Clinical Trials List
Protocol NumberGO30081
NCT Number(ClinicalTrials.gov Identfier)NCT02763579
Completed
2016-07-01 - 2020-12-31
Others
Terminated3
ICD-10C34
Malignant neoplasm of bronchus and lung
A PHASE III, RANDOMIZED, DOUBLE-BLIND, PLACEBO-CONTROLLED STUDY OF CARBOPLATIN PLUS ETOPOSIDE WITH OR WITHOUT ATEZOLIZUMAB (ANTI−PD-L1 ANTIBODY) IN PATIENTS WITH UNTREATED EXTENSIVE-STAGE SMALL CELL LUNG CANCER
-
Trial Applicant
-
Sponsor
Hoffmann-La Roche
-
Trial scale
Multi-Regional Multi-Center
-
Update
2026/02/01
Investigators and Locations
Co-Principal Investigator
- 蕭慈慧 Division of Thoracic Medicine
- 蔡俊明 Division of Hematology & Oncology
- Heng-Sheng Chao Division of Hematology & Oncology
- Yung-Hung Luo Division of Hematology & Oncology
- 賴信良 Division of Thoracic Medicine
- Chi-Lu Chiang Division of Thoracic Medicine
The Actual Total Number of Participants Enrolled
4 Terminated
Audit
None
Linkou Chang Gung Medical Foundation
Taiwan National PI
楊政達
Co-Principal Investigator
- Wen-Cheng Chang Division of Hematology & Oncology
- Chien-Ying Liu Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- Chih-Hsi Kuo Division of Hematology & Oncology
- Shih-Hong Li Division of Hematology & Oncology
- Chih-Hung Chen Division of Hematology & Oncology
- Chih-Liang Wang Division of Hematology & Oncology
- 枋岳甫 Division of Infectious Disease
The Actual Total Number of Participants Enrolled
3 Terminated
Audit
None
Co-Principal Investigator
- 廖唯昱 Division of Thoracic Medicine
- James Chih-Hsin Yang Division of Hematology & Oncology
- Jih-Hsiang Lee
- JIN-YUAN SHIH Division of Thoracic Medicine
- 許嘉林 Division of Thoracic Medicine
- Chia-Chi Lin Division of Hematology & Oncology
- CHAO-CHI HO CHAO-CHI HO Division of Thoracic Medicine
- 蔡子修 Division of Thoracic Medicine
- 林宗哲 Division of Hematology & Oncology
- 陳冠宇 Division of Thoracic Medicine
- 楊景堯 Division of Thoracic Medicine
- 林育麟 Division of Hematology & Oncology
The Actual Total Number of Participants Enrolled
0 Terminated
Audit
None
Condition/Disease
SMALL CELL LUNG CANCER
Objectives
Primary Efficacy Objectives
The co-primary objectives of this study are the following:
• To evaluate the efficacy of atezolizumab + carboplatin + etoposide compared with
placebo +carboplatin + etoposide in the ITT population as measured by
investigator-assessed PFS according to RECIST v1.1
• To evaluate the efficacy of atezolizumab + carboplatin + etoposide compared with
placebo +carboplatin + etoposide in the ITT population as measured by OS
SAFETY OBJECTIVES
The safety objectives for this study are as follows:
• To evaluate the safety and tolerability of atezolizumab in combination with
carboplatin and etoposide compared with carboplatin and etoposide
• To evaluate the incidence and titers of ATAs against atezolizumab and to explore
the potential relationship of the immunogenicity response with pharmacokinetics,
safety, and efficacy
Test Drug
ATEZOLIZUMAB
Active Ingredient
ATEZOLIZUMAB
Dosage Form
Injection
Dosage
1200mg/20ml
Endpoints
Primary Efficacy Outcome Measures
The primary efficacy outcome measures for this study are:
• PFS, defined as the time from randomization to the first occurrence of disease progression
as determined by the investigator using RECIST v1.1 or death from any cause, whichever
occurs first.
