Effect of DrugEarly Phase 1NCT05482451
Nivolumab and All-trans Retinoic Acid for Pancreatic Cancer
A Early Phase 1 study testing Nivolumab and all trans retinoic acid in people with Effect of Drug, run by China Medical University Hospital at 1 site in Taiwan.
Trial 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. Read more about this study
- Who is it for?
- Ages 20 to 100 years
- Conditions the study is for
- Effect of Drug
- What is being tested?
- Nivolumab and all trans retinoic acid
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 10 participants
- Where
- 1 siteTaiwan
- Study dates
- 1 Mar 2021to 28 Feb 2025
- Phase
- Early Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 20 to 100 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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)
Who cannot join
- 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:
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Treatment With Nivolumab and All-trans Retinoic Acid for Patients With Refractory Pancreatic Cancer
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.
Read the detailed description
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.
- Conditions
- Effect of Drug
- Being tested
- Nivolumab, all trans retinoic acid
- Keywords
- Pancreatic cancer, Nivolumab, All-trans retinoic acid, Vesanoid, ADAR1
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NivolumabDrug
Also called Opdivo
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.
all trans retinoic acidDrug
Also called Vesanoid
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Drug: Nivolumab; Drug: all trans retinoic acid |
What is being measured
The primary outcome is the main question the study is designed to answer.
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:
- 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
- Partial Response: At least a 30% decrease in the sum of diameters of target lesions, taking as reference the baseline sum diameters.
Measured: From the date of registration until the end of treatment, up to 2 years.
Secondary outcomes (1)
Progression-free survival
The median duration of time from the time of registration until disease progression or death. Disease progression is assessed using RECIST 1.1 criteria.
Measured: From the date of registration until disease progression or death, up to 3 years.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Aug 2022
- Study start1 Mar 2021
- Primary completion28 Feb 2025 (estimated)
- Study completion28 Feb 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Effect of DrugStudies of the same condition, open and under way.
- More trials run by China Medical University HospitalThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Early Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 10 participants (actual)
Sponsor and investigators
- Lead sponsor
- China Medical University Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Li-Yuan Bai, Principal investigator, China Medical University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05482451
- Sponsor's protocol ID
- CMUH110-REC1-013
- Status last verified
- Aug 2024
- First submitted
- 27 Jul 2022
- Last updated
- 21 Aug 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Age, basic informations
Study at a glance
From the registry record, last updated by the sponsor on 21 Aug 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Treatment With Nivolumab and All-trans Retinoic Acid for Patients With Refractory Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT05482451
- Acronym / sponsor ID
- CMUH110-REC1-013
- Conditions
- Effect of Drug
- Keywords
- Pancreatic cancer, Nivolumab, All-trans retinoic acid, Vesanoid, ADAR1
- Phase
- Early Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 10 participants (actual)
- Lead sponsor
- China Medical University HospitalUniversity, hospital or other
- Study start
- 1 Mar 2021 (actual)
- Primary completion
- 28 Feb 2025 (estimated)
- Study completion
- 28 Feb 2025 (estimated)
- First posted
- 1 Aug 2022 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nivolumab + all-trans retinoic acid | Experimental | Drug: Nivolumab, Drug: all trans retinoic acidNivolumab: 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. |
Who may qualify
- Ages
- 20 to 100 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- 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
Key exclusion criteria (11 listed)
- 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:
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| NivolumabAlso: OpdivoNivolumab, 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. | Drug | Nivolumab + all-trans retinoic acid |
| all trans retinoic acidAlso: VesanoidOur 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. | Drug | Nivolumab + all-trans retinoic acid |
Primary outcome
Overall response
Time frame: From the date of registration until the end of treatment, up to 2 years.
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.
1 secondary outcome
Progression-free survival
Time frame: From the date of registration until disease progression or death, up to 3 years.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Aug 2024.
- Individual participant dataSharing planned: No. Age, basic informations
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Li-Yuan Bai principal investigator
China Medical University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Early Phase 1 study testing Nivolumab and all trans retinoic acid in people with Effect of Drug, run by China Medical University Hospital at 1 site in Taiwan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 15 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 21 Aug 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Taiwan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Early Phase 1 (sometimes called Phase 0) studies give a very small amount of a treatment to a few people, mainly to see how the body handles it.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Overall response (time frame: From the date of registration until the end of treatment, up to 2 years.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Aug 2024.