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Study of Radiation Therapy Followed by Atezolizumab in Stage II or III Non-small Cell Lung Cancer Patients

A Pilot Study of Hypofractionated Radiotherapy Followed by Atezolizumab Consolidation in Stage II or III NSCLC Patients With Borderline Performance Status

Status
Active, not recruiting
Phases
Phase 2
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04310020
Enrollment
47
Registered
2020-03-17
Start date
2021-01-13
Completion date
2027-06-01
Last updated
2026-08-24

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Lung Non-Small Cell Carcinoma, Stage III Lung Cancer AJCC v8, Stage II Lung Cancer AJCC v8

Brief summary

This phase II trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hypofractionated radiation therapy delivers higher doses of radiation therapy over a shorter period of time and may kill more cancer cells and have fewer side effects. 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. The purpose of this study is to test the safety and effectiveness of radiation therapy followed by atezolizumab and find out what side effects, if any, it has on patient's non-small cell lung cancer.

Detailed description

PRIMARY OBJECTIVE: I. To evaluate the rate of grade 3-5 treatment-related adverse events (TRAEs) in patients who are not candidates for surgery or concurrent chemoradiation and who have either performance status 0-2 and stage II or performance status 2 and stage III non-small cell lung cancer (NSCLC), treated with hypofractionated thoracic radiotherapy followed by atezolizumab. SECONDARY OBJECTIVES: I. To evaluate response rate (confirmed and unconfirmed, complete and partial by Response Evaluation Criteria in Solid Tumors \[RECIST\] 1.1) from Registration Step 2 in the subset of patients with measurable disease. II. To evaluate response rate (confirmed and unconfirmed, complete and partial by RECIST 1.1) during radiation therapy in the subset of patients with measurable disease. III. To evaluate progression free survival (PFS) from Registration Step 2 by RECIST 1.1. IV. To evaluate overall survival (OS) from Registration Step 2. V. To evaluate the frequency and severity of toxicities. ADDITIONAL OBJECTIVE: I. To bank blood and archival tissue for future research. OUTLINE: RADIATION THERAPY: Patients undergo hypofractionated radiation therapy 5 days per week over 3 weeks for 15 fractions in the absence of disease progression or unacceptable toxicity. CONSOLIDATION: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 of each cycle. Cycles repeat every 21 days for up to 12 months (maximum of 17 cycles) in the absence of disease progression or unacceptable toxicity. Patients undergo computed tomography (CT) scan and may undergo magnetic resonance imaging (MRI) throughout the study, as well as blood sample collection on study. After completion of study treatment, patients are followed up at 6 weeks, every 12 months for the 1 year, then every 6 months until 3 years after study start.

