Metastatic Lung Non-Small Cell CarcinomaPhase 1NCT04919369
All-Trans Retinoic Acid (ATRA) and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer
A Phase 1 study testing Atezolizumab and Tretinoin in people with Metastatic Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Small Cell Carcinoma, run by Dwight Owen at 1 site in United States.
Trial summary
This phase Ib trial is to find out the best dose and side effects of all-trans retinoic acid (ATRA) and atezolizumab in treating patients with non-small cell lung cancer that has come back (recurrent) or has spread to other places in the body (metastatic). Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8
- What is being tested?
- Atezolizumab and Tretinoin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 1 siteUnited States
- Study dates
- 18 Oct 2021to 3 Jul 2026
- Phase
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age >= 18 years
- Confirmed recurrent or metastatic non-small cell carcinoma of the lung of any histology for which there is no curative treatment option
- Measurable disease based on RECIST 1.1
- Patients must have received standard of care chemotherapy and/or immunotherapy. No limits to prior lines of therapy. Prior PD-1 and/or PD-L1 directed therapies are permitted
- Patients with adenocarcinoma and known actionable mutations with FDA-approved treatment options must have received all approved and standard of care treatment options (ie osimertinib for EGFR, alectinib for ALK, etc). Mutational testing is not required for patients with squamous cell non-small cell lung carcinoma
- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
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- Absolute neutrophil count (ANC) >= 1,500/mcL
- Lymphocytes ≥500/mcL
- Platelets >=100,000/mcL
- Serum creatinine =< 1.5 X upper limit of normal (ULN) OR measured or calculated creatinine clearance (glomerular filtration rate [GFR] can also be used in place of creatinine or creatinine clearance [CrCl]) >= 60 mL/min for subject with creatinine levels > 1.5 X institutional ULN
- Serum total bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubin levels > 1.5 ULN
- Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT]) and alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X ULN OR =< 5 X ULN for subjects with liver metastases
- Albumin >= 2.5 mg/dL
- International normalized ratio (INR) or prothrombin time (PT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or partial thromboplastin time (PTT) is within therapeutic range of intended use of anticoagulants
- Activated partial thromboplastin time (aPTT) =< 1.5 X ULN unless subject is receiving anticoagulant therapy as long as PT or PTT is within therapeutic range of intended use of anticoagulants
- Anticipated life expectancy of >= 3 months
- Willing to comply with study procedures
- Female subjects of childbearing potential must be willing to use an adequate method of contraception, for the course of the study through 120 days after the last dose of study medication
- Female subject of childbearing potential should have a negative urine or serum pregnancy within 72 hours prior to receiving the first dose of study medication. If the urine test is positive or cannot be confirmed as negative, a serum pregnancy test will be required
- Female subjects of childbearing potential should be willing to use 2 methods of birth control or be surgically sterile, or abstain from heterosexual activity for the course of the study through 5 months days after the last dose of study medication. Subjects should agree to ongoing pregnancy testing during the course of the study and after the end of study therapy. Female subjects of childbearing potential are those who have not been surgically sterilized or have not been free from menses for > 1 year
- Male subjects should agree to use an adequate method of contraception starting with the first dose of study therapy through 7 months after the last dose of study therapy. Males must refrain from donating sperm during study participation and for 7 months after the last dose of study medication
- Be willing and able to understand and sign the written informed consent document
- Ability to swallow and retain oral medication
- HIV-infected patients on effective anti-retroviral therapy with undetectable viral load within 6 months are eligible.
- History of hepatitis C virus (HCV) infection treated and cured.
Who cannot join
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has active autoimmune disease, including myasthenic syndrome, which has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
- Untreated central nervous system (CNS) metastases. Patients with treated brain metastases are eligible if they were clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization. The patient must have no evidence of grade >= 1 CNS hemorrhage based on pretreatment magnetic resonance imaging (MRI) or IV contrast computed tomography (CT) scan (performed within screening window)
- Pregnancy or breastfeeding
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- Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the trial, interfere with the subject's participation for the full duration of the trial, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
- Any patient who has experienced an unacceptable toxicity on prior checkpoint inhibitor therapy as detailed below:
- >= grade 3 adverse events (AE) related to checkpoint inhibitor
- Ongoing >= grade 2 immune-related AE associated with checkpoint inhibitor with the exception of endocrine toxicities as detailed below
- CNS, ocular or cardiac AE of any grade related to checkpoint inhibitor
- NOTE: Patients with a prior or ongoing endocrine AE are permitted to enroll if they are stably maintained on appropriate replacement therapy and are asymptomatic
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Comprehensive Cancer Center
Columbus, Ohio, 43210
About this study
Official title: A Phase Ib Dose De-Escalation Study of All-Trans Retinoic Acid (ATRA) and Atezolizumab in Patients With Advanced Non-Small Cell Lung Cancer
This phase Ib trial is to find out the best dose and side effects of all-trans retinoic acid (ATRA) and atezolizumab in treating patients with non-small cell lung cancer that has come back (recurrent) or has spread to other places in the body (metastatic). All-trans retinoic acid (ATRA) is made in the body from vitamin A and helps cells to grow and develop. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving all-trans retinoic acid (ATRA) and atezolizumab may help treat patients with non-small cell lung cancer.