• OS, defined as the time from randomization to death from any cause.
The primary efficacy outcome measures for this study are:
• PFS, defined as the time from randomization to the first occurrence of disease progression
as determined by the investigator using RECIST v1.1 or death from any cause, whichever
occurs first.
• OS, defined as the time from randomization to death from any cause.
Inclution Criteria
Inclusion Criteria
Patients must meet all of the following criteria to be eligible for study entry:
• Signed Informed Consent Form
• Male or female, 18 years of age or older
• ECOG performance status of 0 or 1 (see Appendix 9)
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration
Lung Study Group (VALG) staging system; (Micke et al. 2002; Appendix 3)
• No prior treatment for ES-SCLC
• Patients with a history of treated asymptomatic CNS metastases are eligible,
provided they meet all of the following criteria:
Only supratentorial and cerebellar metastases allowed (i.e., no metastases to
midbrain, pons, medulla or spinal cord)
No ongoing requirement for corticosteroids as therapy for CNS disease
No stereotactic radiation within 7 days
No evidence of interim progression between the completion of CNS-directed
therapy and the screening radiographic study
Patients with new asymptomatic CNS metastases detected at the screening
scan must receive radiation therapy and/or surgery for CNS metastases.
Following treatment, these patients may then be eligible without the need for an
additional brain scan prior to randomization, if all other criteria are met.
• Measurable disease, as defined by RECIST v1.1
Previously irradiated lesions can only be considered as measurable disease if
disease progression has been unequivocally documented at that site since
radiation and the previously irradiated lesion is not the only site of disease.
• Adequate hematologic and end organ function, defined by the following laboratory
results obtained within 14 days prior to randomization:
ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
Lymphocyte count ≥ 500/μL
Platelet count ≥ 100,000/μL without transfusion
Hemoglobin ≥ 9.0 g/dL
Patients may be transfused to meet this criterion.
INR or aPTT ≤ 1.5 × upper limit of normal (ULN)
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be
on a stable dose.
AST, ALT, and alkaline phosphatase ≤ 2.5 ×ULN, with the following exceptions:
Patients with documented liver metastases: AST and/or ALT ≤ 5 ×ULN
Patients with documented liver or bone metastases: alkaline phosphatase
≤ 5 ×ULN.
Serum bilirubin ≤ 1.25 ×ULN
Patients with known Gilbert disease who have serum bilirubin level
≤ 3 ×ULN may be enrolled.
Serum creatinine ≤ 1.5 ×ULN
• Patients must submit a pre-treatment tumor tissue sample during the study. Any
available tumor tissue sample can be submitted. The tissue sample may be
submitted after enrollment.
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of < 1% per year during the treatment period and for at least 90 days after the last
dose of study treatment.
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥ 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, established, proper use of 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 postovulation
methods) and withdrawal are not acceptable methods of contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, as defined below:
With female partners of childbearing potential or pregnant female partners, men
must remain abstinent or use a condom during treatment with chemotherapy
(i.e., carboplatin and etoposide) and for at least 6 months after the last dose of
chemotherapy to avoid exposing the embryo.
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 and withdrawal are not acceptable methods of
contraception.
• For enrollment into the China extension cohort, residence in the People’s Republic
of China
Patients must meet all of the following criteria to be eligible for study entry:
• Signed Informed Consent Form
• Male or female, 18 years of age or older
• ECOG performance status of 0 or 1 (see Appendix 9)
• Histologically or cytologically confirmed ES-SCLC (per the Veterans Administration
Lung Study Group (VALG) staging system; (Micke et al. 2002; Appendix 3)
• No prior treatment for ES-SCLC
• Patients with a history of treated asymptomatic CNS metastases are eligible,
provided they meet all of the following criteria:
Only supratentorial and cerebellar metastases allowed (i.e., no metastases to
midbrain, pons, medulla or spinal cord)
No ongoing requirement for corticosteroids as therapy for CNS disease
No stereotactic radiation within 7 days
No evidence of interim progression between the completion of CNS-directed
therapy and the screening radiographic study
Patients with new asymptomatic CNS metastases detected at the screening
scan must receive radiation therapy and/or surgery for CNS metastases.
Following treatment, these patients may then be eligible without the need for an
additional brain scan prior to randomization, if all other criteria are met.
• Measurable disease, as defined by RECIST v1.1
Previously irradiated lesions can only be considered as measurable disease if
disease progression has been unequivocally documented at that site since
radiation and the previously irradiated lesion is not the only site of disease.
• Adequate hematologic and end organ function, defined by the following laboratory
results obtained within 14 days prior to randomization:
ANC ≥ 1500 cells/μL without granulocyte colony-stimulating factor support
Lymphocyte count ≥ 500/μL
Platelet count ≥ 100,000/μL without transfusion
Hemoglobin ≥ 9.0 g/dL
Patients may be transfused to meet this criterion.
INR or aPTT ≤ 1.5 × upper limit of normal (ULN)
This applies only to patients who are not receiving therapeutic
anticoagulation; patients receiving therapeutic anticoagulation should be
on a stable dose.
AST, ALT, and alkaline phosphatase ≤ 2.5 ×ULN, with the following exceptions:
Patients with documented liver metastases: AST and/or ALT ≤ 5 ×ULN
Patients with documented liver or bone metastases: alkaline phosphatase
≤ 5 ×ULN.
Serum bilirubin ≤ 1.25 ×ULN
Patients with known Gilbert disease who have serum bilirubin level
≤ 3 ×ULN may be enrolled.
Serum creatinine ≤ 1.5 ×ULN
• Patients must submit a pre-treatment tumor tissue sample during the study. Any
available tumor tissue sample can be submitted. The tissue sample may be
submitted after enrollment.
• For women of childbearing potential: agreement to remain abstinent (refrain from
heterosexual intercourse) or use contraceptive methods that result in a failure rate
of < 1% per year during the treatment period and for at least 90 days after the last
dose of study treatment.
A woman is considered to be of childbearing potential if she is postmenarcheal,
has not reached a postmenopausal state (≥ 12 continuous months of
amenorrhea with no identified cause other than menopause), and has not
undergone surgical sterilization (removal of ovaries and/or uterus).
Examples of contraceptive methods with a failure rate of < 1% per year include
bilateral tubal ligation, male sterilization, established, proper use of 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 postovulation
methods) and withdrawal are not acceptable methods of contraception.
• For men: agreement to remain abstinent (refrain from heterosexual intercourse) or
use contraceptive measures, as defined below:
With female partners of childbearing potential or pregnant female partners, men
must remain abstinent or use a condom during treatment with chemotherapy
(i.e., carboplatin and etoposide) and for at least 6 months after the last dose of
chemotherapy to avoid exposing the embryo.
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 and withdrawal are not acceptable methods of
contraception.
• For enrollment into the China extension cohort, residence in the People’s Republic
of China
Exclusion Criteria
Exclusion Criteria
Patients who meet any of the criteria below will be excluded from study entry:
• Active or untreated CNS metastases as determined by computed tomography (CT)
or magnetic resonance imaging (MRI) evaluation during screening and prior
radiographic assessments
• Spinal cord compression not definitively treated with surgery and/or radiation or
previously diagnosed and treated spinal cord compression without evidence that
disease has been clinically stable for ≥ 1 week prior to randomization
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or
calcium > 12 mg/dL or corrected serum calcium >ULN)
Patients who are receiving denosumab prior to randomization must be willing
and eligible to discontinue its use and replace it with a bisphosphonate while in
the study.
