Adjuvant Treatment With Cisplatin-based Chemotherapy Plus Concomitant Atezolizumab in Patients With Stage I (Tumors ≥ 4cm), IIA, IIB, and Select Stage III [Any T1-3 N1-2 and T4N0-2] Resected Non-small Cell Lung Cancer (NSCLC) and the Clearance of Circulating Tumor DNA (ctDNA)

NCT04367311 | Active Not Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: BTCRC-LUN19-396
• Study Type: interventional
• Target: 100
• Locations: 1 country
• Sites: 9

Brief Summary

The vast majority of patients with stage I (tumors ≥ 4cm), IIA, IIB (and select stage III) NSCLC are managed with upfront surgery, followed by adjuvant chemotherapy. However, relapse rates remain high and are primarily due to distant, metastatic disease. Previous meta-analysis evaluating the use of neo-adjuvant chemotherapy and adjuvant chemotherapy demonstrate a similar impact on improved disease free survival (DFS) and overall survival (OS). The role of checkpoint inhibitors has been proven to be effective in the treatment of patients with advanced NSCLC, regardless of histology and PD-L1 expression. Results from trials evaluating the use of checkpoint inhibitors alone or in combination with chemotherapy in the neoadjuvant setting for early stage disease are promising. However, there are no trials evaluating the role of concomitant chemotherapy and checkpoint inhibitors in the adjuvant setting. In addition, emerging data supports the use of ctDNA as a promising biomarker for early detection of minimal residual disease and have indicated that the presence of detectable ctDNA after surgery for localized lung cancer is correlated with a 90-100% chance for disease recurrence. Therefore, we propose this current study assessing concomitant chemotherapy plus Atezolizumab in the adjuvant setting for patients with stage I (tumors ≥ 4cm), IIA, IIB (and select stage III) NSCLC who have detectable ctDNA after surgery. The clearance of ctDNA will serve as a surrogate for long term DFS and OS in this patient population.

Conditions

Lung Cancer; NSCLC

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with undetectable ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab in patients with stage I (tumors ≥ 4cm), IIA, IIB, and select stage III [any T1-3 N1-2 and T4N0-2]

  To estimate the percentage of patients with undetectable circulating tumor DNA (ctDNA) after 4 cycles of adjuvant chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab in patients with stage I (tumors ≥ 4cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC who have detectable ctDNA after surgery, but prior to adjuvant therapy. At each time point, ctDNA detection status (detectable or not detectable) will be determined by CAPP-seq using the Monte Carlo-based ctDNA detection index cutoff point of \< 0.05, as described by Newman et al \[53, 54\]. If ctDNA detection index is \> 0.05, ctDNA will be classified as not detected at that time point, whereas if \< 0.05 then it will be classified as detected.

  Up to 17 cycles (13 months)

Secondary Outcomes (8)

• Percentage of patients with clearance of ctDNA after 4 cycles of adjuvant chemotherapy + Atezolizumab

  4 cycles (3 months)

• Percentage of patients with clearance of ctDNA after 8 cycles (4 cycles of adjuvant chemotherapy + Atezolizumab plus 4 additional cycles of Atezolizumab)

  8 cycles (6 months)

• Percentage of patients with clearance of ctDNA after 12 cycles (4 cycles of adjuvant chemotherapy + Atezolizumab plus 8 additional cycles of Atezolizumab)

  12 cycles (9 months)

• Percentage of patients with clearance of ctDNA during or after adjuvant chemotherapy + Atezolizumab followed by Atezolizumab for up to 13 additional cycles who had no detectable ctDNA after surgery

  Up to 17 cycles (13 months)

• Percentage of pts with clearance of ctDNA after 4 cycles of adj. chemotherapy + Atezolizumab plus up to 13 additional cycles of Atezolizumab

  Up to 17 cycles (13 months)

Study Arms (2)

