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Carcinoma, Non-Small-Cell LungPhase 2NCT03102242

Atezolizumab Immunotherapy in Patients With Advanced NSCLC

A Phase 2 study testing Atezolizumab in people with Carcinoma, Non-Small-Cell Lung, run by Alliance Foundation Trials, LLC. at 13 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
Search all trials

Trial summary

Phase II trial of induction immunotherapy with atezolizumab for patients with unresectable stage IIIA and IIIB NSCLC eligible for chemoradiotherapy with curative intent. Read more about this study

Who is it for?
Ages 18 to 99 years
Conditions the study is for
Carcinoma, Non-Small-Cell Lung
What is being tested?
Atezolizumab
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
64 participants
Where
13 sitesUnited States
Study dates
1 Nov 2017to 1 Oct 2022
Phase
Phase 2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 99 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Newly diagnosed stage IIIA/B NSCLC, PS 0-1
  • No active autoimmune disease or uncontrolled infection, normal bone marrow, renal, hepatic function, FEV1 > 1.2L, no significant underlying heart or lung disease
  • Pathologically proven diagnosis of NSCLC
  • Measurable Stage IIIA or IIIB disease
  • Tissue available for PD-L1 testing and for correlative science testing
  • Patients must be considered unresectable or inoperable. Patients with nodal recurrence after surgery for early-stage NSCLC are eligible if the following criteria are met:
Show all 35Show fewer
  • No prior chemotherapy or radiation for this lung cancer.
  • Prior curative-intent surgery at least 3 months prior to the nodal recurrence.
  • Stage III A or B disease with minimum diagnostic evaluation within 6 weeks to include:
  • History/physical examination
  • Contrast enhanced CT of the chest and upper abdomen
  • MRI of the brain with contrast (or CT with contrast if MRI is medically contraindicated)
  • PET/CT
  • If pleural fluid is visible on CT scan thoracentesis to exclude malignancy should be obtained. Patients with effusions that are too small to tap are eligible.
  • Patients must be at least 4 weeks from major surgery and must be fully recovered
  • Age greater than or equal to 18 years.
  • Representative formalin-fixed paraffin-embedded (FFPE) tumor specimens in paraffin blocks or at least 4 unstained slides, with an associated pathology report, for central testing of tumor PD-L1 expression.
  • If an archived tumor block exists, then either the block or at least 4 unstained slides from the block should be submitted. Tumor tissue should be of good quality based on total and viable tumor content, i.e. at least 50 viable tumor cells and intact tissue architecture. Fine needle aspiration, brushing,and lavage samples are not acceptable. If the block is tissue from a core-needle biopsy, then the block should contain tissue from at least three cores to be sufficient for evaluation.
  • Patients who do not have existing (archived) tissue specimens meeting eligibility requirements may undergo a biopsy during the screening period. Acceptable samples include core needle biopsies for deep tumor tissue (minimum of three cores) or excisional, or forceps biopsies for endobronchial or nodal lesions. The tissue should be fixed in formalin and embedded on site and sent as a block.
  • Adequate hematologic and end organ function, defined by the following laboratory results obtained within 14 days prior to the first study treatment (Cycle 1, Day 1):
  • ANC ≥ 1500 cells/µL
  • WBC counts > 2500/µL
  • Lymphocyte count ≥ 300/µL
  • Platelet count ≥ 100,000/µL
  • Hemoglobin ≥ 10.0 g/dL
  • Total bilirubin ≤ 1.5 x upper limit of normal (ULN) with the following exception:
  • Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
  • AST and ALT ≤ 3.0 x ULN
  • Alkaline phosphatase ≤ 2.5 x ULN
  • Serum creatinine ≤ 1.5 x ULN or creatinine clearance ≥ 50 mL/min on the basis of the Cockcroft-Gault glomerular filtration rate estimation:
  • (140 - age) x (weight in kg) x (0.85 if female)/ 72 x (serum creatinine in mg/dL)
  • Measurable disease per RECIST v1.1 (see Appendix 3)
  • For female patients of childbearing potential and male patients with partners of childbearing potential, agreement (by patient and/or partner) to use highly effective form(s) of contraception (i.e., one that results in a low failure rate [< 1% per year] when used consistently and correctly) and to continue its use for 90 days after the last dose of Atezolizumab.
  • Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1
  • INR and aPTT ≤ 1.5 x ULN • This applies only to patients who do not receive therapeutic anticoagulation; patients receiving therapeutic anticoagulation (such as low-molecular-weight heparin or warfarin) should be on a stable dose.

