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Chemotherapy and Atezolizumab for Patients With Extensive Stage Small Cell Lung Cancer (SCLC) With Untreated, Asymptomatic Brain Metastases

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04610684
Recruitment Status : Recruiting
First Posted : October 30, 2020
Last Update Posted : September 13, 2022
Sponsor:
Collaborators:
Genentech, Inc.
Duke University
Information provided by (Responsible Party):
Jeffrey Clarke, Hoosier Cancer Research Network

Brief Summary:
This is a single arm, multicenter phase II trial for 60 patients with untreated extensive stage (ES) small cell lung cancer (SCLC) with asymptomatic brain metastases. Subjects will receive 4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) and etoposide (80-100 mg/m2 on Days 1-3). Each cycle equals 21 days. After 4 cycles of induction treatment, subjects will receive atezolizumab maintenance 1200 mg on Day 1 of each 3-week cycle. Subjects will receive treatment until disease progression, unacceptable drug-related toxicity, or withdrawal from study for any reason.

Condition or disease Intervention/treatment Phase
Small-cell Lung Cancer Brain Metastases Drug: Carboplatin Drug: Etoposide Drug: Atezolizumab Phase 2

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Chemotherapy and Atezolizumab for Patients With Extensive Stage Small Cell Lung Cancer (SCLC) With Untreated, Asymptomatic Brain Metastases
Actual Study Start Date : January 5, 2021
Estimated Primary Completion Date : May 2023
Estimated Study Completion Date : May 2024


Arm Intervention/treatment
Experimental: Study Treatment Arm
4 cycles of induction treatment with Atezolizumab (1200 mg on Day 1) combined with carboplatin (5-6 AUC on Day 1) and etoposide (80-100 mg/m2 on Days 1-3). After 4 cycles of induction treatment, subjects will receive atezolizumab maintenance 1200 mg on Day 1 of each 3-week cycle.
Drug: Carboplatin
Carboplatin 5-6 mg/mL/min AUC will be delivered over 30 - 60 minutes intravenously on Day 1 of each 21 day Cycle after completion of atezolizumab. For 4 cycles.
Other Name: paraplatin

Drug: Etoposide
Etoposide 80-100 mg/m2 will be delivered over 60 minutes intravenously on Days 1-3 of each 21 day Cycle after completion of carboplatin (Day 1 only). For 4 cycles.
Other Name: VP-16

Drug: Atezolizumab
Atezolizumab 1200 mg will be delivered over 60 (± 15) minutes intravenously on Day 1 of each 21 day Cycle for 4 cycles then continue as monotherapy maintenance with the same schedule.
Other Name: Imfinzi




Primary Outcome Measures :
  1. Intracranial progression free survival (iPFS) [ Time Frame: 2 years ]
    iPFS is defined as the time from Day 1 of treatment until the criteria for intracranial disease progression is met as defined by RANO-BM or death as a result of any cause, whichever comes first.


Secondary Outcome Measures :
  1. Overall Response Rate (ORR) [ Time Frame: 2 years ]
    ORR will include complete response (CR) + partial response (PR) as determined by RECIST 1.1.

  2. Overall Survival (OS) [ Time Frame: 2 years ]
    OS is defined as the time from Day 1 of treatment until death as a result of any cause.

  3. Frequency and severity of adverse events [ Time Frame: 2 years ]
    Toxicity will be graded by Common Toxicity Criteria for Adverse Events (CTCAE V5).

  4. Extracranial Progression Free Survival (PFS) [ Time Frame: 2 years ]
    Extracranial PFS is defined as the time from Day 1 of treatment until the criteria for extracranial disease progression is met as defined by RECIST 1.1 or death as a result of any cause, whichever comes first.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Written informed consent and HIPAA authorization for release of personal health information prior to registration. NOTE: HIPAA authorization may be included in the informed consent or obtained separately.
  2. Age ≥ 18 years with ability and willingness to provide informed consent.
  3. ECOG Performance Status of 0-2.
  4. Histological confirmation of Small Cell Lung Cancer- Extensive Stage (SCLC) per Veterans Administration Lung Study Group (VALG).
  5. At least one untreated asymptomatic brain metastasis that is measurable by RECIST 1.1 that has not been previously irradiated.
  6. No prior treatment for metastatic disease. EXCEPTION: A single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to enrollment.
  7. Treatment-free for at least 6 months since last chemo/radiotherapy, among those treated (with curative intent) with prior chemo/radiotherapy for limited-stage SCLC.
  8. Any prior cancer treatment must be completed at least 6 months prior to registration and the subject must have recovered from all reversible acute toxic effects of the regimen (other than alopecia) to Grade ≤ 1 or baseline. NOTE: a single cycle of chemotherapy (platinum/etoposide) with or without atezolizumab is allowed within 30 days prior to enrollment. NOTE: Extracranial radiation is allowed.
  9. A concurrent diagnosis of a separate malignancy is allowed if clinically stable and does not require tumor-directed therapy.
  10. Demonstrate adequate organ function as defined in the table below

