Immunotherapy Combined With Radiation and Influenza Vaccine for Pancreatic Cancer.

NCT05116917 | Terminated Phase 2

• 1 other identifier: GI 2118
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

Brief Summary

Pancreatic cancer (PC) remains a dreadful disease due to its often advanced stage at diagnosis and poor sensitivity to chemotherapy. Progression after 1. line chemotherapy is inevitable in patients with advanced PC, and treatment options for patients who progress after 1. line chemotherapy are limited. Considering the emerging role of the tumor microenvironment, the combination of checkpoint blocking antibodies with immunomodulation of the tumor microenvironment could lead to better responses in tumor historically resistant to radiation and checkpoint blocking antibody approaches as single modalities. Influenza vaccination in cancer patients receiving immune checkpoint inhibitors resulted in a better survival, irrespective of the anticancer treatment outcome. Influenza vaccine facilitates both T- and B cell activation and drives interferon-gamma response, supporting the rationale for combining of influenza vaccine with immune checkpoint inhibition and radiation (NCT02866383). Based on these considerations, the proposed treatment with SBRT of 15 Gy in combination with nivolumab, ipilimumab and influenza vaccine may have the potential to provide meaningful clinical benefit by generating durable clinical responses, thereby improving quality of life (QoL) and potentially extending survival.

Conditions

Pancreatic Cancer

Keywords

Pancreatic cancer; Check point inhibitors; Influenza vaccine

Outcome Measures

Primary Outcomes (1)

• Objective response rate (ORR)

  ORR in all patients using Investigator assessments

  12 months

Secondary Outcomes (6)

• Duration of response (DoR)

  12 months

• Disease control rate (DCR)

  12 months

• Progression free survival (PFS)

  12 months

• Overall survival (OS)

  12 months

• EORTC QLQ-C30

  12 months

Study Arms (1)

Experimental Arm

EXPERIMENTAL

SBRT of 15 Gy will be given on day 1 of the first cycle. Nivolumab 3 mg/kg (up to 240 mg maximum) will be given on day 1 (± 3 days) of each 14-day treatment cycle until the progression of disease or maximum of 48 weeks, discontinuation due to toxicity, withdrawal of consent. Ipilimumab 1 mg/kg will be given on day 1 cycle 1 (± 3 days) and once more after 6 weeks. Nivolumab will be administered as an IV infusion over 60 (± 5) minutes and then, after a 30 minutes rest period, ipilimumab will be administered as an IV infusion over 30 (± 5) minutes. Seasonal influenza vaccine is given IM or via PharmaJet Stratis Needle-Free Injection System, 0.5 mL per dose as a single on day 1 cycle 1 (± 3 days).

Drug: Nivolumab; Drug: Ipilimumab; Biological: Influenza vaccine; Radiation: SBRT

Interventions

Nivolumab DRUG

3 mg/kg (up to 240 mg maximum) will be given on day 1 (± 3 days) of each 14-day treatment cycle

Also known as: Opdivo®

Experimental Arm

Ipilimumab DRUG

1 mg/kg will be given on day 1 cycle 1 (± 3 days) and once more after 6 weeks

Also known as: Yervoy®

Experimental Arm

Influenza vaccine BIOLOGICAL

Seasonal influenza vaccine is given IM or via PharmaJet Stratis Needle-Free Injection System, 0.5 mL per dose as a single on day 1 cycle 1 (± 3 days)

Experimental Arm

SBRT RADIATION

* A total dose of 15 Gy as a single fraction is prescribed as the mean dose to the PTV. * PTV should be covered by 95% isodose (PTV D99% \> 95%).

Experimental Arm

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent
• 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
• Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study
• Histological or cytological confirmation of advanced pancreatic carcinoma prior to entering this study
• Prior therapy requirements:
• There is no upper limit on the number of prior chemotherapy regimens received. Participants must have received and progressed during or after at least 1 line of systemic chemotherapy in the metastatic setting (gemcitabine or 5-FU based regimens).
• Notes:
• If a participant received adjuvant/neoadjuvant systemic combinational therapy, and progressed within 6 months, the adjuvant/neoadjuvant treatment will be considered as 1 line of systemic treatment.
• In general, discontinuation of 1 drug in a multi-drug regimen and continuation of other drug(s), is considered part of the same line of treatment. Restarting the same regimen after a drug holiday or maintenance chemotherapy can also be considered part of the same line of treatment. Switching from IV (5-FU) to an oral formulation (capecitabine) of the same drug is also considered part of the same line of treatment
• Minimum time from first systemic therapy for recurrent/metastatic adenocarcinoma of pancreas to progression should be at least 3 months
• Age 18 years and older
• ECOG/WHO Performance Status (PS) 0-1
• 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 not acceptable.
• Participants must have normal organ and marrow function as defined below:
• Absolute neutrophil count (ANC) ≥ 1.5 x 10⁹/L

You may not qualify if:

• 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
• 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
• Current or prior use of immunosuppressive medication within 14 days before the first dose of nivolumab, ipilimumab and radiation in combination with influenza vaccine. The following are exceptions to this criterion:
• Intranasal, inhaled, or topical steroids; or local steroid injections (e.g. intra-articular injection)
• Systemic corticosteroids at physiologic doses not to exceed 10 mg/day of prednisone or equivalent
• Steroids as premedication for hypersensitivity reactions (e.g. CT scan premedication)
• Participants should be excluded if they have known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• Allergies and Adverse Drug Reaction
• History of allergy to study drug components
• History of severe hypersensitivity reaction to any monoclonal antibody
• WOCBP who are pregnant or breastfeeding

Sponsors & Collaborators

• Herlev Hospital: lead

Study Sites (1)

Herlev and Gentofte Hospital

Herlev, 2730, Denmark

Location

MeSH Terms

Conditions

Pancreatic Neoplasms; Influenza, Human

Interventions

Nivolumab; Ipilimumab; Influenza Vaccines

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases; Respiratory Tract Infections; Infections; Orthomyxoviridae Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Viral Vaccines; Vaccines; Biological Products; Complex Mixtures

Study Officials

• Inna M Chen

  Herlev Sygehus

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: Subjects will be enrolled in the study to treatment with nivolumab, ipilimumab and radiation in combination with influenza vaccine, until 30 participants have been treated.

Study Record Dates

• First Submitted: October 23, 2021
• First Posted: November 11, 2021
• Study Start: November 5, 2021
• Primary Completion: October 19, 2023
• Study Completion: October 19, 2023
• Last Updated: May 28, 2024

Record last verified: 2024-05

Data Sharing

• IPD Sharing: Will not share

Locations

DK (1)