Who cannot join

  • Active autoimmune disease
  • Greater than minimal, exudative, or cytologically positive pleural effusions
  • Involved contralateral hilar nodes
  • 10% weight loss within the past month
  • Known EGFR exon 19 or 21 mutation or ALK rearrangement
  • Prior invasive malignancy (except non-melanomatous skin cancer) unless disease free for a minimum of 3 years; non-invasive conditions such as carcinoma in situ of the breast, localized prostate cancer, carcinoma in situ of the oral cavity, or cervix are all permissible.
Show all 43Show fewer
  • Prior systemic chemotherapy for the study cancer; note that prior chemotherapy for a different cancer is allowable.
  • Prior radiotherapy to the region of the study cancer that would result in overlap of radiation therapy fields.
  • Prior severe infusion reaction to a monoclonal antibody
  • Severe, active co-morbidity, defined as follows:
  • Significant history of uncontrolled cardiac disease; i.e., uncontrolled hypertension, unstable angina, myocardial infarction within the last 6 months, uncontrolled congestive heart failure, and cardiomyopathy with decreased ejection fraction.
  • Acute bacterial or fungal infection requiring intravenous antibiotics at the time of registration or within 2 weeks of cycle 1 day 1.
  • Chronic Obstructive Pulmonary Disease exacerbation or other respiratory illness requiring hospitalization or precluding study therapy within 30 days before registration
  • Hepatic insufficiency resulting in clinical jaundice and/or coagulation defects
  • Acquired Immune Deficiency Syndrome (AIDS) based upon current CDC definition; note, HIV testing is required for entry into this protocol due to the immunologic basis for induction treatment.
  • Pregnancy, lactation, or inability or unwillingness to use medically acceptable forms of contraception if pregnancy is a risk.
  • Any history of allergic reaction to paclitaxel or other taxanes, or to carboplatin;
  • Uncontrolled neuropathy grade 2 or greater regardless of cause.
  • Any approved anticancer therapy, including chemotherapy, hormonal therapy, or radiotherapy, within 3 weeks prior to initiation of study treatment; however, the following are allowed:
  • Hormone-replacement therapy or oral contraceptives ii. Herbal therapy > 1 week prior to Cycle 1, Day 1 (herbal therapy intended as anticancer therapy must be discontinued at least 1 week prior to Cycle 1, Day 1)
  • Known clinically significant liver disease, including active viral, alcoholic, or other hepatitis; cirrhosis; fatty liver; and inherited liver disease
  • Patients with past or resolved hepatitis B infection (defined as having a negative hepatitis B surface antigen [HBsAg] test and a positive anti-HBc [antibody to hepatitis B core antigen] antibody test) are eligible.
  • Patients positive for hepatitis C virus (HCV) antibody are eligible only if polymerase chain reaction (PCR) is negative for HCV RNA.
  • Known hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • Inability to comply with study and follow-up procedures
  • History of active autoimmune disease, including but not limited to systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, vascular thrombosis associated with antiphospholipid syndrome, Wegener's granulomatosis, Sjögren's syndrome, Bell's palsy, Guillain-Barré syndrome, multiple sclerosis, autoimmune thyroid disease, vasculitis, or glomerulonephritis
  • Patients with a history of autoimmune hypothyroidism on a stable dose of thyroid replacement hormone may be eligible.
  • Patients with controlled Type 1 diabetes mellitus on a stable insulin regimen may be eligible.
  • Patients with eczema, psoriasis, lichen simplex chronicus of vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis would be excluded) are permitted provided that they meet the following conditions:
  • Patients with psoriasis must have a baseline ophthalmologic exam to rule out ocular manifestations
  • Rash must cover less than 10% of body surface area (BSA)
  • Disease is well controlled at baseline and only requiring low potency topical steroids (e.g., hydrocortisone 2.5%, hydrocortisone butyrate 0.1%, fluocinolone 0.01%, desonide 0.05%, alcometasone dipropionate 0.05%)
  • No acute exacerbations of underlying condition within the last 6 months (not requiring psoralen plus ultraviolet A radiation [PUVA], methotrexate, retinoids, biologic agents, oral calcineurin inhibitors; high potency or oral steroids)
  • 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
  • Any other diseases, metabolic dysfunction, physical examination finding, or clinical laboratory finding giving reasonable suspicion of a disease or condition that contraindicates the use of an investigational drug or that may affect the interpretation of the results or render the patient at high risk from treatment complications
  • Active tuberculosis
  • Major surgical procedure within 28 days prior to Cycle 1, Day 1 or anticipation of need for a major surgical procedure during the course of the study
  • Administration of a live, attenuated vaccine within 4 weeks before Cycle 1, Day 1 or anticipation that such a live, attenuated vaccine will be required during the study
  • Influenza vaccination should be given during influenza season only (approximately October to March). Patients must not receive live, attenuated influenza vaccine (e.g., FluMist®) within 4 weeks prior to Cycle 1, Day 1 or at any time during the study.
  • Malignancies other than the disease under study within 5 years prior to Cycle 1, Day 1, with the exception of those with a negligible risk of metastasis or death and with expected curative outcome (such as adequately treated carcinoma in situ of the cervix, basal or squamous cell skin cancer, localized prostate cancer treated surgically with curative intent, or ductal carcinoma in situ treated surgically with curative intent) or undergoing active surveillance per standard-of-care management (e.g., chronic lymphocytic leukemia Rai Stage 0, prostate cancer with Gleason score ≤ 6, and prostate-specific antigen [PSA] ≤ 10 mg/mL, etc.)
  • Medication-Related Exclusion Criteria:
  • Prior treatment with anti-PD-1, or anti-PD-L1 therapeutic antibody or pathway targeting agents
  • Treatment with systemic immunostimulatory agents (including but not limited to interferon [IFN]

