Ipilimumab, Nivolumab, Tocilizumab and Radiation in Pretreated Patients With Advanced Pancreatic Cancer (TRIPPLE-R)
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|ClinicalTrials.gov Identifier: NCT04258150|
Recruitment Status : Active, not recruiting
First Posted : February 6, 2020
Last Update Posted : February 15, 2021
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 (TME), the combination of checkpoint blocking antibodies with agents that target the inhibitory effects of the TME could lead to better responses in tumor historically resistant to checkpoint blocking antibody approaches. Inflammation is one of the hallmarks of cancer, and contributes to PC initiation, enhanced invasiveness and metastasis. The immune-modulating cytokine interleukin-6 (IL-6) facilitates the inflammation cascade and key pathways within the respective TME, among others promotion of tumor-induced immunosuppression and facilitation of metastasis. Thus, IL-6 inhibition approach can potentially directly affect the immunosuppressive TME compartment.
To explore the synergy of the proposed combinatorial approach, participants with locally advanced/metastatic pancreatic tumors who have progressed during or after at least 1 line of systemic chemotherapy in the metastatic setting will receive nivolumab and ipilimumab administered in combination with radiotherapy and tocilizumab. It is anticipated that this clinical study will inform the use of this 3-drug combination for further phase II and/or phase III clinical testing.
|Condition or disease||Intervention/treatment||Phase|
|Pancreatic Cancer||Drug: Nivolumab Drug: Ipilimumab Drug: Tocilizumab Radiation: SBRT||Phase 2|
This is a phase II study assessing ipilimumab, nivolumab and tocilizumab in combination with SBRT of 15 Gy in patients with locally advanced or metastatic PC whose disease has progressed on at least 1. line chemotherapy with either a 5-FU-containing and /or gemcitabine containing chemotherapy. The trial is designed as an investigator initiated prospective open-label study in patients with advanced PC to determine the efficacy and safety ipilimumab, nivolumab and tocilizumab in combination with SBRT.
This study will consist of Part A, Lead-in, as well as a possible Part B, non-randomized expansion (Part B: Expansion) or a possible Part B, randomized controlled study (Part B: RCT).
Initially, patients will be enrolled in the study to treatment with ipilimumab, nivolumab and tocilizumab in combination with SBRT, until 30 patients have been treated (Part A: Lead-in). Patient recruitment and tumor assessment will be monitored on an ongoing basis. This Part A: Lead-in involves Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.
Multicenter extension will be activated in case of successfully completed lead-in phase and the format of that Part B will be determined based on the responses seen in the first 30 patients in Part A. A protocol amendment will be made if criteria are met to proceed to Part B. The protocol amendment will include available data from Part A and any changes to study design, additional sites and statistical plan, if needed.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||30 participants|
|Intervention Model:||Single Group Assignment|
|Intervention Model Description:||Initially, patients will be enrolled in the study to treatment with ipilimumab, nivolumab and tocilizumab in combination with SBRT, until 30 patients have been treated (Part A: Lead-in). This Part A: Lead-in involves Department of Oncology, Herlev and Gentofte Hospital, Copenhagen University Hospital, Denmark.|
|Masking:||None (Open Label)|
|Official Title:||TRIPPLE-R: Phase 2 Study in Pretreated Patients With Advanced Pancreatic Cancer to Assess Efficacy of Ipilimumab, Nivolumab and Tocilizumab in Combination With Radiation|
|Actual Study Start Date :||April 16, 2020|
|Estimated Primary Completion Date :||March 1, 2022|
|Estimated Study Completion Date :||March 1, 2023|
SBRT of 15 Gy will be given on day 1 of the first cycle. Nivolumab 6 mg/kg (up to 480 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 (± 3 days) twice in total every 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. Tocilizumab 8 mg/kg is given IV on day 1 (± 3 days) over 1-hour, repeated every 4 weeks. Tocilizumab infusion over 30 minutes is allowed after 5. infusion in the absence of infusion related events.
6 mg/kg IV q4w
Other Name: Opdivo®
1 mg/kg IV twice q6w
Other Name: Yervoy®
8 mg/kg IV q4w
- Objective response rate (ORR) [ Time Frame: 12 months ]ORR in all patients using Investigator assessments according to RECIST 1.1
- Duration of response (DoR) [ Time Frame: 12 months ]DoR in all patients using Investigator assessments according to RECIST 1.1.
- Disease control rate (DCR) [ Time Frame: 12 months ]DCR in all patients using Investigator assessments according to RECIST 1.1.
- Progression free survival (PFS) [ Time Frame: 12 months ]PFS in all patients using Investigator assessments according to RECIST 1.1.
- Overall survival (OS) [ Time Frame: 12 months ]OS in all patients using Investigator assessments according to RECIST 1.1.
- EORTC QLQ-C30 [ Time Frame: 12 months ]Adjusted mean change from baseline in global QoL score from the EORTC QLQ-C30 questionnaire.
- Incidence of treatment-related AEs, SAEs, AEs leading to discontinuation, death, and laboratory abnormalities [ Time Frame: 12 months ]AEs, physical examinations, laboratory findings (including clinical chemistry, hematology), vital signs (including blood pressure and pulse).
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04258150
|Herlev & Gentofte University Hospital, Denmark|
|Herlev, Denmark, 2730|
|Principal Investigator:||Inna M Chen, MD||Herlev Hospital|