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Combination Chemotherapy and Atezolizumab for the Treatment of Stage IB-IIIA Non-small Cell Lung Cancer

Trial Status: Active

This phase II trial estimates how many patients with stage IB-IIIA non-small cell lung cancer have measurable circulating tumor deoxyribonucleic acid (ctDNA) in their blood at baseline and unmeasurable ctDNA after receiving 1 year of chemotherapy and atezolizumab. ctDNA is genetic material in the bloodstream that comes from the tumor and is a possible marker of lung cancer returning. Chemotherapy drugs, such as cisplatin, pemetrexed, and docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells, by stopping them from dividing, or by stopping them from spreading. 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. Adding atezolizumab to combination chemotherapy may help kill any remaining cancer cells in patients with non-small cell lung cancer.

Inclusion Criteria

  • Written informed consent and Health Insurance Portability and Accountability Act (HIPAA) authorization for release of personal health information * NOTE: HIPAA authorization may be included in the informed consent or obtained separately
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0-1 within 28 days prior to registration
  • Patients must have undergone complete surgical resection of their stage I (tumors >= 4 cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) NSCLC according to the American Joint Committee on Cancer (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 um thick) are also acceptable. If prior PD-L1 results with Dako 22C3 antibody are not available, an additional 5 unstained slides (4 um thick) must be submitted
  • White blood cell (WBC) >= 1500 K/mm^3 (within 28 days prior to registration)
  • Hemoglobin (Hgb) >= 8 g/dL (within 28 days prior to registration)
  • Platelet count >= 100 K/mm^3 (within 28 days prior to registration)
  • Serum creatinine =< 1.5 x upper limit of normal (ULN) OR calculated creatinine clearance >= 40 mL/min using the Cockcroft-Gault formula (within 28 days prior to registration)
  • Total bilirubin =< 1.5 x ULN (within 28 days prior to registration)
  • Aspartate aminotransferase (AST) =< 1.5 x ULN (within 28 days prior to registration)
  • Alanine aminotransferase (ALT) =< 1.5 x ULN (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 two non-hormonal methods of contraception, including at least one method with a failure rate of < 1% per year, during the treatment period and for 5 months after treatment discontinuation. Examples of non-hormonal 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. Must use “estrogen-free” hormonal method if this is chosen contraception method. A barrier method may be used as the second contraceptive method. 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
  • For men: Agreement to remain abstinent (refrain from heterosexual intercourse) or use a condom, and agreement to refrain from donating sperm, as defined below: * With female partners of childbearing potential or pregnant female partners, men must remain abstinent or use a condom during the treatment period and for 5 months after the last dose of study treatment to avoid exposing the embryo. Men must refrain from donating sperm during this same period * 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
  • As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures for the entire length of the study

Exclusion Criteria

  • 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
  • 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-Guerin (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
  • 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, Sjogren’s syndrome, Guillain-Barre 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
  • Has a history of (non-infectious) pneumonitis that required steroids or has current pneumonitis
  • Has a severe infection within 4 weeks prior to initiation of study treatment, including but not limited to hospitalization for complications of infection, bacteremia, or severe pneumonia
  • Has a known history of human immunodeficiency virus (HIV). Note: HIV testing is not required
  • Has a known history of hepatitis B or known active hepatitis C virus infection. Note: If hepatitis B and hepatitis C status is unknown, testing is required: * Subject must have negative total hepatitis B core antibody (HBcAb) test at screening, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test at screening. The HBV DNA test will be performed only for patients who have a positive total HBcAb test * Subject must have negative hepatitis C virus (HCV) antibody test at screening, or positive HCV antibody test followed by a negative HCV ribonucleic acid (RNA) test at screening. The HCV RNA test will be performed only for patients who have a positive HCV antibody test. A positive HCV RNA test is sufficient to diagnose active HCV infection in the absence of an HCV antibody test
  • Has a known history of active TB (Bacillus tuberculosis)
  • Has a history or current evidence of any condition, therapy, or laboratory abnormality that might confound the results of the study, interfere with the subject’s participation for the full duration of the study, or is not in the best interest of the subject to participate, in the opinion of the treating investigator
  • Has known psychiatric or substance abuse disorders that would interfere with cooperation with the requirements of the trial
  • Is pregnant or breastfeeding or expecting to conceive or father children within the projected duration of the study, starting with the screening visit through 5 months after the last dose of study drug

