Temozolomide and Atezolizumab as Second or Third Line for the Treatment of Metastatic or Recurrent Small Cell Lung Cancer

G
Greg Durm, MD

Primary Investigator

Enrolling By Invitation
18-100 years
All
Phase 2
56 participants needed
3 Locations

Brief description of study

What is the purpose of this study?
This phase II trial studies the effects of temozolomide and atezolizumab as second or thirdwith small cell lung cancer that has spread to other places inhe body (metastatic) or has come back (recurrent). Chemotherapy drugs, such as temozolomide, work in different ways to stop the growth of tumor cells, either by killing the cells, byg them from dividing, or by stopping them from spreading. Immunotherapy withbodies, such as atezolizumab, may help the body's immune system attack thed may interfere with the ability of tumor cells to grow and spread. Givingzolomide and atezolizumab as second or third line treatment may help prolong survival inwith small cell lung cancer.

PRIMARY OBJECTIVE:
I. To estimate the efficacy of atezolizumab and temozolomide in two dosing schedules forwith metastatic small-cell lung cancer (SCLC) who progress after chemoimmunotherapy.
SECONDARY OBJECTIVES:
I. To evaluate the safety profile and toxicity of combination atezolizumab and temozolomidewo dosing schedules as per Common Terminology Criteria for Adverse Events (CTCAE) version (v) 5.0.
II. To evaluate the progression free survival (PFS) and overall survival (OS) of patientsd with combination atezolizumab and temozolomide.
III. To evaluate the intracranial PFS rate at 6 months (icPFS6) of patients with SCLC treated with atezolizumab and temozolomide.
CORRELATIVE/EXPLORATORY OBJECTIVES:
I. Explore association of myeloid-derived suppressor cell (MDSC) levels at baseline biomarkerus from tumor biopsy samples and peripheral blood and correlate these with clinical(including overall response rate [ORR], OS and toxicity).
II. To evaluate changes in MDSC induced by different dosing of temozolomide. III. To exploredifications of PD-L1 by mass spectrometry.

THIS STUDY IS ENROLLING BY INVITATION ONLY - Consistent with most oncology trials, patients are not actively “recruited,” but are screened by their physician for appropriate clinical trial(s) at the time of their routine clinic visit. Occasionally, a patient may be a self-referral or physician referral, but are still screened for appropriate clinical trials at the time of their routine clinic visit. PI and staff may send copies of relevant consent forms to these patients to look over prior to actually consenting or enrolling them. This may take place at the patient's visit at which the consent is presented or the patient's next visit to the outpatient hematology/oncology clinic.

Interested in participating? For more information about this research study or other cancer-related clinical trials at IU Simon Comprehensive Cancer Center, please contact:
IU Clinical Trials Office 
Phone: (317) 278-5632

Detailed description of study

What will happen during the study?
  • Patients are randomized to 1 of 2 cohorts.
  • COHORT I: Patients receive atezolizumab intravenously (IV) over 30-60 minutes on day 1 andzolomide orally (PO) once daily (QD) on days 1-5. Cycles repeat every 28 days in thebsence of disease progression or unacceptable toxicity.
  • COHORT II: Patients receive atezolizumab IV over 30-60 minutes on day 1. Patients alsove temozolomide PO QD on days 1-14 of cycle 1 and days 1-21 of subsequent cycles. Cyclesvery 28 days in the absence of disease progression or unacceptable toxicity.
  • After completion of study treatment, patients are followed up at 30 days and every 3 monthshereafter.

Eligibility of study

You may be eligible for this study if you meet the following criteria:

  • Conditions: Extensive Stage Lung Small Cell Carcinoma, Metastatic Lung Small Cell Carcinoma, Recurrent Lung Small Cell Carcinoma, Stage IV Lung Cancer AJCC v8, Stage IVA Lung Cancer AJCC v8, Stage IVB Lung Cancer AJCC v8
  • Age: Between 18 Years - 100 Years
  • Gender: All

