Condition or disease | Intervention/treatment | Phase |
---|---|---|
Non-small Cell Lung Cancer | Drug: Atezolizumab(Tecentriq) Drug: Pemetrexed Drug: Bevacizumab Drug: Carboplatin Drug: Paclitaxel Drug: Carboplatin or cisplatin | Phase 3 |
Study Type : | Interventional (Clinical Trial) |
Estimated Enrollment : | 228 participants |
Allocation: | Randomized |
Intervention Model: | Parallel Assignment |
Masking: | None (Open Label) |
Primary Purpose: | Treatment |
Official Title: | Study of Atezolizumab in Combination With Carboplatin + Paclitaxel +Bevacizumab vs With Pemetrexed + Cisplatin or Carboplatin With Stage IV NON-SQUAMOUS NON-SMALL CELL LUNG CANCER With EGFR(+) or ALK(+) |
Actual Study Start Date : | August 27, 2019 |
Estimated Primary Completion Date : | December 31, 2022 |
Estimated Study Completion Date : | December 31, 2022 |
Arm | Intervention/treatment |
---|---|
Experimental: Atezolizumab group |
Drug: Atezolizumab(Tecentriq)
Atezolizumab(1200 mg IV);Over 60 (± 15) min (for the first infusion); 30 (± 10) min for subsequent infusions if tolerated Frequency: Day 1 of every 21 days Induction: Four or Six Cycles Maintenance : until PD
Drug: Bevacizumab Bevacizumab(15 mg/kg IV);Over 90 (±15) min (for the first infusion); shortening to 60 (± 10) then 30 (± 10) min for subsequent infusions if tolerated
Drug: Carboplatin Carboplatin(AUC 5 or 5.5 IV a); Over approximately 15-30 min
Drug: Paclitaxel Paclitaxel(175 mg/m2 IV); Over 3 hours
|
Active Comparator: Control group |
Drug: Pemetrexed
Induction Period (Four or Six Cycles) (1) Pemetrexed(500 mg/m2 IV); Over approximately10 minutes on Day 1 q3w Maintenance Period (Until PD) Pemetrexed(500 mg/m2 IV); Over approximately10 minutes on Day 1 q3w Drug: Carboplatin or cisplatin Carboplatin(AUC 5.5 IV);Over approximately 30-60 minutes on Day 1 q3W or Cisplatin(75 mg/m²) ; Over 1-2 hours on Day 1 q3w
|
Ages Eligible for Study: | 18 Years and older (Adult, Older Adult) |
Sexes Eligible for Study: | All |
Accepts Healthy Volunteers: | No |
Inclusion Criteria
If the patients have identified T790M mutation after 1st or 2nd generation EGFR TKI failure, the patient must be treated with the second line 3rd generation EGFR TKI treatment, such as osimertinib, before the study participation.
Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene.
Patients with unknown EGFR and/or ALK status require test results at screening. ALK and/or EGFR may be assessed locally or at a main investigator laboratory.
Inoperable stage III non-squamous NSCLC treatment, no prior cytotoxic treatment is allowed and the patients treated with below tyrosine kinase inhibitor prior to the enrollment
No ongoing requirement for corticosteroids as therapy for Central Nervous System(CNS) disease No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization No evidence of interim progression between the completion of Central Nervous System(CNS)-directed therapy and the screening radiographic study
( in case, if patient cannot provides any slides, the enrollment can still be considered with individual discussion with the principal investigator)
- Biopsy and blood sample requirement are as follows for the Whole exome and transcriptome sequencing: A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or 10 or more unstained, freshly cut, serial sections on slides from an FFPE tumor specimen is required for participation in this study. If fewer than 10 slides are available, patient can be still considered for the enrollment based on the discussion and the decision with the principal investigator. This specimen must be accompanied by the associated pathology report.
Fine-needle aspiration (defined as samples that do not preserve tissue architecture and yield cell suspension and/or cell smears), brushing, cell pellet specimens (e.g., from pleural effusion, and lavage samples) are not acceptable.
Tumor tissue from bone metastases that is subject to decalcification is not acceptable.
Endobronchial ultrasonographic biopsy samples are not preferred but acceptable. For core needle biopsy specimens, preferably at least three cores embedded in a single paraffin block, should be submitted for evaluation.
30ml of peripheral blood sample acquired during the screening period
- 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 x 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 x ULN, with the following exceptions:
Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN.
Serum bilirubin ≤ 1.25 x ULN Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled.
