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

Stage III Lung Cancer AJCC v8 Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04310020
• Other study ID #: NCI-2020-01543
• Secondary ID: NCI-2020-01543S1
• Status: Recruiting
• Phase: Phase 2
• Start date: January 13, 2021
• Est. completion date: September 1, 2024

Study information

• Verified date: May 2024
• Source: National Cancer Institute (NCI)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This trial studies the side effects of radiation therapy followed by atezolizumab in treating patients with stage II or III non-small cell lung cancer. Hyperfractionated radiation therapy delivers smaller doses of radiation therapy over time and may kill more tumor 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.

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 CT scan and may undergo 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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 47
• Est. completion date: September 1, 2024
• Est. primary completion date: September 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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 50% 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 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: Absolute neutrophil count (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

Related Conditions & MeSH terms

• Carcinoma
• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Recurrent Lung Non-Small Cell Carcinoma
• Stage II Lung Cancer AJCC v8
• Stage III Lung Cancer AJCC v8
• Unresectable Lung Non-Small Cell Carcinoma

Intervention

Drug:
• Atezolizumab
Given IV

Procedure:
• Biospecimen Collection
Undergo blood sample collection
• Computed Tomography
Undergo CT scan

Radiation:
• Hypofractionated Radiation Therapy
Undergo hypofractionated radiation therapy

