Clinical Trials /

All-Trans Retinoic Acid (ATRA) and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer

NCT04919369

Description:

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.

Related Conditions:
  • Non-Small Cell Lung Carcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: All-Trans Retinoic Acid (ATRA) and Atezolizumab for the Treatment of Recurrent or Metastatic Non-Small Cell Lung Cancer
  • 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

Clinical Trial IDs

  • ORG STUDY ID: OSU-20171
  • SECONDARY ID: NCI-2021-03310
  • NCT ID: NCT04919369

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

Interventions

DrugSynonymsArms
AtezolizumabMPDL 3280A, MPDL 328OA, MPDL-3280A, MPDL3280A, MPDL328OA, RG7446, RO5541267, TecentriqTreatment (tretinoin, atezolizumab)
Tretinoin2,4,6,8-Nonatetraenoic acid, 3, 7-dimethyl-9-(2,6,6-trimethyl-1-cyclohexen-1-yl)-, (all-E)-, Aberel, Airol, Aknoten, all trans-Retinoic acid, All-trans Retinoic Acid, All-trans Vitamin A Acid, all-trans-Retinoic acid, all-trans-Vitamin A acid, ATRA, Avita, beta-Retinoic Acid, Cordes Vas, Dermairol, Epi-Aberel, Eudyna, Renova, Retin-A, Retin-A MICRO, Retin-A-Micro, Retinoic Acid, Retisol-A, Ro 5488, Stieva-A, Stieva-A Forte, Trans Retinoic Acid, Trans Vitamin A Acid, trans-Retinoic Acid, Tretinoinum, Vesanoid, Vitamin A Acid, Vitamin A acid, all-trans-, VitinoinTreatment (tretinoin, atezolizumab)

Purpose

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:

      I. 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:

      I. 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:

      I. 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.
    

Trial Arms

NameTypeDescriptionInterventions
Treatment (tretinoin, atezolizumab)ExperimentalPatients 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.
  • Atezolizumab
  • Tretinoin

Eligibility Criteria

        Inclusion Criteria:

          -  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

          -  Absolute neutrophil count (ANC) >= 1,500/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

        Exclusion Criteria:

          -  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

          -  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
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Incidence of adverse events (AEs)
Time Frame:Up to 2 years
Safety Issue:
Description: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.

Secondary Outcome Measures

Measure:Overall response
Time Frame:Up to 2 years
Safety Issue:
Description:Will be calculated and exact binomial 95% confidence interval will be provided.
Measure:Disease control rate
Time Frame:Up to 2 years
Safety Issue:
Description:Will be calculated and exact binomial 95% confidence interval will be provided.
Measure: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
Safety Issue:
Description:Kaplan-Meier methods will be used to estimate OS with 95% confidence interval (CI).
Measure: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
Safety Issue:
Description:Kaplan-Meier methods will be used to estimate PFS with 95% CI.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:Dwight Owen

Last Updated

June 9, 2021