What is the mechanism of action of this treatment?

All-trans retinoic acid (ATRA) promotes cell growth and development, helping to differentiate cancer cells into more normal cells, potentially reducing their malignancy. Atezolizumab, a monoclonal antibody, targets PD-L1, a protein that tumors use to evade the immune system. By blocking PD-L1, Atezolizumab enhances the body's immune response against cancer cells. This combination aims to normalize cancer cell behavior and boost the immune system's ability to fight the cancer, which is crucial for improving patient outcomes.

What side effects are associated with this type of intervention?

All-trans retinoic acid (ATRA) can cause side effects such as hypertriglyceridemia, dry skin, and mucous membrane irritation. Atezolizumab, an immunotherapy drug, is associated with fatigue, decreased appetite, nausea, and immune-related adverse events like pneumonitis, colitis, and hepatitis. Combining these treatments may result in a combination of these side effects, necessitating careful monitoring.

What prior FDA approvals exist?

Atezolizumab, a monoclonal antibody that enhances the immune response against cancer cells, has been approved by the FDA for the treatment of metastatic non-small cell lung cancer (NSCLC) that has progressed during or following platinum-containing chemotherapy. In the phase III OAK trial, atezolizumab demonstrated improved overall survival compared to docetaxel in patients with advanced NSCLC. Other similar immunotherapies include nivolumab and pembrolizumab, which have also shown efficacy in treating advanced NSCLC by targeting PD-1/PD-L1 pathways to boost the immune system's ability to fight cancer.

What other types of research exist?

Promising novel alternatives for lung cancer treatment include Pembrolizumab, an immune checkpoint inhibitor that has shown improved survival rates in various trials, and Durvalumab, another PD-L1 inhibitor that has demonstrated efficacy in combination with chemotherapy. Additionally, Ramucirumab combined with Pembrolizumab has shown improved overall survival in patients with progressive disease after initial immunotherapy.

← Back to Search

Monoclonal Antibodies

ATRA + Atezolizumab for Lung Cancer

Phase 1

Recruiting

Led By Dwight H Owen, MD

Research Sponsored by Dwight Owen

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Age >= 18 years

Eastern Cooperative Oncology Group (ECOG) performance status of 0-2

Must not have

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

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

Timeline

Screening 3 weeks

Treatment Varies

Follow Up up to 2 years

Awards & highlights

No Placebo-Only Group

Summary

This trial tests ATRA and atezolizumab in patients with advanced non-small cell lung cancer. ATRA helps cells grow normally, and atezolizumab boosts the immune system to fight cancer.

Who is the study for?

This trial is for adults with recurrent or metastatic non-small cell lung cancer who have tried standard treatments. They must be able to take oral medication, not have curable cancer options left, and agree to use birth control. People with certain health conditions, active autoimmune diseases, or untreated brain metastases can't join.

What is being tested?

The trial tests the combination of ATRA (a vitamin A derivative) and atezolizumab (an immunotherapy drug) to find the best dose and monitor side effects in patients whose lung cancer has returned or spread.

What are the potential side effects?

Possible side effects include immune system reactions that may affect organs, infusion-related reactions from atezolizumab, fatigue, digestive issues like nausea or diarrhea from ATRA, as well as potential blood abnormalities.

Eligibility Criteria

Inclusion Criteria

You may be eligible if you check “Yes” for the criteria below

Select...

I am 18 years old or older.

Select...

I am able to care for myself and perform daily activities.

Select...

I can swallow and keep down pills.

Select...

My lung cancer has returned or spread and cannot be cured.

Select...

I had hepatitis C but have been treated and cured.

Exclusion Criteria

You may be eligible for the trial if you check “No” for criteria below:

Select...

I have severe liver disease with complications like confusion or fluid in my abdomen.

Select...

I have an autoimmune disease treated with strong medication in the last 2 years.

Select...

I have an immune system disorder or have been on steroids or other immune-weakening medicines in the last week.

Select...

I had severe side effects from previous immunotherapy.

Select...

I have had side effects in my brain, eyes, or heart from immunotherapy.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ up to 2 years

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~up to 2 years

This trial's timeline: 3 weeks for screening, Varies for treatment, and up to 2 years for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Incidence of adverse events (AEs)

Secondary study objectives

Disease control rate

Overall response

Overall survival (OS)

+1 more

Other study objectives

Effect of ATRA on the levels of myeloid-derived suppressor cells (MDSCs)

Side effects data

From 2009 Phase 4 trial • 163 Patients • NCT00835198

10%

Cold

Headache

100%

80%

60%

40%

20%

Study treatment Arm

Tretinoin Gel 0.025%

Dapsone Gel 5% and Tretinoin Gel 0.025%

Awards & Highlights

No Placebo-Only Group

All patients enrolled in this study will receive some form of active treatment.

Trial Design

1Treatment groups

Experimental Treatment

Group I: Treatment (tretinoin, atezolizumab)Experimental Treatment2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Atezolizumab

2016

Completed Phase 3

~5860

Tretinoin

2013

Completed Phase 4

~2040

0 / 10Eligibility criteria met

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

All-trans retinoic acid (ATRA) promotes cell growth and development, helping to differentiate cancer cells into more normal cells, potentially reducing their malignancy. Atezolizumab, a monoclonal antibody, targets PD-L1, a protein that tumors use to evade the immune system. By blocking PD-L1, Atezolizumab enhances the body's immune response against cancer cells. This combination aims to normalize cancer cell behavior and boost the immune system's ability to fight the cancer, which is crucial for improving patient outcomes.

Integrated microbiome, metabolome, and proteome analysis identifies a novel interplay among commensal bacteria, metabolites and candidate targets in non-small cell lung cancer.