• Malignancies other than SCLC within 5 years prior to randomization, with the
exception of those with a negligible risk of metastasis or death (e.g., expected
5-year OS > 90%) treated 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, ductal carcinoma in situ
treated surgically with curative intent)
• Women who are pregnant, lactating, or intending to become pregnant during the
study
• History of severe allergic, anaphylactic, or other hypersensitivity reactions
to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese
hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré
syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 11 for
a more comprehensive list of autoimmune diseases)
Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible for this study.
Patients with controlled Type I diabetes mellitus on a stable dose of insulin
regimen are eligible for this study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
excluded) are permitted provided that they meet the following conditions:
Rash must cover less than 10% of body surface area
Disease is well controlled at baseline and only requires low potency topical
steroids
No acute exacerbations of underlying condition within the last 12 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, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Positive test for HIV
• Patients with active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as the presence of hepatitis B core antibody [HBcAb] and absence of
HBsAg) are eligible. HBV DNA must be obtained in these patients prior to
randomization.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is
negative for HCV RNA.
• Active tuberculosis
• Severe infections at the time of enrollment, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction within 3 months prior to
randomization, unstable arrhythmias, or unstable angina
Patients with known coronary artery disease, congestive heart failure not
meeting the above criteria, or left ventricular ejection fraction < 50% must be on
a stable medical regimen that is optimized in the opinion of the treating
physician, in consultation with a cardiologist if appropriate.
• Major surgical procedure other than for diagnosis within 28 days prior to
randomization or anticipation of need for a major surgical procedure during the
course of the study
• Prior allogeneic bone marrow transplantation or solid organ transplant
• 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 for treatment
complications
• Previous anti-cancer therapy for ES-SCLC
• Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days prior to randomization
• Administration of a live, attenuated vaccine within 4 weeks before randomization 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 through May in the Northern Hemisphere and
approximately April through September in the Southern Hemisphere). Patients
must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®)
within 28 days prior to randomization, during treatment or within 90 days
following the last dose of atezolizumab/placebo.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
anti−PD-1, and anti−PD-L1 therapeutic antibodies
• Treatment with systemic immunosuppressive medications (including, but not limited
to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to randomization
Patients who have received acute, low-dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be
enrolled in the study after discussion with and approval by the Medical Monitor.
The use of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic
hypotension, and low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed.
• History of allergic reactions to carboplatin or etoposide
Patients who meet any of the criteria below will be excluded from study entry:
• Active or untreated CNS metastases as determined by computed tomography (CT)
or magnetic resonance imaging (MRI) evaluation during screening and prior
radiographic assessments
• Spinal cord compression not definitively treated with surgery and/or radiation or
previously diagnosed and treated spinal cord compression without evidence that
disease has been clinically stable for ≥ 1 week prior to randomization
• Leptomeningeal disease
• Uncontrolled pleural effusion, pericardial effusion, or ascites requiring recurrent
drainage procedures (once monthly or more frequently)
Patients with indwelling catheters (e.g., PleurX®) are allowed.
• Uncontrolled or symptomatic hypercalcemia (>1.5 mmol/L ionized calcium or
calcium > 12 mg/dL or corrected serum calcium >ULN)
Patients who are receiving denosumab prior to randomization must be willing
and eligible to discontinue its use and replace it with a bisphosphonate while in
the study.
• Malignancies other than SCLC within 5 years prior to randomization, with the
exception of those with a negligible risk of metastasis or death (e.g., expected
5-year OS > 90%) treated 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, ductal carcinoma in situ
treated surgically with curative intent)
• Women who are pregnant, lactating, or intending to become pregnant during the
study
• History of severe allergic, anaphylactic, or other hypersensitivity reactions
to chimeric or humanized antibodies or fusion proteins
• Known hypersensitivity or allergy to biopharmaceuticals produced in Chinese
hamster ovary cells or any component of the atezolizumab formulation
• History of autoimmune disease, including but not limited to myasthenia gravis,
myositis, autoimmune hepatitis, systemic lupus erythematosus, rheumatoid arthritis,
inflammatory bowel disease, vascular thrombosis associated with antiphospholipid
syndrome, Wegener’s granulomatosis, Sjögren’s syndrome, Guillain-Barré
syndrome, multiple sclerosis, vasculitis, or glomerulonephritis (see Appendix 11 for
a more comprehensive list of autoimmune diseases)
Patients with a history of autoimmune-related hypothyroidism on a stable dose
of thyroid replacement hormone may be eligible for this study.
