A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing

Launched by NATIONAL CANCER INSTITUTE (NCI) · Oct 3, 2023

Keywords

ClinConnect Summary

This clinical trial is studying a cancer treatment called atezolizumab, which helps the immune system fight certain types of cancer. Researchers are looking to see if lower doses of this drug can be just as effective as standard doses but with fewer side effects. The trial is open to adults aged 18 and older who have specific types of cancer that have either spread locally or to other parts of the body and are eligible for this treatment.

Participants in the trial will receive atezolizumab through an IV in their arm, either alone or with other medications. They will have their blood tested regularly to monitor the drug levels and adjust their treatment based on those results. The study may last up to two years, and participants will have regular check-ups to track their progress. It’s important to know that participants must meet certain health criteria, such as having a well-functioning immune system and not having specific autoimmune conditions. If you're interested in participating or have questions, it’s a good idea to talk with your doctor.

Gender

ALL

Eligibility criteria

• * INCLUSION CRITERIA:
• • Participants with a locally advanced or metastatic pathologically confirmed cancer whose NCI or other study site s (dependent on at which site the participant will be enrolled) Licensed Independent Practitioner (LIP) determined they are candidates for treatment with atezolizumab, either alone or in combination with other FDA-approved drug(s), for example, TMB-high, PDL-1 positive, or other disease states that respond to PD(L)-1 inhibitors. Regimens with atezolizumab alone or in combination with agents that have previously demonstrated safety in published clinical trials may be used. An LIP may be either an MD, DO, PA, or NP and must be qualified for oncologic management per institutional practice.
• • Age \>=18 years old.
• • Measurable disease per RECIST 1.1 criteria.
• • ECOG performance status of 0-2.
• * Participants must have adequate organ and marrow function as defined below:
• • Absolute neutrophil count (ANC) \>=1,200/microliter
• • Hemoglobin \>9.0 g/dL
• • Platelets \>=75,000/microliter
• • Total bilirubin \<= 1.5 mg/dL, except in participants with Gilbert s Syndrome who must have a total bilirubin less than 3.0 mg/dL
• • Aspartate aminotransferase (AST) / Alanine aminotransferase (ALT) \<=2.5 X institutional upper limit of normal (ULN)
• • Creatinine Clearance (CrCl) \>=30 mL/min/1.73 m\^2 (calculated using the Cockcroft-Gault formula).
• • Serum albumin \> 3 g/dL
• • Individuals of child-bearing potential (IOCBP) must agree to use a highly effective method of contraception (hormonal, intrauterine device (IUD), surgical sterilization) for the duration of the study treatment and up to 5 months after the last dose of the atezolizumab (restriction period). NOTE: abstinence, defined as no vaginal heterosexual intercourse within 6 months prior to the treatment initiation and willingness to continue abstinence for restriction period is also acceptable.
• • Individuals who can father children must agree to use an effective method of contraception (barrier, surgical sterilization) at study entry and up to 5 months after the last dose of the atezolizumab.
• • Nursing participants must be willing to discontinue nursing from study treatment initiation through 5 months after atezolizumab treatment discontinuation.
• • Participants with history of human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and have undetectable viral load.
• • Participants with history of chronic hepatitis B virus (HBV) infection must be on suppressive therapy, if indicated, and have undetectable HBV viral load.
• • Participants with history of hepatitis C virus (HCV) infection must have an undetectable HCV viral load.
• • Participants with history of treated brain metastases must have follow-up brain imaging after central nervous system (CNS)-directed therapy with no evidence of progression.
• • Participants with a prior or concurrent malignancy whose natural history or treatment does not have the potential to interfere with the safety or efficacy assessment of the investigational regimen are eligible.
• • All participants must have the ability to understand and willingness to sign a written informed consent.
• EXCLUSION CRITERIA:
• • Participants who have received an investigational agent for treating participants' disease not approved by FDA within 28 days prior to study treatment initiation.
• • Participants who have received immunostimulatory agents, including, but not limited to, IFN-alpha, IFN-gamma, or IL-2, immunosuppressive medications, and any herbal medicines within 1 month prior to study treatment initiation. NOTE: Physiologic doses of systemic steroids (\<= 10 mg prednisone or equivalent) or local (e.g., topical, nasal, intraarticular, inhaled) steroid use is permitted.
• • Prior treatment with CD137 agonists or immune checkpoint blockade therapies, including anti-CTLA-4, anti-PD-1, and anti-PD-L1 therapeutic antibodies.
• * History or risk of autoimmune disease, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome, or multiple sclerosis, with the following exceptions:
• • Participants with a history of autoimmune-related hypothyroidism on a stable dose of thyroid replacement hormone.
• • Participants with controlled Type 1 diabetes mellitus on a stable insulin regimen.
• * Participants with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., participants with psoriatic arthritis would be excluded) are permitted provided all of the following conditions are met:
• • Rash must cover less than 10% of body surface area (BSA)
• • Disease is well controlled at screening and only requiring low potency topical steroids
• • No acute exacerbations of underlying condition within 12 months prior to study treatment initiation (not requiring psoralen plus ultraviolet A radiation \[PUVA\], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids) within 12 months prior to study treatment initiation.
• • Persisting toxicity related to prior therapy of Grade \>1 per Common Terminology Criteria for Adverse Events (CTCAE) v 5.0 unless deemed not clinically significant or irreversible. NOTE: alopecia and sensory neuropathy Grade \<= 2 are acceptable.
• • Participants with prior allogeneic bone marrow transplantation or prior solid organ transplantation.
• • History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or fusion proteins
• • Known hypersensitivity to Chinese hamster ovary cell products or to any component of the atezolizumab formulation
• • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment
• • Treatment with systemic immunostimulatory agents (including, but not limited to, interferon and IL-2) within 4 weeks or 5 drug-elimination half-lives (whichever is longer) prior to initiation of study treatment
• • Active tuberculosis at screening
• • History of idiopathic pulmonary fibrosis, pneumonitis (including drug induced), organizing pneumonia (i.e., bronchiolitis obliterans, cryptogenic organizing pneumonia, etc.), or evidence of active pneumonitis on screening chest computed tomography (CT) scan. Note: History of radiation pneumonitis in the radiation field (fibrosis) is permitted
• • Participants with significant cardiovascular disease (such as New York Heart Association Class II or greater cardiac disease, myocardial infarction, or cerebrovascular accident (https://www.heart.org/en/health-topics/heart-failure/what-isheart-failure/classes-of-heart-failure), unstable arrhythmia, or unstable angina within 3 months prior to study treatment initiation.
• • Pregnancy (confirmed with Beta-Human chorionic gonadotropin (Beta-HCG) serum or urine pregnancy test in IOCBP performed at screening).
• • Uncontrolled intercurrent illness or situation that would limit compliance with study requirements.