Procedure:
• Magnetic Resonance Imaging
Undergo MRI

Locations

Country	Name	City	State
United States	Hawaii Cancer Care - Westridge	'Aiea	Hawaii
United States	Pali Momi Medical Center	'Aiea	Hawaii
United States	Queen's Cancer Center - Pearlridge	'Aiea	Hawaii
United States	The Cancer Center of Hawaii-Pali Momi	'Aiea	Hawaii
United States	University of New Mexico Cancer Center	Albuquerque	New Mexico
United States	Mary Greeley Medical Center	Ames	Iowa
United States	McFarland Clinic - Ames	Ames	Iowa
United States	Mission Cancer and Blood - Ankeny	Ankeny	Iowa
United States	Ascension Saint Elizabeth Hospital	Appleton	Wisconsin
United States	Augusta University Medical Center	Augusta	Georgia
United States	Mount Sinai Comprehensive Cancer Center at Aventura	Aventura	Florida
United States	Beverly Hospital	Beverly	Massachusetts
United States	University of Alabama at Birmingham Cancer Center	Birmingham	Alabama
United States	Illinois CancerCare-Bloomington	Bloomington	Illinois
United States	Bozeman Health Deaconess Hospital	Bozeman	Montana
United States	Montefiore Medical Center - Moses Campus	Bronx	New York
United States	Montefiore Medical Center-Einstein Campus	Bronx	New York
United States	Montefiore Medical Center-Weiler Hospital	Bronx	New York
United States	Ascension Southeast Wisconsin Hospital - Elmbrook Campus	Brookfield	Wisconsin
United States	Lahey Hospital and Medical Center	Burlington	Massachusetts
United States	Illinois CancerCare-Canton	Canton	Illinois
United States	Saint Francis Medical Center	Cape Girardeau	Missouri
United States	Illinois CancerCare-Carthage	Carthage	Illinois
United States	Dayton Physicians LLC-Miami Valley South	Centerville	Ohio
United States	Miami Valley Hospital South	Centerville	Ohio
United States	Centralia Oncology Clinic	Centralia	Illinois
United States	Saint Mary's Hospital	Centralia	Illinois
United States	Jesse Brown Veterans Affairs Medical Center	Chicago	Illinois
United States	University of Illinois	Chicago	Illinois
United States	Ascension Calumet Hospital	Chilton	Wisconsin
United States	Clackamas Radiation Oncology Center	Clackamas	Oregon
United States	Mercy Cancer Center-West Lakes	Clive	Iowa
United States	Mission Cancer and Blood - West Des Moines	Clive	Iowa
United States	Baptist Memorial Hospital and Cancer Center-Collierville	Collierville	Tennessee
United States	Greater Regional Medical Center	Creston	Iowa
United States	Parkland Memorial Hospital	Dallas	Texas
United States	UT Southwestern Simmons Cancer Center - RedBird	Dallas	Texas
United States	UT Southwestern/Simmons Cancer Center-Dallas	Dallas	Texas
United States	Carle at The Riverfront	Danville	Illinois
United States	Dayton Physician LLC - Englewood	Dayton	Ohio
United States	Miami Valley Hospital	Dayton	Ohio
United States	Miami Valley Hospital North	Dayton	Ohio
United States	Premier Blood and Cancer Center	Dayton	Ohio
United States	Cancer Care Specialists of Illinois - Decatur	Decatur	Illinois
United States	Decatur Memorial Hospital	Decatur	Illinois
United States	Porter Adventist Hospital	Denver	Colorado
United States	Broadlawns Medical Center	Des Moines	Iowa
United States	Iowa Lutheran Hospital	Des Moines	Iowa
United States	Iowa Methodist Medical Center	Des Moines	Iowa
United States	Mercy Medical Center - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Des Moines	Des Moines	Iowa
United States	Mission Cancer and Blood - Laurel	Des Moines	Iowa
United States	Marshfield Medical Center-EC Cancer Center	Eau Claire	Wisconsin
United States	Carle Physician Group-Effingham	Effingham	Illinois
United States	Crossroads Cancer Center	Effingham	Illinois
United States	UPMC Hillman Cancer Center Erie	Erie	Pennsylvania
United States	Illinois CancerCare-Eureka	Eureka	Illinois
United States	Parkland Health Center - Farmington	Farmington	Missouri
United States	UPMC Cancer Center at UPMC Horizon	Farrell	Pennsylvania
United States	UT Southwestern/Simmons Cancer Center-Fort Worth	Fort Worth	Texas
United States	Ascension Saint Francis - Reiman Cancer Center	Franklin	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Franklin	Franklin	Wisconsin
United States	Atrium Medical Center-Middletown Regional Hospital	Franklin	Ohio
United States	Illinois CancerCare-Galesburg	Galesburg	Illinois
United States	Addison Gilbert Hospital	Gloucester	Massachusetts
United States	Benefis Sletten Cancer Institute	Great Falls	Montana
United States	UPMC Cancer Centers - Arnold Palmer Pavilion	Greensburg	Pennsylvania
United States	Miami Valley Cancer Care and Infusion	Greenville	Ohio
United States	Hawaii Cancer Care Inc - Waterfront Plaza	Honolulu	Hawaii
United States	Hawaii Cancer Care Inc-Liliha	Honolulu	Hawaii
United States	Island Urology	Honolulu	Hawaii
United States	Kapiolani Medical Center for Women and Children	Honolulu	Hawaii
United States	Queen's Cancer Cenrer - POB I	Honolulu	Hawaii
United States	Queen's Cancer Center - Kuakini	Honolulu	Hawaii
United States	Queen's Medical Center	Honolulu	Hawaii
United States	Straub Clinic and Hospital	Honolulu	Hawaii
United States	The Cancer Center of Hawaii-Liliha	Honolulu	Hawaii
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	NEA Baptist Memorial Hospital and Fowler Family Cancer Center - Jonesboro	Jonesboro	Arkansas
United States	Kalispell Regional Medical Center	Kalispell	Montana
United States	Illinois CancerCare-Kewanee Clinic	Kewanee	Illinois
United States	Cancer Centers of Southwest Oklahoma Research	Lawton	Oklahoma
United States	Saint Joseph Hospital	Lexington	Kentucky
United States	Saint Joseph Hospital East	Lexington	Kentucky
United States	Saint Joseph Radiation Oncology Resource Center	Lexington	Kentucky
United States	Wilcox Memorial Hospital and Kauai Medical Clinic	Lihue	Hawaii