Trial locations and contacts

13 sites in 1 country.

13 sites in 1 country

United States13 sites

  • Saint Joseph Mercy Hospital

    Ann Arbor, Michigan, 48106

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • EMMC Cancer Care

    Brewer, Maine, 04412

  • University of Virginia Cancer Center

    Charlottesville, Virginia, 22908

  • The University of Chicago Medical Center

    Chicago, Illinois, 60637

  • Ohio State University James Cancer Center

    Columbus, Ohio, 43210

  • Prisma Health Greenville Memorial Hospital

    Greenville, South Carolina, 29605

  • UCSD Moores Cancer Center

    La Jolla, California, 92037

  • Metro MN Community Oncology Research Consortium

    Minneapolis, Minnesota, 55416

  • Mayo Clinic Hospital

    Phoenix, Arizona, 85054

  • Washington University School of Medicine

    St Louis, Missouri, 63110

  • SUNY Upstate Medical University

    Syracuse, New York, 13210

  • Lankenau Medical Center

    Wynnewood, Pennsylvania, 19096

Other trials in United States

About this study

Official title: Phase II Trial of Induction Immunotherapy With Atezolizumab for Patients With Unresectable Stage IIIA and IIIB NSCLC Eligible for Chemoradiotherapy With Curative Intent.

Phase II trial of induction immunotherapy with atezolizumab for patients with unresectable stage IIIA and IIIB NSCLC eligible for chemoradiotherapy with curative intent.

Read the detailed description

This phase II pilot trial will combine neoadjuvant immunotherapy with Atezolizumab q 21 days for 12 weeks with standard chemoradiotherapy with curative intent for good PS patients with unresectable stage IIIA/B NSCLC. Because of the consequences of progression in this curative-intent population, restaging CT scans will be carried out after the first 2 cycles of neoadjuvant therapy. Non progressing patients will complete a total of one year of anti-PDL1 therapy with an interruption during chemoradiotherapy. Patients with evidence of progression at the first restaging evaluation will proceed immediately to chemoradiotherapy if still eligible for curative intent therapy.

Being tested
Atezolizumab
Medical subject headings
Carcinoma, Non-Small-Cell Lung

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • AtezolizumabDrug

    Single arm phase II trial of induction immunotherapy with anti-PD-L1 for patients with unresectable stage III NSCLC and PS 0-1.

