Neoplasms

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Gastrointestinal Neoplasms

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Gastrointestinal Diseases

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Pancreatic Cancer

Antineoplastic Agents

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Anti-Infective Agents

Nivolumab

Tretinoin

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Immune Checkpoint Inhibitors

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Antineoplastic Agents, Immunological

Keratolytic Agents

Nivolumab: 3mg/kg intravenously on day 1.

All-trans retinoic acid (Vesanoid) 45 mg/m2 on days 1-14. The dose of Vesanoid can be increased with addition of 15 mg/m2 in next course of treatment if there is no severe adverse effects. Therefore, the dose of Vesanoid could be 60 mg/m2 from the second course, 75 mg/m2 from the third course, till the maximal dose of 150 mg/m2 if patients tolerated the treatment. The decision of dose escalation is left to in-charge physician.

The treatment cycle will repeat every 2 weeks.

Nivolumab, an immune checkpoint inhibitors targeting PD-1, represents a popular treatment option for patients with cancers via immunological mechanism. However, previous studies using nivolumab alone in pancreatic cancer have failed.

Our previous basic studies revealed that all-trans retinoic acid repressed pancreatic adenocarcinoma cell growth and colony formation. All-trans retinoic acid represses ADAR1, a member of interferon-stimulated genes and a negative regulator of IFNs signaling. On the other hand, all-trans retinoic acid simultaneously increases PD-L1 expression for cancer cells to evade immune surveillance. Since combination of anti-PD1 antibody and all-trans retinoic acid may block self-regulating negative feedback loops of IFNs response, this therapeutic strategy may improve outcomes of pancreatic adenocarcinoma patients.

all trans retinoic acid

Li-Yuan Bai

This study is to examine the anticancer activity of the combination therapy with all-trans retinoic acid and nivolumab in patients with chemotherapy-refractory advanced or metastatic pancreatic adenocarcinoma.

Pancreatic cancer is an aggressive and lethal disease. Even two combination regimens, FOLFIRINOX and albumin-bound paclitaxel in combination with gemcitabine, are superior to gemcitabine alone as the first-line treatments, the prognosis of patients with locally advanced or metastatic pancreatic cancer remains poor, with a median overall survival of 8 to 11 months and an estimated 2-year survival of only 2%. Even more, there is currently no available treatment proven beneficial for patients who fail the second-line therapy with liposomal irinotecan in combination with 5-FU.

Immune checkpoint inhibitors targeting PD-1 or PD-L1 represent a popular treatment option for patients with some kinds of cancers, but previous studies in pancreatic cancer have failed. One critical challenge for immunotherapy in pancreatic cancer is to find efficient therapeutic approaches to reverse this "cold" tumor into a "hot" tumor. Our previous basic studies revealed that all-trans retinoic acid repressed pancreatic adenocarcinoma cell growth and colony formation. Set-to-set genetic analysis revealed that genes regulated by all-trans retinoic acid were predominantly involved in immune response including interleukin-6, tumor necrotic factor-α, IFNs signaling, and PD-L1. Furthermore, mice bearing pancreatic cancer treated with combination of anti-PD-1 and all-trans retinoic acid had a significantly longer survival compared to mice treated with anti-PD-1 or all-trans retinoic acid alone.

Based on the previous findings, we propose this pilot, compassionate use of combination therapy with all-trans retinoic acid and nivolumab for patients with locally advanced or metastatic pancreatic adenocarcinoma who are refractory to current available treatment. This study will also examine ADAR1 as a novel prognostic and predictive biomarker for pancreatic adenocarcinoma patients. This study will help to delineate the role of ADAR1 as a predictive biomarker for immunotherapy, all-trans retinoic acid as a suppressor of ADAR1, and most importantly, the combination of all-trans retinoic acid and nivolumab as an effective anticancer therapy for patients with pancreatic adenocarcinoma.

Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer

Treatment With Nivolumab and All-trans Retinoic Acid for Patients With Refractory Pancreatic Cancer

The median duration of time from the time of registration until death

Overall response is evaluated using Response Evaluation Criteria in Solid Tumors criteria (RECIST 1.1). A participant is considered to have responded if either of the following outcomes is achieved:

1. Complete Response: Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm
2. Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.

The median duration of time from the time of registration until disease progression or death. Disease progression is assessed using RECIST 1.1 criteria.

Spots Global Cancer Trial Database for adar1

Every month we try and update this database with for adar1 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 adar1

Every month we try and update this database with for adar1 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 adar1 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.