    • Absolute Neutrophil Count (ANC) ≥ 1.5K/mm3 without GCSF
    • Hemoglobin (Hgb) ≥ 9 g/dL (without transfusion)
    • Lymphocyte Count: ≥ 500/µL
    • Platelet Count: ≥ 100,000/µL without transfusion
    • Calculated creatinine clearance ≥ 50 cc/min OR Serum Cr < 1.5 x institutional ULN
    • Bilirubin ≤ 1.5 × upper limit of normal (ULN)
    • Aspartate aminotransferase (AST) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN with liver metastasis
    • Alanine aminotransferase (ALT) ≤ 2 × ULN without liver metastasis ≤ 5 × ULN with liver metastasis
  11. Females of childbearing potential must have a negative serum pregnancy test within 3 days (72 hours) prior to enrollment. NOTE: Females are considered of childbearing potential unless they are surgically sterile (have undergone a hysterectomy or bilateral oophorectomy) or they are naturally postmenopausal for at least 12 consecutive months.
  12. Females of childbearing potential and males must be willing to abstain from heterosexual activity or to use 2 forms of effective methods of contraception, including at least one method with a failure of < 1% per year, from the time of informed consent until 150 days (5 months) after treatment discontinuation.
  13. Negative hepatitis B surface antigen (HBsAg) test, negative total hepatitis B core antibody (HBcAb) test, or positive total HBcAb test followed by a negative hepatitis B virus (HBV) DNA test. The HBV DNA test will be performed only for patients who have a positive total HBcAb test. Testing required at screening only if results are not known.
  14. Negative hepatitis C virus (HCV) antibody test, or positive HCV antibody test followed by a negative HCV RNA test. 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.
  15. As determined by the enrolling physician or protocol designee, ability of the subject to understand and comply with study procedures.

Exclusion Criteria:

  1. Known active CNS metastases which are symptomatic. CNS metastases are considered asymptomatic if the patient does not require high dose or escalating corticosteroids or anticonvulsant therapy. Steroid dose must be equivalent to 2 mg of dexamethasone or less daily.

    • Prior steroid use as part of an anti-emetic regimen with chemotherapy is allowed.
    • Patients must be on a stable dose of corticosteroid. No tapering or decreasing dose within 7 days of enrollment.
  2. Leptomeningeal disease. Discrete dural-based metastases will be allowed without evidence of leptomeningeal disease.
  3. Radiation therapy within 14 days prior to Day 1 of Cycle 1 Day 1. NOTE: Extracranial radiation is allowed.
  4. Uncontrolled or symptomatic hypercalcemia (ionized calcium > 1.5 mmol/L, calcium > 12 mg/dL or corrected serum calcium > ULN)
  5. Known auto-immune conditions requiring systemic immune suppression therapy other than prednisone < 10 mg daily (or equivalent).
  6. History of interstitial pneumonitis from any cause.
  7. Concurrent severe and/or uncontrolled medical conditions which may compromise participation in the study as assessed by site investigator.
  8. Current active infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment on Cycle 1 Day 1. Patients receiving prophylactic antibiotics (e.g., for prevention of urinary tract infection or chronic obstructive pulmonary disease) are eligible. NOTE: Subjects with active tuberculosis are NOT eligible.
  9. Current use of medications specified by the protocol as prohibited for administration in combination with the study drugs. This includes patients with a condition requiring systemic treatment with either corticosteroids (>10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days prior to Cycle 1 Day 1. Inhaled or topical steroids and adrenal replacement doses >10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. Patients who are receiving denosumab prior to enrollment must be willing and eligible to receive a bisphosphonate instead.
  10. History of myocardial infarction, NYHA class II or greater congestive heart failure, or unstable angina, cardiac or other vascular stenting, angioplasty, or surgery within 6 months prior to study enrollment.
  11. Known history of HIV seropositivity or known acquired immunodeficiency syndrome (AIDS), Testing not required at screening.
  12. Requirement for ongoing anticoagulation with heparin, low molecular weight heparin, or other oral anticoagulant (coumadin, DOAC).
  13. Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent drainage procedures (once monthly or more frequently). NOTE: Patients with indwelling catheters (e.g., PleurX®) are allowed.
  14. History of severe allergic, anaphylactic, or other hypersensitivity reactions to chimeric or humanized antibodies or fusion proteins.
  15. Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese hamster ovary cells or any component of the atezolizumab formulation.
  16. History of allergic reactions to carboplatin or etoposide.
  17. Intolerance of atezolizumab or other PD-1/PD-L1 axis drug(s), or any other antibody or drug specifically targeting T-cell co-stimulation or immune checkpoint pathways, including prior therapy with anti-tumor vaccines or other immune-stimulatory anti-tumor agents.
  18. Active or history of autoimmune disease or immune deficiency, including, but not limited to, myasthenia gravis, myositis, autoimmune hepatitis, inflammatory bowel disease, antiphospholipid antibody syndrome, Wegener granulomatosis, Sjögren syndrome, Guillain-Barré syndrome, or multiple sclerosis, with the following exceptions:

    • Patients with a history of autoimmune-related hypothyroidism who are on thyroid-replacement hormone are eligible for the study.
    • Patients with controlled Type 1 diabetes mellitus who are on an insulin regimen are eligible for the study.
    • Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with dermatologic manifestations only (e.g., patients with psoriatic arthritis are excluded) are eligible for the study provided all of following conditions are met:

      • Rash must cover < 10% of body surface area
      • Disease is well controlled at baseline and requires only low-potency topical corticosteroids
      • There has been no occurrence of acute exacerbations of the underlying condition requiring psoralen plus ultraviolet A radiation, methotrexate, retinoids, biologic agents, oral calcineurin inhibitors
  19. Treatment with a live, attenuated vaccine within 4 weeks prior to initiation of study treatment, or anticipation of need for such a vaccine during atezolizumab treatment or within 5 months after the final dose of atezolizumab.
  20. Pregnant or breastfeeding (NOTE: breast milk cannot be stored for future use while the mother is being treated on study).
  21. Treatment with any investigational drug within 28 days prior to Cycle 1 Day 1.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04610684


Contacts
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Contact: Jeffrey Clarke, MD 919-681-4768 jeffrey.clarke@duke.edu
Contact: Ahran Lee 317-634-5842 ext 14 Alee@hoosiercancer.org

Locations
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United States, California
City of Hope Recruiting
Duarte, California, United States, 91010
Contact: Alanna Muirhead    626-218-0961    amuirhead@coh.org   
Principal Investigator: Arya Amini, MD         
United States, Illinois
University of Illinois Cancer Center Recruiting
Chicago, Illinois, United States, 60612
Contact: Erin Keating    312-996-9913    keatin13@uic.edu   
Principal Investigator: Sushma Jonna, MD         
United States, Indiana
St. Vincent Anderson Regional Hospital Recruiting
Anderson, Indiana, United States, 46016
Contact: Dee Vester    765-648-4106    Dee.Vester@ascension.org   
Principal Investigator: Praveen Ranaganath, MD         
United States, Nebraska
Nebraska Methodist Hospital Recruiting
Omaha, Nebraska, United States, 68114
Contact: Brianna Conyers    402-354-5162    Brianna.Conyers@nmhs.org   
Principal Investigator: Timothy Dorius, MD         
United States, New Jersey
Summit Health Recruiting
Berkeley Heights, New Jersey, United States, 07922
Contact: Lorena Farrell    973-436-1752    lfarrell@summithealth.com   
Principal Investigator: Karleung Siu, MD         
United States, North Carolina
Duke Cancer Institute Recruiting
Durham, North Carolina, United States, 27710
Contact: Keiana Watkins    919-660-1278    keiana.watkins@duke.edu   
Principal Investigator: Jeffrey Clarke, MD         
Sponsors and Collaborators
Jeffrey Clarke
Genentech, Inc.
Duke University
Investigators
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Principal Investigator: Jeffrey Clarke, MD Duke University
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Responsible Party: Jeffrey Clarke, Sponsor-Investigator, Hoosier Cancer Research Network
ClinicalTrials.gov Identifier: NCT04610684    
Other Study ID Numbers: HCRN LUN19-427
First Posted: October 30, 2020    Key Record Dates
Last Update Posted: September 13, 2022
Last Verified: September 2022
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
Additional relevant MeSH terms:
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Lung Neoplasms
Neoplasm Metastasis
Small Cell Lung Carcinoma
Brain Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Carcinoma, Bronchogenic
Bronchial Neoplasms
Central Nervous System Neoplasms
Nervous System Neoplasms
Brain Diseases
Central Nervous System Diseases
Nervous System Diseases
Carboplatin
Etoposide
Atezolizumab
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Topoisomerase II Inhibitors
Topoisomerase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action