United States	Littleton Adventist Hospital	Littleton	Colorado
United States	Illinois CancerCare-Macomb	Macomb	Illinois
United States	Marshfield Medical Center-Marshfield	Marshfield	Wisconsin
United States	Carle Physician Group-Mattoon/Charleston	Mattoon	Illinois
United States	Baptist Memorial Hospital and Cancer Center-Memphis	Memphis	Tennessee
United States	Ascension Columbia Saint Mary's Hospital Ozaukee	Mequon	Wisconsin
United States	Mount Sinai Medical Center	Miami Beach	Florida
United States	Ascension Columbia Saint Mary's Hospital - Milwaukee	Milwaukee	Wisconsin
United States	Ascension Saint Francis Hospital	Milwaukee	Wisconsin
United States	Ascension Southeast Wisconsin Hospital - Saint Joseph Campus	Milwaukee	Wisconsin
United States	Marshfield Clinic-Minocqua Center	Minocqua	Wisconsin
United States	Saint Alphonsus Cancer Care Center-Nampa	Nampa	Idaho
United States	UPMC Hillman Cancer Center - New Castle	New Castle	Pennsylvania
United States	CTCA at Southeastern Regional Medical Center	Newnan	Georgia
United States	Cancer Care Center of O'Fallon	O'Fallon	Illinois
United States	HSHS Saint Elizabeth's Hospital	O'Fallon	Illinois
United States	University of Oklahoma Health Sciences Center	Oklahoma City	Oklahoma
United States	Ascension Mercy Hospital	Oshkosh	Wisconsin
United States	Illinois CancerCare-Ottawa Clinic	Ottawa	Illinois
United States	Parker Adventist Hospital	Parker	Colorado
United States	Lahey Medical Center-Peabody	Peabody	Massachusetts
United States	Illinois CancerCare-Pekin	Pekin	Illinois
United States	Illinois CancerCare-Peoria	Peoria	Illinois
United States	Methodist Medical Center of Illinois	Peoria	Illinois
United States	Illinois CancerCare-Peru	Peru	Illinois
United States	Thomas Jefferson University Hospital	Philadelphia	Pennsylvania
United States	University of Pittsburgh Cancer Institute (UPCI)	Pittsburgh	Pennsylvania
United States	UPMC-Saint Clair Hospital Cancer Center	Pittsburgh	Pennsylvania
United States	UPMC-Saint Margaret	Pittsburgh	Pennsylvania
United States	UPMC-Shadyside Hospital	Pittsburgh	Pennsylvania
United States	Oregon Health and Science University	Portland	Oregon
United States	Providence Portland Medical Center	Portland	Oregon
United States	Providence Saint Vincent Medical Center	Portland	Oregon
United States	Illinois CancerCare-Princeton	Princeton	Illinois
United States	Ascension All Saints Hospital	Racine	Wisconsin
United States	Marshfield Medical Center-Rice Lake	Rice Lake	Wisconsin
United States	UT Southwestern Clinical Center at Richardson/Plano	Richardson	Texas
United States	Delbert Day Cancer Institute at PCRMC	Rolla	Missouri
United States	Mercy Clinic-Rolla-Cancer and Hematology	Rolla	Missouri
United States	University of California Davis Comprehensive Cancer Center	Sacramento	California
United States	Missouri Baptist Medical Center	Saint Louis	Missouri
United States	Sainte Genevieve County Memorial Hospital	Sainte Genevieve	Missouri
United States	University of Texas Health Science Center at San Antonio	San Antonio	Texas
United States	UPMC Cancer Center at UPMC Northwest	Seneca	Pennsylvania
United States	Baptist Memorial Hospital and Cancer Center-Desoto	Southhaven	Mississippi
United States	Memorial Medical Center	Springfield	Illinois
United States	Mercy Hospital Springfield	Springfield	Missouri
United States	Southern Illinois University School of Medicine	Springfield	Illinois
United States	Springfield Clinic	Springfield	Illinois
United States	Marshfield Medical Center-River Region at Stevens Point	Stevens Point	Wisconsin
United States	Missouri Baptist Sullivan Hospital	Sullivan	Missouri
United States	BJC Outpatient Center at Sunset Hills	Sunset Hills	Missouri
United States	Dayton Physicians LLC - Troy	Troy	Ohio
United States	Upper Valley Medical Center	Troy	Ohio
United States	Carle Cancer Center	Urbana	Illinois
United States	The Carle Foundation Hospital	Urbana	Illinois
United States	Illinois CancerCare - Washington	Washington	Illinois
United States	UPMC Cancer Center-Washington	Washington	Pennsylvania
United States	UPMC Washington Hospital Radiation Oncology	Washington	Pennsylvania
United States	Ascension Medical Group Southeast Wisconsin - Mayfair Road	Wauwatosa	Wisconsin
United States	Mercy Medical Center-West Lakes	West Des Moines	Iowa
United States	Methodist West Hospital	West Des Moines	Iowa
United States	Marshfield Medical Center - Weston	Weston	Wisconsin
United States	Winchester Hospital	Winchester	Massachusetts

Sponsors (1)

Lead Sponsor	Collaborator
National Cancer Institute (NCI)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of grade 3-5 adverse events	Individual 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.	From baseline, until 180 days from Step 2 registration
Secondary	Incidence of adverse events	Individual 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.	Up to 3 years
Secondary	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)	Binary endpoints will be summarized as proportions with 95% Clopper-Pearson confidence intervals.	After atezolizumab treatment
Secondary	Response rate (confirmed and unconfirmed, complete and partial by RECIST 1.1) in the subset of patients with measurable disease (Registration Step 1)	Binary endpoints will be summarized as proportions with 95% Clopper-Pearson confidence intervals.	During radiation therapy
Secondary	Progression-free survival	Estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.	From 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 years
Secondary	Overall survival	Estimated using the method of Kaplan-Meier. 95% confidence for the medians will be constructed using the method of Brookmeyer-Crowley.	From date of Step 2 registration to date of death due to any cause, assessed up to 3 years