Read the detailed description
PRIMARY OBJECTIVE:
- To determine the safety and tolerability of the combination of tretinoin (ATRA) and atezolizumab in patients with advanced non-small cell lung cancer (NSCLC) based upon the Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria.
SECONDARY OBJECTIVE:
- To determine the efficacy of the combination of ATRA and atezolizumab in patients with advanced NSCLC, including progression-free survival (PFS), objective response (ORR), disease control rate (DCR), and overall survival (OS) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
EXPLORATORY OBJECTIVE:
- To study the effect of ATRA on the levels of myeloid-derived suppressor cells (MDSCs) in peripheral blood of study patients.
OUTLINE:
Patients receive tretinoin orally (PO) on days 1-3 of cycles 1-3. Patients also receive atezolizumab intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks.
- Conditions
- Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
- Being tested
- Atezolizumab, Tretinoin
- Medical subject headings
- Carcinoma, Non-Small-Cell Lung, Lung Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AtezolizumabBiological
Also called MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A
Given IV
TretinoinDrug
Also called 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (tretinoin, atezolizumab) | Experimental | Patients receive tretinoin PO on days 1-3 of cycles 1-3. Patients also receive atezolizumab IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. Receives: Biological: Atezolizumab; Drug: Tretinoin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence of adverse events (AEs)
Safety will be measured by the occurrence of dose-limited toxicities (DLTs) as well as any other adverse events as defined in Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.
Measured: Up to 2 years
Secondary outcomes (4)
Overall response
Will be calculated and exact binomial 95% confidence interval will be provided.
Measured: Up to 2 years
Disease control rate
Will be calculated and exact binomial 95% confidence interval will be provided.
Measured: Up to 2 years
Overall survival (OS)
Kaplan-Meier methods will be used to estimate OS with 95% confidence interval (CI).
Measured: From initiation of therapy to death, or censored at last follow-up date if the subject is alive, assessed up to 2 years
Progression free survival (PFS)
Kaplan-Meier methods will be used to estimate PFS with 95% CI.
Measured: From initiation of therapy to the time of Response Evaluation Criteria in Solid Tumors (RECIST) progression or death, assessed up to 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Jun 2021
- Study start18 Oct 2021
- Primary completion20 Sep 2025
- Study completion3 Jul 2026
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Lung Non-Small Cell CarcinomaStudies of the same condition, open and under way.
- 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
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dwight Owen
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dwight Owen, Ohio State University Comprehensive Cancer Center
- Investigators
- Dwight H Owen, MD, MS, FACP, Principal investigator, Ohio State University Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04919369
- Sponsor's protocol ID
- OSU-20171
- Other IDs
- NCI-2021-03310
- Status last verified
- Jul 2026
- First submitted
- 3 Jun 2021
- Last updated
- 20 Jul 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase Ib Dose De-Escalation Study of All-Trans Retinoic Acid (ATRA) and Atezolizumab in Patients With Advanced Non-Small Cell Lung Cancer
- ClinicalTrials.gov ID
- NCT04919369
- Acronym / sponsor ID
- OSU-20171
- Conditions
- Metastatic Lung Non-Small Cell Carcinoma, Recurrent Lung Non-Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Dwight OwenUniversity, hospital or other
- Study start
- 18 Oct 2021 (actual)
- Primary completion
- 20 Sep 2025 (actual)
- Study completion
- 3 Jul 2026 (actual)
- First posted
- 9 Jun 2021 (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 phase Ib trial is to find out the best dose and side effects of all-trans retinoic acid (ATRA) and atezolizumab in treating patients with non-small cell lung cancer that has come back (recurrent) or has spread to other places in the body (metastatic). All-trans retinoic acid (ATRA) is made in the body from vitamin A and helps cells to grow and develop. Immunotherapy with monoclonal antibodies, such as atezolizumab, may help the body's immune system attack the cancer, and may interfere with the ability of tumor cells to grow and spread. Giving all-trans retinoic acid (ATRA) and atezolizumab may help treat patients with non-small cell lung cancer.
Detailed description
PRIMARY OBJECTIVE:
- To determine the safety and tolerability of the combination of tretinoin (ATRA) and atezolizumab in patients with advanced non-small cell lung cancer (NSCLC) based upon the Common Terminology Criteria for Adverse Events (CTCAE) version 5 criteria.