Serum creatinine ≤ 1.5 x ULN
Exclusion Criteria
Patients who meet any of the criteria below will be excluded from study entry. Cancer-Specific Exclusions Active or untreated symptomatic Central Nervous System(CNS) metastases as determined by 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 > 2 weeks prior to randomization Leptomeningeal disease Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period.
Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization.
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 Ca > 12 mg/dL) Patients who are receiving denosumab prior to randomization must be willing and eligible to receive a bisphosphonate instead while in the study.
Malignancies other than NSCLC 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)
Contact: Myung-Ju Ahn, MD | 82-2-3410-3488 | silk.ahn@samsung.com | |
Contact: Kyungui Hwang | 82-70-7014-4155 | ku.hwang@samsung.com |
Korea, Republic of | |
Samsung Medical Center | Recruiting |
Seoul, Gangnamgu, Korea, Republic of, 06351 | |
Contact: Myung-Ju Ahn |
Principal Investigator: | Myung-Ju Ahn, MD | Samsung Medical Center |
Tracking Information | |||||||||
---|---|---|---|---|---|---|---|---|---|
First Submitted Date ICMJE | June 5, 2019 | ||||||||
First Posted Date ICMJE | June 19, 2019 | ||||||||
Last Update Posted Date | January 13, 2021 | ||||||||
Actual Study Start Date ICMJE | August 27, 2019 | ||||||||
Estimated Primary Completion Date | December 31, 2022 (Final data collection date for primary outcome measure) | ||||||||
Current Primary Outcome Measures ICMJE |
progression-free survival, PFS [ Time Frame: through study completion, an average of 1 year ] To evaluate the efficacy of atezolizumab + carboplatin + paclitaxel + bevacizumab as progression-free survival (PFS) according to Response Evaluation Criteria in Solid Tumors (RECIST) Version 1.1 (RECIST v1.1) in the following treatment:Atezolizumab + carboplatin + paclitaxel + bevacizumab versus Pemetrexed + carboplatin or cisplatin
|
||||||||
Original Primary Outcome Measures ICMJE | Same as current | ||||||||
Change History | |||||||||
Current Secondary Outcome Measures ICMJE |
|
||||||||
Original Secondary Outcome Measures ICMJE | Same as current | ||||||||
Current Other Pre-specified Outcome Measures | Not Provided | ||||||||
Original Other Pre-specified Outcome Measures | Not Provided | ||||||||
Descriptive Information | |||||||||
Brief Title ICMJE | Study of Atezolizumab Combination Carboplatin + Paclitaxel + Bevacizumab in EGRF Mutation or ALK Translocation NSCLC | ||||||||
Official Title ICMJE | Study of Atezolizumab in Combination With Carboplatin + Paclitaxel +Bevacizumab vs With Pemetrexed + Cisplatin or Carboplatin With Stage IV NON-SQUAMOUS NON-SMALL CELL LUNG CANCER With EGFR(+) or ALK(+) | ||||||||
Brief Summary | This randomized, Phase III, multicenter, open-label study designed to evaluate the efficacy of Atezolizumab in combination with carboplatin, paclitaxel, bevacizumab compared with treatment with pemetrexed, cisplatin in approximately 228 TKI(tyrosine kinase inhibitor) pre treated patients with Stage IV non squamous non small cell lung cancer with activating EGFR mutation or ALK translocation. | ||||||||
Detailed Description | Not Provided | ||||||||
Study Type ICMJE | Interventional | ||||||||
Study Phase ICMJE | Phase 3 | ||||||||
Study Design ICMJE | Allocation: Randomized Intervention Model: Parallel Assignment Masking: None (Open Label) Primary Purpose: Treatment |
||||||||
Condition ICMJE | Non-small Cell Lung Cancer | ||||||||
Intervention ICMJE |
|
||||||||
Study Arms ICMJE |
|
||||||||
Publications * | Not Provided | ||||||||
* Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline. |
|||||||||
Recruitment Information | |||||||||
Recruitment Status ICMJE | Recruiting | ||||||||
Estimated Enrollment ICMJE |
228 | ||||||||
Original Estimated Enrollment ICMJE | Same as current | ||||||||
Estimated Study Completion Date ICMJE | December 31, 2022 | ||||||||
Estimated Primary Completion Date | December 31, 2022 (Final data collection date for primary outcome measure) | ||||||||
Eligibility Criteria ICMJE |
Inclusion Criteria
If the patients have identified T790M mutation after 1st or 2nd generation EGFR TKI failure, the patient must be treated with the second line 3rd generation EGFR TKI treatment, such as osimertinib, before the study participation. Patients with an anaplastic lymphoma kinase (ALK) fusion oncogene must have experienced disease progression (during or after treatment) or intolerance to treatment with one or more ALK inhibitors (i.e., crizotinib) appropriate for the treatment of NSCLC in patients having an ALK fusion oncogene. Patients with unknown EGFR and/or ALK status require test results at screening. ALK and/or EGFR may be assessed locally or at a main investigator laboratory. Inoperable stage III non-squamous NSCLC treatment, no prior cytotoxic treatment is allowed and the patients treated with below tyrosine kinase inhibitor prior to the enrollment
