Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

All Conditions

Rare Diseases

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Endocrine System Diseases

Pancreatic Cancer

Antineoplastic Agents

All Drugs and Chemicals

Nivolumab

Ipilimumab

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

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.

Tocilizumab

* 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%).

SBRT

Inna M Chen, MD

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.

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.

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.

Ipilimumab, Nivolumab, Tocilizumab and Radiation in Pretreated Patients With Advanced Pancreatic Cancer

TRIPPLE-R: Phase 2 Study in Pretreated Patients With Advanced Pancreatic Cancer to Assess Efficacy of Ipilimumab, Nivolumab and Tocilizumab in Combination With Radiation

ORR in all patients using Investigator assessments according to RECIST 1.1

DoR in all patients using Investigator assessments according to RECIST 1.1.

DCR in all patients using Investigator assessments according to RECIST 1.1.

PFS in all patients using Investigator assessments according to RECIST 1.1.

OS in all patients using Investigator assessments according to RECIST 1.1.

Adjusted mean change from baseline in global QoL score from the EORTC QLQ-C30 questionnaire.

AEs, physical examinations, laboratory findings (including clinical chemistry, hematology), vital signs (including blood pressure and pulse).

Spots Global Cancer Trial Database for roactemra

Every month we try and update this database with for roactemra cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for roactemra

Every month we try and update this database with for roactemra cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for roactemra cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.