Patients with controlled Type I diabetes mellitus on a stable dose of insulin
regimen are eligible for this study.
Patients with eczema, psoriasis, lichen simplex chronicus, or vitiligo with
dermatologic manifestations only (e.g., patients with psoriatic arthritis would be
excluded) are permitted provided that they meet the following conditions:
Rash must cover less than 10% of body surface area
Disease is well controlled at baseline and only requires low potency topical
steroids
No acute exacerbations of underlying condition within the last 12 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, organizing pneumonia (e.g., bronchiolitis
obliterans), drug-induced pneumonitis, idiopathic pneumonitis, or evidence of active
pneumonitis on screening chest CT scan
History of radiation pneumonitis in the radiation field (fibrosis) is permitted.
• Positive test for HIV
• Patients with active hepatitis B (chronic or acute; defined as having a positive
hepatitis B surface antigen [HBsAg] test at screening) or hepatitis C
Patients with past hepatitis B virus (HBV) infection or resolved HBV infection
(defined as the presence of hepatitis B core antibody [HBcAb] and absence of
HBsAg) are eligible. HBV DNA must be obtained in these patients prior to
randomization.
Patients positive for hepatitis C virus (HCV) antibody are eligible only if PCR is
negative for HCV RNA.
• Active tuberculosis
• Severe infections at the time of enrollment, including but not limited to
hospitalization for complications of infection, bacteremia, or severe pneumonia
• Significant cardiovascular disease, such as New York Heart Association cardiac
disease (Class II or greater), myocardial infarction within 3 months prior to
randomization, unstable arrhythmias, or unstable angina
Patients with known coronary artery disease, congestive heart failure not
meeting the above criteria, or left ventricular ejection fraction < 50% must be on
a stable medical regimen that is optimized in the opinion of the treating
physician, in consultation with a cardiologist if appropriate.
• Major surgical procedure other than for diagnosis within 28 days prior to
randomization or anticipation of need for a major surgical procedure during the
course of the study
• Prior allogeneic bone marrow transplantation or solid organ transplant
• 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 for treatment
complications
• Previous anti-cancer therapy for ES-SCLC
• Treatment with any other investigational agent or participation in another clinical
study with therapeutic intent within 28 days prior to randomization
• Administration of a live, attenuated vaccine within 4 weeks before randomization 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 through May in the Northern Hemisphere and
approximately April through September in the Southern Hemisphere). Patients
must agree not to receive live, attenuated influenza vaccine (e.g., FluMist®)
within 28 days prior to randomization, during treatment or within 90 days
following the last dose of atezolizumab/placebo.
• Prior treatment with CD137 agonists or immune checkpoint blockade therapies,
anti−PD-1, and anti−PD-L1 therapeutic antibodies
• Treatment with systemic immunosuppressive medications (including, but not limited
to prednisone, cyclophosphamide, azathioprine, methotrexate, thalidomide, and
anti−tumor necrosis factor [anti-TNF] agents) within 2 weeks prior to randomization
Patients who have received acute, low-dose, systemic immunosuppressant
medications (e.g., a one-time dose of dexamethasone for nausea) may be
enrolled in the study after discussion with and approval by the Medical Monitor.
The use of inhaled corticosteroids for chronic obstructive pulmonary disease,
mineralocorticoids (e.g., fludrocortisone) for patients with orthostatic
hypotension, and low-dose supplemental corticosteroids for adrenocortical
insufficiency are allowed.
• History of allergic reactions to carboplatin or etoposide
The Estimated Number of Participants
-
Taiwan
15 participants
-
Global
400 participants
