Nivolumab, Ipilimumab and Chemoradiation in Treating Patients With Locally Advanced Pancreatic Cancer. (LAPTOP)
|The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT04247165|
Recruitment Status : Recruiting
First Posted : January 29, 2020
Last Update Posted : June 18, 2020
Pancreatic ductal adenocarcinoma (PDAC) remains a dreadful disease due to its often advanced stage at diagnosis and poor sensitivity to chemotherapy. A locally unresectable tumor (locally advanced pancreatic cancer (LAPC)) is present in 30% of the cases and is defined as a surgically unresectable tumor encasing the adjacent arteries [celiac axis, superior mesenteric artery (SMA)]. In these patients, chemotherapy has been the standard treatment for decades, optionally combined with radiotherapy. The results of small randomized trials comparing chemoradiotherapy with chemotherapy of patients with LAPC are divergent. 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. Furthermore, the addition of standard-of-care chemotherapy could further potentiate the anti-tumor effects of immunotherapy approaches by reducing the tumor burden, exposing antigens, and directly affecting the immunosuppressive TME compartment.
To explore the safety and synergy of the proposed combinatorial approach, participants with locally advanced PC will receive nivolumab and ipilimumab administered in combination with gemcitabine and nab-paclitaxel followed by immune-chemoradiation.
|Condition or disease||Intervention/treatment||Phase|
|Locally Advanced Pancreatic Cancer (LAPC)||Drug: Gemcitabine Drug: Nab-paclitaxel Drug: Nivolumab Drug: Ipilimumab Radiation: SBRT||Phase 1 Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||20 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||LAPTOP: Phase 1/2 Study in Locally Advanced Pancreatic Cancer to Assess Safety and Potential Efficacy of Dual Checkpoint Inhibition in Combination With Gemcitabine and Nab-paclitaxel Followed by Immune-chemoradiation.|
|Actual Study Start Date :||June 2, 2020|
|Estimated Primary Completion Date :||February 2023|
|Estimated Study Completion Date :||February 2024|
Nivolumab 3 mg/kg will be given on day 1 (± 2 days) of each 28-day treatment cycle until the progression of disease, discontinuation due to toxicity, withdrawal of consent. Ipilimumab 1 mg/kg will be given once only on day 1 cycle 1. Nivolumab will be administered as an IV infusion over 30 (± 5) minutes and then, after a 30 minutes rest period, ipilimumab will be administered as an IV infusion over 30 (± 5) minutes. Pre-medication for chemotherapy (based on standard-of-care and local institutional standards) and chemotherapy will then be administered after a further 30 minutes rest period.
The recommended dose of nab-paclitaxel is 100 mg/m2 administered as an IV infusion over 30 to 40 minutes on Days 1, 8, and 15 of each 28-day cycle. Gemcitabine 800 mg/m2 will be administered over 30 to 40 minutes immediately after nab-paclitaxel on Days 1, 8, and 15 of each 28-day cycle.
800 mg/m2 Day 1, 8, 15: Q4W IV Infusion
100 mg/m2 Day 1, 8, 15: Q4W IV Infusion
Other Name: Abraxane®
3 mg/kg Day 1, Q4W IV Infusion
Other Name: Opdivo®
1 mg/kg Day 1 Cycle 1 IV Infusion
Other Name: Yervoy®
Patients will be planned and treated with SBRT on a MRidian MR guided Linac.
Prescription dose shall be according to the following specifications:
- Incidence of treatment-related AEs, SAEs, AEs leading to discontinuation, death, and laboratory abnormalities [ Time Frame: 12 months ]
- Median PFS using RECIST v1.1 [ Time Frame: 12 months ]
- Median OS [ Time Frame: 24 months ]
- Objective Response Rate (ORR) by RECIST v1.1 [ Time Frame: 12 months ]
- Rate of downstaging to surgical resection [ Time Frame: 12 months ]
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): NCT04247165
|Contact: Inna M Chen, MD||+45 firstname.lastname@example.org|
|Principal Investigator:||Inna M Chen, MD||Herlev and Gentofte Hospital|