Metastatic pancreatic cancer MedDRA version: 21.0 Level: LLT Classification code 10033604 Term: Pancreatic cancer System Organ Class: 100000004864 MedDRA version: 21.1 Level: LLT Classification code 10033605 Term: Pancreatic cancer metastatic System Organ Class: 100000004864
Conditions
Interventions
Trade Name: OPDIVO
Product Name: Nivolumab
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: Nivolumab
Other descriptive name: Nivolumab
Concentration unit: mg/ml milligr
Sponsors
Department of Oncology, Herlev & Gentofte Hospital
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • 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 10?/L - Platelet count = 75 x 10?/L - Serum bilirubin = 1.5 x upper limit of normal (ULN) - AST/ALT = 5 x ULN - Serum creatinine = 1.5 x ULN or CrCl = 40 mL/min (using the Cockcroft-Gault formula) • 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 been done), 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 • 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 con
Exclusion criteria
Exclusion criteria: • 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 combined 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, infusion related) • 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 • Already received the influenza vaccine for the current season of inclusion • WOCBP who are pregnant or breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To assess the efficacy of nivolumab, ipilimumab and radiation in combination with influenza vaccine in terms of objective response rate (ORR).;Secondary Objective: - To further assess the efficacy of nivolumab, ipilimumab and radiation in combination with influenza vaccine in terms of duration of response (DoR), disease control rate (DCR), progression free survival (PFS), PFS at 2 months (PFS2), PFS at 4 months (PFS4), PFS at 6 months (PFS6), overall survival (OS), OS at 6 months (OS6), and OS at 12 months (OS12). - To assess the health-related quality of life (QoL) as measured by EORTC QLQ-C30 global QoL scale. - To assess the safety and tolerability profile of nivolumab, ipilimumab and radiation in combination with the influenza vaccine. Exploratory To explore the association between anti-tumor activity and specific biomarker measures in the tumor tissue, stool samples, saliva samples and in peripheral blood prior to treatment and following administration of nivolumab, ipilimumab and radiation in combination with influenza vaccine. ;Primary end point(s): ORR using Investigator assessments according to RECIST 1.1.;Timepoint(s) of evaluation of this end point: tumor response are assessed by CT-scan every 8 week during treatment for the individual participants Overall the endpoint is assessed once 15 and 30 participants have completed at least 2 post-baseline assessment. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): DoR, DCR, PFS, PFS2, PFS4 and PFS6 in all participants using Investigator assessments according to RECIST 1.1. OS, OS6, and OS12. Adjusted mean change from baseline in global QoL score from the EORTC QLQ-C30 questionnaire. Adverse events (AEs), physical examinations, laboratory findings (including clinical chemistry, hematology), vital signs (including blood pressure and pulse). ;Timepoint(s) of evaluation of this end point: Overall secondary enpoints are analysed at the end of study | — |
Countries
Denmark
Contacts
Public ContactPrincipal Investigator Inna Chen
Department of Oncology, Herlev & Gentofte Hospital
Outcome results
None listed