SECONDARY OBJECTIVE:
- To determine the efficacy of the combination of ATRA and atezolizumab in patients with advanced NSCLC, including progression-free survival (PFS), objective response (ORR), disease control rate (DCR), and overall survival (OS) based on modified Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1.
EXPLORATORY OBJECTIVE:
- To study the effect of ATRA on the levels of myeloid-derived suppressor cells (MDSCs) in peripheral blood of study patients.
OUTLINE:
Patients receive tretinoin orally (PO) on days 1-3 of cycles 1-3. Patients also receive atezolizumab intravenously (IV) on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed up every 12 weeks.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (tretinoin, atezolizumab) | Experimental | Biological: Atezolizumab, Drug: TretinoinPatients receive tretinoin PO on days 1-3 of cycles 1-3. Patients also receive atezolizumab IV on day 1. Cycles repeat every 21 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (25 listed)
- Age >= 18 years
- Confirmed recurrent or metastatic non-small cell carcinoma of the lung of any histology for which there is no curative treatment option
- Measurable disease based on RECIST 1.1
- Patients must have received standard of care chemotherapy and/or immunotherapy. No limits to prior lines of therapy. Prior PD-1 and/or PD-L1 directed therapies are permitted
- Patients with adenocarcinoma and known actionable mutations with FDA-approved treatment options must have received all approved and standard of care treatment options (ie osimertinib for EGFR, alectinib for ALK, etc). Mutational testing is not required for patients with squamous cell non-small cell lung carcinoma
Key exclusion criteria (12 listed)
- Is currently participating and receiving study therapy or has participated in a study of an investigational agent and received study therapy or used an investigational device within 4 weeks of the first dose of treatment
- Has active autoimmune disease, including myasthenic syndrome, which has required systemic treatment in the past 2 years (i.e. with use of disease modifying agents, corticosteroids or immunosuppressive drugs). Replacement therapy (eg, thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or pituitary insufficiency, etc.) is not considered a form of systemic treatment
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any other form of immunosuppressive therapy within 7 days prior to the first dose of trial treatment
- Cirrhosis (Child-Pugh B or worse) or cirrhosis with history of hepatic encephalopathy or clinically meaningful ascites resulting from cirrhosis. Clinically meaningful ascites is defined as ascites from cirrhosis requiring diuretics or paracentesis
- Untreated central nervous system (CNS) metastases. Patients with treated brain metastases are eligible if they were clinically stable with regard to neurologic function, off steroids after cranial irradiation (whole brain radiation therapy, focal radiation therapy, and stereotactic radiosurgery) ending at least 2 weeks prior to randomization, or after surgical resection performed at least 28 days prior to randomization. The patient must have no evidence of grade >= 1 CNS hemorrhage based on pretreatment magnetic resonance imaging (MRI) or IV contrast computed tomography (CT) scan (performed within screening window)
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 |
|---|---|---|
| AtezolizumabAlso: MPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280AGiven IV | Biological | Treatment (tretinoin, atezolizumab) |
| TretinoinAlso: 2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, AknotenGiven PO | Drug | Treatment (tretinoin, atezolizumab) |
Primary outcome
Incidence of adverse events (AEs)
Time frame: Up to 2 years
Safety will be measured by the occurrence of dose-limited toxicities (DLTs) as well as any other adverse events as defined in Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5. Frequency and severity of AEs and tolerability of the regimen will be collected and summarized by descriptive statistics. The maximum grade for each type of toxicity will be recorded for each patient, and frequency tables will be reviewed to determine toxicity patterns. All patients who have received at least one dose of the therapeutic agents will be evaluable for toxicity and tolerability.
4 secondary outcomes
Overall response
Time frame: Up to 2 years
Disease control rate
Time frame: Up to 2 years
Overall survival (OS)
Time frame: From initiation of therapy to death, or censored at last follow-up date if the subject is alive, assessed up to 2 years
Progression free survival (PFS)
Time frame: From initiation of therapy to the time of Response Evaluation Criteria in Solid Tumors (RECIST) progression or death, assessed up to 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Jul 2026.
- The JameslineLink provided by the sponsor.
- Individual participant dataSharing planned: No
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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.
Dwight H Owen, MD, MS, FACP principal investigator
Ohio State University Comprehensive Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Atezolizumab and Tretinoin in people with Metastatic Lung Non-Small Cell Carcinoma and Recurrent Lung Non-Small Cell Carcinoma, run by Dwight Owen at 1 site in United States.
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 25 inclusion and 12 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: finished, as of the sponsor's last update on 20 Jul 2026. 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 United States. 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?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Incidence of adverse events (AEs) (time frame: 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 20 Jul 2026.