NSC: Non-squamous cell tumors

EXPERIMENTAL

Atezolizumab 1200mg, Pemetrexed 500 mg/m\^2, Cisplatin 60-75 mg/m\^2

Drug: Atezolizumab; Drug: Cisplatin; Drug: Pemetrexed

SC: Squamous cell tumors

EXPERIMENTAL

Atezolizumab 1200mg, Docetaxel 60-75 mg/m\^2, Cisplatin 60-75 mg/m\^2

Drug: Atezolizumab; Drug: Docetaxel; Drug: Cisplatin

Interventions

Atezolizumab DRUG

Atezolizumab 1200 mg

NSC: Non-squamous cell tumors; SC: Squamous cell tumors

Docetaxel DRUG

Docetaxel 60-75 mg/m\^2

SC: Squamous cell tumors

Cisplatin DRUG

60-75 mg/m\^2

NSC: Non-squamous cell tumors; SC: Squamous cell tumors

Pemetrexed DRUG

Pemetrexed 500mg/m\^2

NSC: Non-squamous cell tumors

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Written informed consent and HIPAA authorization for release of personal health information. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
• Age \>= 18 years at the time of consent.
• ECOG Performance Status of 0-1 within 28 days prior to registration.
• Patients must have undergone complete surgical resection of their stage I (tumors \>= 4cm), IIA, IIB, and select stage III \[any T1-3 N1-2 and T4N0-2\] NSCLC according to the AJCC 8th edition with negative margins (R0).
• Squamous or non-squamous NSCLC histology. Cancers with a histology of "adenosquamous" are considered a type of adenocarcinoma and thus "non-squamous histology".
• Surgery for this lung cancer must be completed \<= 60 days prior to starting treatment.
• Must have tissue available to perform prospective correlative testing. Tissue block is preferred but 10-15 unstained slides (5 μm thick) are also acceptable. If prior PD-L1 results with Dako 22C3 antibody are not available, an additional 5 unstained slides (4 μm thick) must be submitted.
• Demonstrate adequate organ function as defined in the protocol; all screening labs to be obtained within 28 days prior to registration.
• Females of childbearing potential must have a negative serum pregnancy test within 7 days prior to registration NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months
• For women of childbearing potential: agreement to remain abstinent (refrain from heterosexual intercourse) or use contraceptive methods, and agreement to refrain from donating eggs, as defined below:
• Women must remain abstinent or use contraceptive methods with a failure rate of \< 1% per year during the treatment period and for 5 months after the final dose of atezolizumab.
• A woman is considered of childbearing potential if she is postmenarchal, has not reached a postmenopausal state (\> or equal to 12 continuous months of amenorrhea with no identified cause other than menopause), and has not undergone surgical sterilization (removal of ovaries and/or uterus). The definition of childbearing potential may be adapted for alignment with local guidelines or requirements.
• Examples of contraceptive methods with a failure rate of \< 1% per year include bilateral tubal ligation, male sterilization, hormonal contraceptives that inhibit ovulation, hormone-releasing intrauterine devices, and copper intrauterine devices.
• The reliability of sexual abstinence should be evaluated in relation to the duration of the clinical trial and the preferred and usual lifestyle of the patient. Periodic abstinence (e.g., calendar, ovulation, symptothermal, or post-ovulation methods) and withdrawal are not acceptable methods of contraception.
• Contraception method must begin starting from the time of informed consent until 5 months after treatment discontinuation.

You may not qualify if:

• Tumors that have any component of small cell or large cell neuroendocrine histology are NOT eligible.
• Tumors that are known to harbor EGFR mutations or ALK re-arrangements are NOT eligible.
• Prior chemotherapy, radiation therapy, or immunotherapy is NOT allowed for the treatment of this lung cancer.
• Prior chemotherapy and/or radiation therapy is permissible for the treatment of other previous cancers, but must have been completed at least 3 months prior to registration for this trial.
• Other active cancers.
• History of leptomeningeal disease.
• Prior therapy with an anti-PD-1, anti-PD-L1, or anti-PD-L2 agent or with an agent directed to another stimulatory or co-inhibitory T-cell receptor (e.g., CTLA-4, OX-40, CD137).
• Has received a live vaccine within 30 days prior to the first dose of study drug. Examples of live vaccines include, but are not limited to, the following: measles, mumps, rubella, varicella/zoster (chicken pox), yellow fever, rabies, Bacillus Calmette-Guérin (BCG), and typhoid vaccine. Seasonal influenza vaccines for injection are generally killed virus vaccines and are allowed; however, intranasal influenza vaccines (e.g., FluMist®) are live attenuated vaccines and are not allowed.
• Is currently participating in or has participated in a study of an investigational agent or has used an investigational device within 4 weeks prior to the first dose of study treatment.
• Note: Participants who have entered the follow-up phase of an investigational study may participate as long as it has been 4 weeks after the last dose of the previous investigational agent.
• Has a diagnosis of immunodeficiency or is receiving chronic systemic steroid therapy (in dosing exceeding 10 mg daily of prednisone equivalent) or any other form of immunosuppressive therapy within 1 week prior to registration.
• Has severe hypersensitivity (\>= Grade 3) to atezolizumab and/or any of its excipients.
• History of severe allergic anaphylactic reactions to chimeric or humanized antibodies or infusion proteins.
• Has active or history of autoimmune disease or immune deficiency that includes but is not limited to myasthenia gravis, myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener's granulomatosis, Sjögren's syndrome, Guillain-Barré syndrome, or multiple sclerosis.
• Known interstitial lung disease that is symptomatic or may interfere with detection or management of suspected drug-related pulmonary toxicity are not permitted.

Sponsors & Collaborators

• Nasser Hanna: lead
• Genentech, Inc.: collaborator

Study Sites (9)

Northwestern University Feinberg School of Medicine

Chicago, Illinois, 60611, United States

Location

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, 46202, United States

Location

Summit Health

Berkeley Heights, New Jersey, 07922, United States

Location

Rutgers Cancer Institute of New Jersey

New Brunswick, New Jersey, 08903, United States

Location

New York University Clinical Cancer Center

New York, New York, 10016, United States

Location

Ohio State University Comprehensive Cancer Center

Columbus, Ohio, 43210, United States

Location

Penn State Cancer Institute

Hershey, Pennsylvania, 17033, United States

Location

University of Virginia Health System

Charlottesville, Virginia, 22908, United States

Location

University of Wisconsin

Madison, Wisconsin, 53705, United States

Location

MeSH Terms

Conditions

Lung Neoplasms

Interventions

atezolizumab; Docetaxel; Cisplatin; Pemetrexed

Condition Hierarchy (Ancestors)

Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes; Chlorine Compounds; Inorganic Chemicals; Nitrogen Compounds; Platinum Compounds; Guanine; Hypoxanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Glutamates; Amino Acids, Acidic; Amino Acids; Amino Acids, Peptides, and Proteins; Amino Acids, Dicarboxylic

Study Officials

• Nasser Hanna, MD

  Indiana University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Sponsor-Investigator

Study Record Dates

• First Submitted: April 27, 2020
• First Posted: April 29, 2020
• Study Start: May 22, 2020
• Primary Completion: August 6, 2024
• Study Completion: March 1, 2026
• Last Updated: January 2, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (9)