Interventions

DRUGAtezolizumab

Given IV

PROCEDUREBiospecimen Collection

Undergo blood sample collection

PROCEDUREComputed Tomography

Undergo CT scan

RADIATIONHypofractionated Radiation Therapy

Undergo hypofractionated radiation therapy

PROCEDUREMagnetic Resonance Imaging

Undergo MRI

Sponsors

National Cancer Institute (NCI)
Lead SponsorNIH

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE

Eligibility

Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No

Inclusion criteria

* REGISTRATION STEP 1: Participants must have pathologic (cytological or histological) proof of non-small cell lung cancer (NSCLC) * REGISTRATION STEP 1: Participants must have stage III NSCLC with Zubrod performance status of 2 or stage II NSCLC with Zubrod performance status of 0-2 * REGISTRATION STEP 1: Participants must not be candidates for surgical resection in the opinion of the treating investigator. Participants whose disease was previously resected must have experienced local or regional recurrence at least 12 months after resection * REGISTRATION STEP 1: Participants must not be candidates for concurrent chemoradiation in the opinion of the treating investigator * REGISTRATION STEP 1: Participants must have measurable or non-measurable disease documented by CT or MRI. Measurable disease must be assessed within 28 days prior to Registration Step 1. Non-measurable disease must be assessed within 42 days prior to Step 1 registration. The CT from a combined positron emission tomography (PET)/CT may be used only if it is of diagnostic quality. All known sites of disease must be assessed and documented on the Baseline Tumor Assessment Form (RECIST 1.1) * REGISTRATION STEP 1: Participants must have an MRI or CT scan of the brain with contrast within 28 days prior to Registration Step 1 * REGISTRATION STEP 1: Participants' disease must fit within the radiation constraints in the opinion of a local radiation oncologist * REGISTRATION STEP 1: Participants may have received prior treatment for their lung cancer, including surgery, chemotherapy, targeted agents, and/or radiation treatment. At least 12 months must have elapsed since last treatment * REGISTRATION STEP 1: Participants may have had prior radiation therapy as long as the irradiated area does not overlap with the radiation field targeted for this study * REGISTRATION STEP 1: Participants must have recovered from any adverse effects of prior major surgery to the satisfaction of the treating physician. Biopsies and central IV access placement are not considered major surgery * REGISTRATION STEP 1: Absolute neutrophil count (ANC) \>= 1500/mcl (obtained within 28 days prior to Registration Step 1) * REGISTRATION STEP 1: Platelet count \>= 100,000/mcl (obtained within 28 days prior to Registration Step 1) * REGISTRATION STEP 1: Hemoglobin \>= 9 grams/dL (obtained within 28 days prior to Registration Step 1) * REGISTRATION STEP 1: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 1) * REGISTRATION STEP 1: Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =\< 2.5 x IULN (obtained within 28 days prior to Registration Step 1) * REGISTRATION STEP 1: Serum creatinine =\< 1.5 x IULN OR measured or calculated creatinine clearance \>= 40 mL/min (obtained within 28 days prior to Registration Step 1) * REGISTRATION STEP 1: Participants must have percent predicted diffusing capacity of the lungs for carbon monoxide (DLCO) of at least 40% documented within 90 days prior to Registration Step 1 * REGISTRATION STEP 1: Patient must not have had a prior history of interstitial lung disease or \> grade 2 (Common Terminology Criteria for Adverse Events \[CTCAE\] version 5) pneumonitis * REGISTRATION STEP 1: Participants must not have active autoimmune disease requiring therapy within the past 6 months * REGISTRATION STEP 1: Participants must not have an active infection requiring therapy * REGISTRATION STEP 1: Participants must be ≥ 18 years old * REGISTRATION STEP 1: Participants must not be pregnant or nursing because atezolizumab has not been studied in pregnant or nursing women and the mechanism of action is expected to cause fetal harm. Women/men of reproductive potential must have agreed to use an effective contraceptive method while on protocol treatment and for five months after last dose of atezolizumab. A woman is considered to be of "reproductive potential" if she has had menses at any time in the preceding 12 consecutive months. In addition to routine contraceptive methods, "effective contraception" also includes heterosexual celibacy and surgery intended to prevent pregnancy (or with a side-effect of pregnancy prevention) defined as a hysterectomy, bilateral oophorectomy or bilateral tubal ligation. However, if at any point a previously celibate patient chooses to become heterosexually active during the time period for use of contraceptive measures outlined in the protocol, he/she is responsible for beginning contraceptive measures * REGISTRATION STEP 1: Participants with known human immunodeficiency virus (HIV) infection must be on effective anti-retroviral therapy and must have undetectable viral load at their most recent viral load test and within 6 months prior to Registration Step 1 * REGISTRATION STEP 1: Patient must be tested for hepatitis B within 28 days prior to Registration Step 1. Patient must not have active (chronic or acute) hepatitis B virus (HBV) infection. Patients may have past or resolved HBV infection. Active HBV is defined as having a positive hepatitis B surface antigen (HBsAg) test. Past or resolved HBV is defined as having a negative HBsAG test and a positive total hepatitis B core antibody (HBcAb) test * REGISTRATION STEP 1: Patients must not have active hepatitis C virus (HCV) infection. Active HCV is defined as having a positive HCV antibody test followed by a positive HCV ribonucleic acid (RNA) test. Patient must have an HCV antibody test within 28 days prior to Registration Step 1. If the HCV antibody test is positive, the patient must also have an HCV quantitative RNA test within 28 days prior to Registration Step 1 * REGISTRATION STEP 1: No other prior malignancy is allowed except for the following: adequately treated basal cell or squamous cell skin cancer, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission, or any other cancer from which the patient has been disease free for three years. Participants with localized prostate cancer who are being followed by an active surveillance program are also eligible * REGISTRATION STEP 1: Participants must be offered optional participation in banking of specimens for future research * REGISTRATION STEP 1: Participants must be informed of the investigational nature of this study and must sign and give written informed consent in accordance with institutional and federal guidelines * REGISTRATION STEP 1: As a part of the Oncology Patient Enrollment Network (OPEN) registration process the treating institution's identity is provided in order to ensure that the current (within 365 days) date of institutional review board approval for this study has been entered in the system * REGISTRATION STEP 2: Participants must be registered to Step 2 within 42 days after completion of radiation treatment. Participants must have received at least 44 Gy of radiation treatment * REGISTRATION STEP 2: Participants must have no evidence of progression per RECIST 1.1 on CT scan of the chest, abdomen, and pelvis performed between 2 and 5 weeks after completion of radiation therapy * REGISTRATION STEP 2: Any toxicities from radiation therapy must have resolved to \< grade 2 * REGISTRATION STEP 2: ANC \>= 1.5 x 10\^3/uL (obtained within 28 days prior to Registration Step 2) * REGISTRATION STEP 2: Platelet count \>= 100 x 10\^3/uL (obtained within 28 days prior to Registration Step 2) * REGISTRATION STEP 2: Hemoglobin \>= 9 grams/dL (obtained within 28 days prior to Registration Step 2) * REGISTRATION STEP 2: Total bilirubin =\< 1.5 x institutional upper limit of normal (IULN) (obtained within 28 days prior to Registration Step 2) * REGISTRATION STEP 2: AST and ALT =\< 2.5 x IULN (obtained within 28 days prior to Registration Step 2) * REGISTRATION STEP 2: Serum creatinine =\< 1.5 x IULN OR measured or calculated creatinine clearance \>= 40 mL/min (obtained within 28 days prior to Registration Step 2) * REGISTRATION STEP 2: Participants must not have received steroids in doses of more than prednisone 10 mg daily or equivalent within 14 days prior to Registration Step 2 * REGISTRATION STEP 2: Participants must not have received a live vaccine within 28 days prior to Registration Step 2