Study groups in NCT03102242
Study groupRoleWhat they receive
TreatmentExperimentalInduction immunotherapy: atezolizumab 1200 mg IV q 21 days x 4 cycles. Restaging after cycle 2 and cycle 4 induction: patients with progression of disease (PD) at the post-cycle 2 assessment will stop atezolizumab and go immediately to chemoradiotherapy if still stage III and eligible for curative intent therapy. Chemoradiotherapy: carboplatin AUC = 2 + paclitaxel 50 mg/m2 IV weekly x 6 weeks concurrent with radiation to a total dose of 60 Gy given in 2 Gy fractions daily M-F x 30 fractions Consolidation chemotherapy: Carboplatin AUC = 6 + paclitaxel 200 mg/m2 IV q 21 days x 2 cycles beginning 3-5 weeks after completion of radiation. Adjuvant immunotherapy: atezolizumab 1200 mg IV q 21 days to complete one year of therapy (from start of induction).
Receives: Drug: Atezolizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Disease Control Rate (DCR) After 12 Weeks Induction

    The primary objective of this single arm phase II trial is to determine whether neoadjuvant and adjuvant anti-PD-L1 therapy bracketing standard chemoradiation therapy and consolidation therapy is worthy of further investigation. The primary endpoint will be the disease control rate (DCR) after 12 weeks induction immunotherapy.

    Measured: 12 weeks

Secondary outcomes (5)

  1. Objective Response Rate (ORR)

    Objective response rate (ORR) is the rate of best overall response (complete or partial response) after 12 weeks of neoadjuvant atezolizumab therapy. ORR and its 90% Clopper-Pearson Confidence interval will be estimated.

    Measured: 12 weeks

  2. Median PFS

    Progression-free survival (PFS) is defined as the time from the start of neoadjuvant therapy to disease progression or recurrence (first disease recurrence or death, whichever comes first). The Kaplan-Meier estimator will be used to estimate median PFS and confidence intervals.

    Measured: 38.3 months

  3. Progression Free Survival (PFS) at 12 and 24 Months

    Progression-free survival (PFS) is defined as the time from the start of neoadjuvant therapy to disease progression or recurrence (first disease recurrence or death, whichever comes first). The Kaplan-Meier estimator will be used to estimate median PFS and confidence intervals. A progression occurs when at least one of the following are true:

    1. At least one new malignant lesion, which also includes any lymph node that was normal at baseline (< 1.0 cm short axis) and increased to ≥ 1.0 cm short axis during follow-up.
    2. At least a 20% increase in PBSD (sum of the longest diameter for all target lesions plus the sum of the short axis of all the target lymph nodes at current evaluation) taking as reference the MSD (Section 11.4.1). In addition, the PBSD must also demonstrate an absolute increase of at least 0.5 cm from the MSD.
    3. See Section 11.3.2 for details in regards to the requirements for PD via FDG-PET imaging.

    Measured: 12 and 24 Months

  4. Median OS

    Overall Survival (OS) is defined as the time from the start of neoadjuvant therapy to death. The Kaplan-Meier estimator will be used to estimate median OS.

    Measured: 38.3 Months

  5. Overall Survival at 12 and 24 Months

    Overall Survival (OS) is defined as the time from the start of neoadjuvant therapy to death. The Kaplan-Meier estimator will be used to estimate OS at 12 months and 24 months, and their confidence intervals.

    Measured: 12 and 24 Months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted5 Apr 2017
  2. Study start1 Nov 2017
  3. Primary completion1 Jun 2020
  4. Study completion1 Oct 2022

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
64 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03102242
Sponsor's protocol ID
AFT-16
Status last verified
Apr 2023
First submitted
27 Mar 2017
Last updated
24 May 2023
Data monitoring committee
Yes
FDA-regulated drug
Yes
FDA-regulated device
No
Individual data sharing
No

Publications

  • Rizvi NA, Mazieres J, Planchard D, Stinchcombe TE, Dy GK, Antonia SJ, Horn L, Lena H, Minenza E, Mennecier B, Otterson GA, Campos LT, Gandara DR, Levy BP, Nair SG, Zalcman G, Wolf J, Souquet PJ, Baldini E, Cappuzzo F, Chouaid C, Dowlati A, Sanborn R, Lopez-Chavez A, Grohe C, Huber RM, Harbison CT, Baudelet C, Lestini BJ, Ramalingam SS. Activity and safety of nivolumab, an anti-PD-1 immune checkpoint inhibitor, for patients with advanced, refractory squamous non-small-cell lung cancer (CheckMate 063): a phase 2, single-arm trial. Lancet Oncol. 2015 Mar;16(3):257-65. doi: 10.1016/S1470-2045(15)70054-9. Epub 2015 Feb 20.