Indiana

Indianapolis
Indiana University / Melvin and Bren Simon Cancer Center
Status: ACTIVE
Contact: Nasser H. Hanna
Phone: 317-278-6704

New Jersey

New Brunswick
Rutgers Cancer Institute of New Jersey
Status: IN_REVIEW
Contact: Jyoti Malhotra
Phone: 732-235-7521

PRIMARY OBJECTIVE:

I. To estimate the percentage of patients with undetectable circulating tumor deoxyribonucleic acid (DNA) (ctDNA) after 4 cycles of adjuvant chemotherapy + atezolizumab plus up to 13 additional cycles of atezolizumab in patients with stage I (tumors >= 4 cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) non-small cell lung cancer (NSCLC) who have detectable ctDNA after surgery, but prior to adjuvant therapy.

SECONDARY OBJECTIVES:

I. To estimate the percentage of patients with clearance of ctDNA after 4 cycles of adjuvant chemotherapy + atezolizumab in patients with stage I (tumors >= 4 cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) NSCLC who have undergone surgical resection with detectable ctDNA after surgery.

II. To estimate the percentage of patients with clearance of ctDNA after 8 cycles (4 cycles of adjuvant chemotherapy + atezolizumab plus 4 additional cycles of atezolizumab) in patients with stage I (tumors >= 4 cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) NSCLC who have undergone surgical resection with detectable ctDNA after surgery.

III. To estimate the percentage of patients with clearance of ctDNA after 12 cycles (4 cycles of adjuvant chemotherapy + atezolizumab plus 8 additional cycles of atezolizumab) in patients with stage I (tumors >= 4 cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) NSCLC who have undergone surgical resection with detectable ctDNA after surgery.

IV. To estimate the 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.

V. To estimate the percentage of patients with clearance of ctDNA after 4 cycles of adjuvant chemotherapy + atezolizumab plus up to 13 additional cycles of atezolizumab in patients with stage I (tumors >= 4 cm), IIA, IIB, and select IIIA (T3N1, T4N0-1) NSCLC who have undergone surgical resection, regardless of ctDNA status after surgery.

VI. To estimate the 1 year disease-free survival (DFS) in all patients treated on study.

VII. To estimate the 1 year DFS in patients with no detectable ctDNA after 4 cycles of adjuvant chemotherapy + atezolizumab who had detectable ctDNA after surgery.

VIII. To estimate the 1 year DFS in patients with detectable ctDNA after 1 year of adjuvant therapy on study.

CORRELATIVE/EXPLORATORY OBJECTIVE:

I. To collect biofluids and tissue for future biomarker retrospective analysis.

OUTLINE: Patients are assigned to 1 of 2 arms based on histology type.

ARM I (SQUAMOUS CELL TUMORS):

INITIAL THERAPY (CYCLES 1-4): Patients receive atezolizumab intravenously (IV) over 30-60 minutes, docetaxel IV, and cisplatin IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY (CYCLES 5-17): Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

ARM II (NON-SQUAMOUS CELL TUMORS):

INITIAL THERAPY (CYCLES 1-4): Patients receive atezolizumab IV over 30-60 minutes, pemetrexed IV, and cisplatin IV on day 1. Treatment repeats every 21 days for up to 4 cycles in the absence of disease progression or unacceptable toxicity.

MAINTENANCE THERAPY (CYCLES 5-17): Patients receive atezolizumab IV over 30-60 minutes on day 1. Treatment repeats every 21 days for up to 13 cycles in the absence of disease progression or unacceptable toxicity.

After completion of study treatment, patients are followed up at 30 days and then every 3 months until 1 year after initiating study treatment.

Trial Phase Phase II

Trial Type Treatment

Lead Organization
Indiana University / Melvin and Bren Simon Cancer Center

Principal Investigator
Nasser H. Hanna

  • Primary ID CTO-BTCRC-LUN19-396
  • Secondary IDs NCI-2020-04539
  • Clinicaltrials.gov ID NCT04367311