Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer

NCT05482451 | Active Not Recruiting Early Phase 1

• 1 other identifier: CMUH110-REC1-013
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Effect of Drug

Keywords

Pancreatic cancer; Nivolumab; All-trans retinoic acid; Vesanoid; ADAR1

Outcome Measures

Primary Outcomes (1)

• Overall response

  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.

  From the date of registration until the end of treatment, up to 2 years.

Secondary Outcomes (1)

• Progression-free survival

  From the date of registration until disease progression or death, up to 3 years.

Other Outcomes (1)

• Overall survival

  From the date of registration to the date of patients death, up to 3 years.

Study Arms (1)

Nivolumab + all-trans retinoic acid

EXPERIMENTAL

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.

Drug: Nivolumab; Drug: all trans retinoic acid

Interventions

Nivolumab DRUG

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.

Also known as: Opdivo

Nivolumab + all-trans retinoic acid

all trans retinoic acid DRUG

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.

Also known as: Vesanoid

Nivolumab + all-trans retinoic acid

Eligibility Criteria

• Age: 20 Years - 100 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients will be included in the study if they meet all of the following criteria:
• Patients with age ≥ 20 years old
• Histologically confirmed pancreatic adenocarcinoma
• Unresectable locally advanced, recurrent or metastatic diseases ineligible or unsuitable for further surgical or radiation interventions
• Documented disease progression within 6 months after standard chemotherapies or no available standard chemotherapy. The standard chemotherapies include gemcitabine, nab-paclitaxel, S-1, and FOLFIRINOX. Patient who has prior anti-PD1/anti-PD-L1 treatment will not be eligible.
• ECOG Performance Status 0-2
• Documented measurable disease as defined by RECIST v1.1
• Adequate hematologic parameters, and hepatic and renal functions defined as
• absolute neutrophil count ≥ 1,000/μL
• platelets ≥ 75,000/μL
• total bilirubin ≤ 2.5X ULN (≤ 5X ULN if attributable to liver metastases)
• AST/ALT ≤ 2.5X ULN (≤ 5X ULN if attributable to liver metastases)
• serum creatinine ≤ 2 mg/dL or creatinine clearance ≥ 30 mL/min (by calculated or 24-hour urine collection)
• Normal ECG or ECG without any clinical significant findings
• Able to understand and sign an informed consent (or have a legal representative who is able to do so)

You may not qualify if:

• Patients will be excluded from the study if they meet any of the following criteria:
• History of allergic reaction to all-trans retinoic acid or nivolumab
• Patient with liver cirrhosis with Child-Pugh score ≥ 8 (Late Child-Pugh B and Child-Pugh C)
• Active CNS metastasis defined by clinical symptoms, cerebral edema, steroid or anti-convulsant requirement, or progressive growth. Patients with a history of CNS metastasis or cord compression are allowed in the study if they have been treated and are clinically stable
• With clinically significant gastrointestinal disorder including bleeding, inflammation, occlusion or diarrhea \> grade 1
• With uncontrolled intercurrent illness that could limit study compliance or judged to be ineligible for the study by the investigators including, but not limited to, any of the following:
• ongoing or active infection requiring antibiotic treatment
• symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
• psychiatric illness or social situation that would preclude study compliance
• Pregnant or breast feeding women (a urine pregnancy test must be performed on all patients who are of childbearing potential before entering the study, and the result must be negative)
• Patients taking the following medications: immunosuppressants, corticosteroids with the exception of administration topically (e.g., external, intra-articular, intranasal, ophthalmic, or inhalational use) or temporarily (e.g., for treatment or prophylaxis of contrast medium allergy or adverse events), antitumor therapies (e.g., chemotherapies, molecular-targeted therapies, immunotherapies), radiopharmaceuticals with the exception of diagnostic purposes, transplant therapies, vitamin A, antifibrinolytic agents (tranexamic acid, aminocaproic acid, aprotinin), inducers (rifampicin, glucocorticoids, phenobarbital and pentobarbital) or inhibitors (ketoconazole, cimetidine, erythromycin, verapamil, diltiazem and cyclosporine) of the hepatic P450 system, and other unapproved drugs (e.g., investigational use of drugs, unapproved combined formulations, unapproved dosage forms).

Sponsors & Collaborators

• China Medical University Hospital: lead

Study Sites (1)

China Medical University Hospital

Taichung, Please Select, 404, Taiwan

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Nivolumab; Tretinoin

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Vitamin A; Retinoids; Carotenoids; Polyenes; Alkenes; Hydrocarbons, Acyclic; Hydrocarbons; Organic Chemicals; Cyclohexenes; Cyclohexanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Terpenes; Diterpenes; Pigments, Biological; Biological Factors

Study Officials

• Li-Yuan Bai

  China Medical University Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 27, 2022
• First Posted: August 1, 2022
• Study Start: March 1, 2021
• Primary Completion: February 28, 2025
• Study Completion: February 28, 2025
• Last Updated: August 21, 2024

Record last verified: 2024-08

Data Sharing

• IPD Sharing: Will not share

Locations

TW (1)