    PubMed 25704439

  • Brahmer J, Reckamp KL, Baas P, Crino L, Eberhardt WE, Poddubskaya E, Antonia S, Pluzanski A, Vokes EE, Holgado E, Waterhouse D, Ready N, Gainor J, Aren Frontera O, Havel L, Steins M, Garassino MC, Aerts JG, Domine M, Paz-Ares L, Reck M, Baudelet C, Harbison CT, Lestini B, Spigel DR. Nivolumab versus Docetaxel in Advanced Squamous-Cell Non-Small-Cell Lung Cancer. N Engl J Med. 2015 Jul 9;373(2):123-35. doi: 10.1056/NEJMoa1504627. Epub 2015 May 31.

    PubMed 26028407

  • Reck M, Paz-Ares L. Immunologic checkpoint blockade in lung cancer. Semin Oncol. 2015 Jun;42(3):402-17. doi: 10.1053/j.seminoncol.2015.02.013. Epub 2015 Feb 19.

    PubMed 25965358

  • Tecentriq Package Insert, 06May 2016 http://www.accessdata.fda.gov/drugsatfda_docs/label/2016/761034s000lbl.pdf

  • Johnson DB, Balko JM, Compton ML, Chalkias S, Gorham J, Xu Y, Hicks M, Puzanov I, Alexander MR, Bloomer TL, Becker JR, Slosky DA, Phillips EJ, Pilkinton MA, Craig-Owens L, Kola N, Plautz G, Reshef DS, Deutsch JS, Deering RP, Olenchock BA, Lichtman AH, Roden DM, Seidman CE, Koralnik IJ, Seidman JG, Hoffman RD, Taube JM, Diaz LA Jr, Anders RA, Sosman JA, Moslehi JJ. Fulminant Myocarditis with Combination Immune Checkpoint Blockade. N Engl J Med. 2016 Nov 3;375(18):1749-1755. doi: 10.1056/NEJMoa1609214.

    PubMed 27806233

  • Nishino M, Giobbie-Hurder A, Gargano M, Suda M, Ramaiya NH, Hodi FS. Developing a common language for tumor response to immunotherapy: immune-related response criteria using unidimensional measurements. Clin Cancer Res. 2013 Jul 15;19(14):3936-43. doi: 10.1158/1078-0432.CCR-13-0895. Epub 2013 Jun 6.

    PubMed 23743568

  • Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, Dancey J, Arbuck S, Gwyther S, Mooney M, Rubinstein L, Shankar L, Dodd L, Kaplan R, Lacombe D, Verweij J. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009 Jan;45(2):228-47. doi: 10.1016/j.ejca.2008.10.026.

    PubMed 19097774

  • Ross HJ, Kozono D, Wang XF, Urbanic JJ, Williams TM, Nelson GD, Carbone DP, Chung D, Robb R, Byun WY, Talabere T, DuFrane C, Bara I, Schulze K, Brockman M, Gao J, Vokes EE, Stinchcombe TE. Atezolizumab Before and After Chemoradiation for Unresectable Stage III Non-Small Cell Lung Cancer: A Phase II Nonrandomized Controlled Trial. JAMA Oncol. 2024 Sep 1;10(9):1212-1219. doi: 10.1001/jamaoncol.2024.1897.

    PubMed 39052256

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Atezolizumab in people with Carcinoma, Non-Small-Cell Lung, run by Alliance Foundation Trials, LLC. at 13 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 35 inclusion and 43 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 24 May 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 13 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 24 May 2023). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Disease Control Rate (DCR) After 12 Weeks Induction (time frame: 12 weeks). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03102242, which also lists 8 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 24 May 2023.

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