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 obtainedy
  • Age >= 18 years at the time of consent
  • Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 within 28 daysgistration
  • Have histologically or cytologically-documented diagnosis of extensive stage (i.e.d/or recurrent) small cell lung cancer and have progressed or recurredum-based chemotherapy with immunotherapy. Eligible patients will bedefined as follows:
    • "Sensitive" Disease: Patients who had one previous line of chemotherapy andd after > 90 days of completion of treatment
    • "Resistant" Disease: Patients with no response to first-line chemo-immunotherapygression < 90 days after completing treatment
  • Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST)
    v1.1 within 28 days prior to registration
  • Maximum of 2 prior lines of systemic therapy is allowed in the setting of metastaticdisease. Patients who recur after treatment for limited state disease, and who receivewith chemo-immunotherapy would be considered eligibleupon progression on chemo-IO in the metastatic setting
  • Absolute neutrophil count (ANC) >= 1.5 K/mm^3 (obtained within 28 days prior togistration)
  • Platelets >= 100,000 / mcL (obtained within 28 days prior to registration)
  • Serum creatinine =< 2.0 X upper limit of normal (ULN) OR measured or calculated(glomerular filtration rate [GFR] can also be used in place of[CrCl]) >= 50 mL/min as estimated by Cockcroft andGault formula for subject with creatinine levels > 2 x institutional ULN (obtainedwithin 28 days prior to registration)
  • Bilirubin =< 1.5 X ULN OR direct bilirubin =< ULN for subjects with total bilirubinvels > 1.5 ULN
    • Patients with known Gilbert disease: serum bilirubin =< 3 x ULN) (obtained within28 days prior to registration)
  • Aspartate aminotransferase (AST) and Alanine aminotransferase (ALT) =< 3 X ULN OR =< 5
    X ULN for subjects with liver metastases (obtained within 28 days prior togistration)
  • Albumin > 2.5 g/dL (obtained within 28 days prior to registration)
  • International normalized ratio (INR) or prothrombin time (PT) =< 1.5 x ULN forving therapeutic anticoagulation (obtained within 28 days prior togistration)
    • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  • Activated partial thromboplastin time (aPTT) =< 1.5 x ULN for patients not receiving
    therapeutic anticoagulation (obtained within 28 days prior to registration)
    • For patients receiving therapeutic anticoagulation: stable anticoagulant regimen
  • Females of childbearing potential must have a negative serum or urine pregnancy test
    within 14 days prior to registration
  • For women of childbearing potential: agreement to remain abstinent (refrain fromvaginal intercourse) or use contraceptive methods and agreement to refrain fromdonating 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 ofzolizumab or temozolomide. Women must refrain from donating eggs during thisd
    • Examples of contraceptive methods with a failure rate of < 1% per year includebilateral tubal ligation, male sterilization, hormonal contraceptives thathibit ovulation, hormone releasing intrauterine devices, and copperuterine devices
    • The reliability of sexual abstinence should be evaluated in relation to theduration of the clinical trial and the preferred and usual lifestyle of the. Periodic abstinence (e.g., calendar, ovulation, sympto-thermal, or postvulation methods) and withdrawal are not adequate methods of contraception
  • For men able to father a child: agreement to remain abstinent (refrain from vaginal
    intercourse) or use a condom, and agreement to refrain from donating sperm, as defined
    below
    • With a female partner of childbearing potential or pregnant female partner, menust remain abstinent or use a condom during the treatment period and for 3hs after the final dose of temozolomide to avoid exposing the embryo. Menust refrain from donating sperm during this same period
    • The reliability of sexual abstinence should be evaluated in relation to theduration of the clinical trial and the preferred and usual lifestyle of the. Periodic abstinence (e.g., calendar, ovulation, symptothermal, orvulation methods) and withdrawal are not adequate 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
  • Availability of archival tissue, preferably a recent formalin-fixed, paraffin-embedded(FFPE) tumor tissue block. A recently obtained archival FFPE tumor tissue block from ay or metastatic tumor resection or biopsy can be provided if it was obtainedwithin 1 year of trial screening. Patients with tumor specimens older than 1 year maybe eligible if deemed so by study sponsor. For eligibility, only confirmation ofhival tissue is needed. Verification of tumor burden in the biopsy is encouraged.For optimal biomarker results, tumor content should be > 30% of total tissue area
  • Be willing to provide peripheral blood samples at specified time-points during theudy
  • Life expectancy greater than 3 months as determined by the enrolling physician ordesignee
  • Ability to swallow and retain oral medication
Exclusion Criteria:
  • Is currently participating and receiving study therapy or has participated in a studyvestigational agent and received study therapy or used an investigationaldevice within 4 weeks of the first dose of treatment
  • Has received prior temozolomide therapy
  • Patients with a prior or concurrent malignancy whose natural history or treatment hashe potential to interfere with the safety or efficacy assessment of thevestigational regimen are not eligible for this trial