Design outcomes

Primary

MeasureTime frameDescription
Rate of grade 3-5 adverse eventsFrom baseline, until 180 days from Step 2 registrationIndividual toxicities with possible, probable or likely attribution to treatment along with the overall rate of grade 3, 4 or 5 toxicities attributable to treatment will be summarized.

Secondary

MeasureTime frameDescription
Incidence of adverse eventsUp to 3 yearsIndividual toxicities with possible, probable or likely attribution to treatment along with the overall rate of grade 3, 4 or 5 toxicities attributable to treatment will be summarized.
Response rate (confirmed and unconfirmed, complete and partial by Response Evaluation Criteria in Solid Tumors [RECIST] 1.1) in the subset of patients with measurable disease (Registration Step 2)After atezolizumab treatmentBinary endpoints will be summarized as proportions with 95% Clopper-Pearson confidence intervals.
Response rate (confirmed and unconfirmed, complete and partial by RECIST 1.1) in the subset of patients with measurable disease (Registration Step 1)During radiation therapyBinary endpoints will be summarized as proportions with 95% Clopper-Pearson confidence intervals.
Progression-free survivalFrom date of Step 2 registration to date of first documentation of progression or symptomatic deterioration, or death due to any cause, assessed up to 3 yearsEstimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.
Overall survivalFrom date of Step 2 registration to date of death due to any cause, assessed up to 3 yearsEstimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.

Countries

United States

Contacts

PRINCIPAL_INVESTIGATORRaid Aljumaily

SWOG Cancer Research Network

Outcome results

None listed

Source: ClinicalTrials.gov · Data processed: Aug 25, 2026