBRT for the treatment of BRPC, LAPC or mPC.
4. To determine the rate of downstaging to surgical resection of nivolumab with ipilimumab in combination with standard chemotherapy and followed by nivolumab in combination with gemcitabine and nab-paclitaxel and MRI and/or CT-guided adaptive SBRT for the treatment of BRPC and LAPC.

Conditions and MedDRA coding

Borderline resectable, locally advanced or metastatic pancreatic cancer (BRPC, LAPC or mPC)

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. Signed informed consent o Subjects must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care o Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
2. Histological or cytological confirmation of BRPC, LAPC or mPC prior to entering this study
3. No prior chemotherapy regimens received for PC
4. Age 18 years or older
5. Life expectancy greater than 6 months
6. ECOG/WHO Performance Status (PS) 0-1
7. All participants will be required to undergo mandatory pre- and on-treatment biopsies at acceptable clinical risk as judged by the investigator. An archival pre-treatment sample is acceptable
8. Patients must have normal organ and marrow function as defined below: o Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L o Platelet count ≥ 100 x 10⁹/L o Serum bilirubin ≤ 1.5 x upper limit of normal (ULN) (patients with Gilbert's Syndrome must have a total bilirubin ≤ 50 mmol/L) o Aspartate transaminase (AST)/Alanine transaminase (ALT) ≤ 5 x ULN o Serum creatinine ≤ 1.5 x ULN or creatinine clearance (CrCl) ≥ 40 mL/min (using the Cockcroft-Gault formula)
9. Women of childbearing potential (WOCBP) must use method(s) of contraception as indicated in Appendix 3. For a teratogenic study drug and/or when there is insufficient information to assess teratogenicity (preclinical studies have not beendone), a highly effective method(s) of contraception (failure rate of less than 1% per year) is required. The individual methods of contraception and duration should be determined in consultation with the investigator. WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 30 days plus the time required for the investigational drug to undergo five half-lives. The half-life of nivolumab and ipilimumab is up to 25 days and 18 days, respectively. WOCBP should therefore use an adequate method to avoid pregnancy for 23 weeks (30 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug
10. Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year. The investigator shall review contraception methods and the time period that contraception must be followed. Men that are sexually active with WOCBP must follow instructions for birth control when the half-life of the investigational drug is greater than 24 hours, contraception should be continued for a period of 90 days plus the time required for the investigational drug to undergo five half-lives. Men who are sexually active with WOCBP must continue contraception for 31 weeks (90 days plus the time required for nivolumab to undergo five half-lives) after the last dose of investigational drug. Women who are not of childbearing potential (ie, who are postmenopausal or surgically sterile) as well as azoospermic men do not require contraception
11. Subjects must have signed and dated a BIOPAC approved written informed consent form in accordance with regulatory and institutional guidelines

Exclusion criteria 7

1. Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CD137, or anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell co-stimulation or checkpoint pathways
2. Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results
3. Participants with active, known or suspected autoimmune disease. Participants with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll.
4. Participants with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications. Inhaled or topical steroids and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease.
5. Patients should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
6. Allergies and Adverse Drug Reaction o History of allergy to study drug components o History of severe hypersensitivity reaction to any monoclonal antibody
7. WOCBP who are pregnant or breastfeeding

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 1

1. Incidence of treatment-related AEs, SAEs, AEs leading to discontinuation, death, and laboratory abnormalities

Secondary endpoints 4

1. Median PFS using RECIST v1.1 and PFSR at 6, 9, and 12 months
2. Median OS and OSR at 6 months, 1 year, and 2 years
3. Objective Response Rate (ORR) and median duration of response (DOR) by RECIST v1.1
4. Rate of downstaging to surgical resection

Investigational products

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

Test 5

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Region Hovedstaden

Sponsor organisation

Region Hovedstaden

Address

Borgmester Ib Juuls Vej 1

City

Herlev

Postcode

2730

Country

Denmark

Scientific contact point

Organisation

Region Hovedstaden

Contact name

Sponsor Investigator Inna Chen

Public contact point

Organisation

Region Hovedstaden

Contact name

Sponsor Investigator Inna Chen

Third parties 1

Locations

1 EU/EEA country · 1 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 7 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