No ongoing requirement for corticosteroids as therapy for Central Nervous System(CNS) disease No stereotactic radiation within 7 days or whole-brain radiation within 14 days prior to randomization No evidence of interim progression between the completion of Central Nervous System(CNS)-directed therapy and the screening radiographic study
( in case, if patient cannot provides any slides, the enrollment can still be considered with individual discussion with the principal investigator) - Biopsy and blood sample requirement are as follows for the Whole exome and transcriptome sequencing: A representative formalin-fixed paraffin-embedded (FFPE) tumor specimen in paraffin block (preferred) or 10 or more unstained, freshly cut, serial sections on slides from an FFPE tumor specimen is required for participation in this study. If fewer than 10 slides are available, patient can be still considered for the enrollment based on the discussion and the decision with the principal investigator. This specimen must be accompanied by the associated pathology report. Fine-needle aspiration (defined as samples that do not preserve tissue architecture and yield cell suspension and/or cell smears), brushing, cell pellet specimens (e.g., from pleural effusion, and lavage samples) are not acceptable. Tumor tissue from bone metastases that is subject to decalcification is not acceptable. Endobronchial ultrasonographic biopsy samples are not preferred but acceptable. For core needle biopsy specimens, preferably at least three cores embedded in a single paraffin block, should be submitted for evaluation. 30ml of peripheral blood sample acquired during the screening period - 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 x 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 x ULN, with the following exceptions: Patients with documented liver metastases: AST and/or ALT ≤ 5 x ULN Patients with documented liver or bone metastases: alkaline phosphatase ≤ 5 x ULN. Serum bilirubin ≤ 1.25 x ULN Patients with known Gilbert disease who have serum bilirubin level ≤ 3 x ULN may be enrolled. Serum creatinine ≤ 1.5 x ULN
Exclusion Criteria Patients who meet any of the criteria below will be excluded from study entry. Cancer-Specific Exclusions Active or untreated symptomatic Central Nervous System(CNS) metastases as determined by 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 > 2 weeks prior to randomization Leptomeningeal disease Uncontrolled tumor-related pain Patients requiring pain medication must be on a stable regimen at study entry. Symptomatic lesions amenable to palliative radiotherapy (e.g., bone metastases or metastases causing nerve impingement) should be treated prior to randomization. Patients should be recovered from the effects of radiation. There is no required minimum recovery period. Asymptomatic metastatic lesions whose further growth would likely cause functional deficits or intractable pain (e.g., epidural metastasis that is not currently associated with spinal cord compression) should be considered for locoregional therapy, if appropriate, prior to randomization. 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 Ca > 12 mg/dL) Patients who are receiving denosumab prior to randomization must be willing and eligible to receive a bisphosphonate instead while in the study. Malignancies other than NSCLC 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) |
||||||||
Sex/Gender ICMJE |
|
||||||||
Ages ICMJE | 18 Years and older (Adult, Older Adult) | ||||||||
Accepts Healthy Volunteers ICMJE | No | ||||||||
Contacts ICMJE |
|
||||||||
Listed Location Countries ICMJE | Korea, Republic of | ||||||||
Removed Location Countries | |||||||||
Administrative Information | |||||||||
NCT Number ICMJE | NCT03991403 | ||||||||
Other Study ID Numbers ICMJE | 2019-03-027 | ||||||||
Has Data Monitoring Committee | No | ||||||||
U.S. FDA-regulated Product |
|
||||||||
IPD Sharing Statement ICMJE | Not Provided | ||||||||
Responsible Party | Myung-Ju Ahn, Samsung Medical Center | ||||||||
Study Sponsor ICMJE | Samsung Medical Center | ||||||||
Collaborators ICMJE | Not Provided | ||||||||
Investigators ICMJE |
|
||||||||
PRS Account | Samsung Medical Center | ||||||||
Verification Date | January 2021 | ||||||||
ICMJE Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP |