Trial Title:
A Study of Therapeutic Drug Monitoring-Based Atezolizumab Dosing
NCT ID:
NCT06066138
Condition:
Locally Advanced Alveolar Soft Part Sarcoma
Metastatic Alveolar Soft Part Sarcoma
Locally Advanced Non Small Cell Lung Cancer
Metastatic Non Small Cell Lung Cancer
Locally Advanced Small Cell Lung Cancer
Metastatic Small Cell Lung Cancer
Locally Advanced Hepatocellular Carcinoma
Metastatic Hepatocellular Carcinoma
Locally Advanced Melanoma
Metastatic Melanoma
Conditions: Official terms:
Carcinoma
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Melanoma
Carcinoma, Hepatocellular
Sarcoma
Small Cell Lung Carcinoma
Sarcoma, Alveolar Soft Part
Atezolizumab
Conditions: Keywords:
PD-L1
PD-1
Tecentriq
Immunotherapy
Study type:
Interventional
Study phase:
Phase 1
Overall status:
Not yet recruiting
Study design:
Allocation:
N/A
Intervention model:
Single Group Assignment
Primary purpose:
Treatment
Masking:
None (Open Label)
Intervention:
Intervention type:
Drug
Intervention name:
Atezolizumab
Description:
Atezolizumab administered via IV at either 1,200 mg q3 weeks, or 1,680 mg q4 weeks for
the first 2 doses followed by 850mg q2 weeks or q6 weeks.
Arm group label:
Arm 1
Summary:
Background:
A type of drug called monoclonal antibody immune checkpoint inhibitors are often used in
cancer treatment. These drugs help the body s immune system fight cancer by blocking
proteins that cause cancer cells to grow. One of these drugs (atezolizumab) is approved
to treat certain cancers. Researchers want to find out if lower doses of this drug might
provide the same benefit with fewer adverse effects.
Objective:
To test different doses and timing of atezolizumab for people with cancer.
Eligibility:
People aged 18 years and older with cancer that has spread locally or to other organs.
They must be eligible for treatment with the study drug.
Design:
Participants will be screened. They will have blood tests and imaging scans. They will
provide a sample of tissue from their tumor.
Atezolizumab is administered through a tube attached to a needle inserted into a vein in
the arm. Participants will take this drug alone or combined with other drugs prescribed
for their care.
The first 2 treatments will be done per the FDA recommended dose and schedule. Before
administering the second dose of the study drug, researchers will check the level of the
drug in the participant s blood. Depending on those results, their 3rd dose will be
scheduled 2 to 6 weeks later.
For the 3rd dose of the study drug, participants will switch to the FDA minimum dosage.
Dosages of any other drugs will not change.
Researchers will continue to test the levels of the drug in participants blood before
each treatment for 16 weeks. After that, these levels will be tested every 3 months.
Study treatment may last up to 2 years.
Detailed description:
Background:
- The treatment of many cancers has been revolutionized through the use of monoclonal
antibody immune checkpoint inhibitor drugs, particularly those that block the
interaction of the anti-programmed death-ligand 1 (PD-L1) with the programmed
death-1 (PD-1) receptor.
- Atezolizumab was initially tested in a phase 1a multicenter, dose-escalation, and
dose- expansion study (NCT01375842) which showed that the drug was well tolerated
and produced clinical responses in a variety of tumors.
- The initially approved atezolizumab regimen was 1,200 mg every 3 weeks, but 840 mg
every 2 weeks was added based on the data from the TNBC trial (NCT01375842). This
was taken further by Morrissey et al., who used population pharmacokinetic (PK)
simulations to determine that dosing regimens of 840 mg every 2 weeks and 1,680 mg
every 4 weeks are interchangeable with 1,200 every 3 weeks in terms of efficacy,
leading the Food and Drug Administration (FDA) to expand the dosing regimens for
atezolizumab.
- The standard dosing regimens yield steady-state concentrations greater than 10-fold
above the stated minimum effective concentration of 6 g/mL, to ensure adequate
exposure for all patients, including patients that may experience lower exposure due
to the incidence of anti-drug-antibodies (ADA). Atezolizumab exhibits a flat
exposure- response relationship.
Objective:
-To test the feasibility of reducing drug exposure while maintaining plasma drug
concentration at or above the expected target trough value during a 16-week study period
by using a method for therapeutic drug monitoring of atezolizumab.
Eligibility:
- Age >= 18 years old.
- Participants with a locally advanced or metastatic 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).
- Eastern Cooperative Oncology Group (ECOG) Performance Score of 0-2.
- Adequate organ and marrow function.
Design:
- This is a phase I feasibility study of a therapeutic drug monitoring (TDM)-based
method for atezolizumab dosing.
- The participants will start with FDA approved dose and frequency of atezolizumab
(840 mg every 2 weeks, 1,200 mg every 3 weeks, or 1,680 mg every 4 weeks) selected
by their treating physician for the first two doses of the drug per standard of
care.
- After the second dose, starting at 3rd dose, the dose of the drug will be switched
to 840 mg and will be used going forward in the trial in all participants.
- Prior to each dose, starting at the 2nd dose, a trough will be drawn which will be
by the population PK model to predict the timing of the next dose to maintain the
atezolizumab target trough for each participant specifically. This will be repeated
for the first 16 weeks of treatment.
- After 16 weeks of treatment, the timing of the next dose to maintain the
atezolizumab target trough for each participant will be monitored and adjusted (if
necessary) every 3 months for each participant until 2 years.
Criteria for 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
- Women of child-bearing potential (WOCBP) 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.
Men 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.
- Breastfeeding participants must be willing to discontinue breastfeeding 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-o
f-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 WOCBP performed at screening).
- Uncontrolled intercurrent illness or situation that would limit compliance with
study requirements.
Gender:
All
Minimum age:
18 Years
Maximum age:
120 Years
Healthy volunteers:
No
Locations:
Facility:
Name:
National Institutes of Health Clinical Center
Address:
City:
Bethesda
Zip:
20892
Country:
United States
Contact:
Last name:
National Cancer Institute Referral Office
Phone:
888-624-1937
Start date:
November 17, 2024
Completion date:
November 29, 2026
Lead sponsor:
Agency:
National Cancer Institute (NCI)
Agency class:
NIH
Source:
National Institutes of Health Clinical Center (CC)
Record processing date:
ClinicalTrials.gov processed this data on November 12, 2024
Source: ClinicalTrials.gov page:
https://clinicaltrials.gov/ct2/show/NCT06066138
https://clinicalstudies.info.nih.gov/cgi/detail.cgi?B_001559-C.html