  • Symptomatic central nervous system (CNS) metastases and/or carcinomatous meningitis.ubjects with asymptomatic lesions will be eligible if considered appropriate by theg physician
    • NOTE: Subjects who are symptomatic and have not undergone prior brain imagingust undergo a head computed tomography (CT) scan or brain MRI within 28 daysgistration to exclude brain metastases
    • NOTE: A subject with prior brain metastasis may be considered if they haved their treatment for brain metastasis at least 2 weeks prior to studygistration, have been off corticosteroids for ≥ 2 weeks, and are asymptomatic
  • Clinically significant acute infection requiring systemic antibacterial, antifungal,
    or antiviral therapy including:
    • Tuberculosis (clinical evaluation that includes clinical history, physicald radiographic findings, and TB testing in line with local)
    • Hepatitis B (known positive HBV surface antigen [HBsAg] result)
    • Hepatitis C, or
    • Human immunodeficiency virus (positive HIV 1/2 antibodies)
    • NOTES: Patients with a past or resolved HBV infection (defined as the presence ofhepatitis B core antibody [anti-HBc] and absence of HBsAg) are eligible. Inwith evidence of chronic hepatitis B virus (HBV) infection, the HBVviral load must be undetectable on suppressive therapy, if indicated. Patientsve for hepatitis C (HCV) antibody are eligible only if polymerase chaingative for HCV ribonucleic acid (RNA). Subjects with HIV/acquiredunodeficiency syndrome (AIDS) with adequate antiviral therapy to control virald (i.e undetectable) would be allowed if they are stable and have been on>= 4 weeks prior to first dose of study drug(s). Subjects withviral hepatitis with controlled viral load would be allowed while on suppressiveviral therapy. Testing not required
  • Has had prior chemotherapy, immunotherapy, targeted small molecule therapy, or
    radiation therapy within 2 weeks prior to study day 1 or who has not recovered (i.e.,=< grade 1 or at baseline) from adverse events due to a previously administered agent
    • Note: Subjects with =< grade 2 neuropathy or alopecia due to chemotherapy are anhis criterion and may qualify for the study
    • Note: If subject received major surgery, they must have recovered adequately fromhe toxicity and/or complications from the intervention prior to starting therapy
    • Note: Subjects with irreversible toxicity that in the opinion of the treatinghysician is not reasonably expected to be exacerbated by the investigationalduct may be included (e.g., hearing loss, hormone deficiency requiringherapy)
  • Active or history of autoimmune disease or immune deficiency, including, but not
    limited to, myasthenia gravis, myositis, autoimmune hepatitis, systemic lupusythematosus, rheumatoid arthritis, inflammatory bowel disease, antiphospholipidbody syndrome, Wegener granulomatosis, Sjogren syndrome, Guillain-Barre syndrome,ultiple sclerosis, with the following exceptions:
    • Replacement therapy (eg., thyroxine, insulin, or physiologic corticosteroidherapy for adrenal or pituitary insufficiency, etc.) is notdered a form of systemic treatment
    • Patients with controlled type 1 diabetes mellitus who are on an insulin regimengible for the study
    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo withdermatologic manifestations only (e.g., patients with psoriatic arthritis areuded) are eligible for the study provided all of following conditions are
      • Rash must cover =< 10% of body surface area
      • Disease is well controlled at baseline and requires only low-potency topicalds
      • No occurrence of acute exacerbations of the underlying condition requiringus ultraviolet A radiation, methotrexate, retinoids, biologicgents, oral calcineurin inhibitors, or high-potency or oral corticosteroidswithin the previous 12 months
  • History of idiopathic pulmonary fibrosis, organizing pneumonia (e.g., bronchiolitis
    obliterans), drug-induced pneumonitis, or idiopathic pneumonitis, or evidence ofve pneumonitis on screening chest computed tomography (CT) scan. History ofdiation pneumonitis in the radiation field (fibrosis) is permitted
  • Significant cardiovascular disease (such as New York Heart Association Class II orgreater cardiac disease, myocardial infarction, or cerebrovascular accident) within 3hs prior to initiation of study treatment, unstable arrhythmia, or unstable angina
  • Has known psychiatric or substance abuse disorders that would interfere withwith the requirements of the trial
  • Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study
  • Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while theher is being treated on study)
  • Has a history or current evidence of any condition, therapy, or laboratory abnormalityhat might confound the results of the trial, interfere with the subject'she full duration of the trial, or is not in the best interest ofhe subject to participate, in the opinion of the treating investigator
  • History of severe allergic anaphylactic reactions to chimeric or humanized antibodiesusion proteins
  • Known hypersensitivity to Chinese hamster ovary cell products or to any component ofhe atezolizumab formulation
  • Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrentdrainage procedures (more than once monthly). Patients with indwelling catheters(e.g., PleurX) are allowed.
  • Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium >12g/dL or corrected serum calcium > ULN)
  • History of leptomeningeal disease

Updated on 01 Aug 2024. Study ID: BTCRC LUN20-462, CTO-BTCRC-LUN20-462, 14973
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