Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202211687583152 Date of Approval: 16/11/2022
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title A Study to Evaluate the Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (B-FAST)
Official scientific title A PHASE II/III MULTICENTER STUDY EVALUATING THE EFFICACY AND SAFETY OF MULTIPLE TARGETED THERAPIES AS TREATMENTS FOR PATIENTS WITH ADVANCED OR METASTATIC NON-SMALL CELL LUNG CANCER (NSCLC) HARBORING ACTIONABLE SOMATIC MUTATIONS DETECTED IN BLOOD (BFAST: BLOOD FIRST ASSAY SCREENING TRIAL)
Brief summary describing the background and objectives of the trial This is a phase 2/3, global, multicenter, open-label, multi-cohort study designed to evaluate the safety and efficacy of targeted therapies or immunotherapy as single agents or in combination in participants with unresectable, advanced or metastatic NSCLC determined to harbor oncogenic somatic mutations or positive by tumor mutational burden (TMB) assay as identified by two blood-based next-generation sequencing (NGS) circulating tumor DNA (ctDNA) assays. Kenya will take part in Cohort F and G. Primary Efficacy Objective: To evaluate the efficacy of alectinib in patients with ALK+ advanced or metastatic NSCLC as determined by the F1LCDX assay. Secondary Efficacy Objective: To evaluate the efficacy of alectinib in patients with ALK+ advanced or metastatic NSCLC as determined by the F1LCDX assay. Corresponding Safety Objective:To evaluate the safety and tolerability of alectinib. PRO Objective: To evaluate the impact of alectinib on PROs in patients with ALK+ advanced or metastatic NSCLC as determined by the F1LCDX assay. PRO Objective: To evaluate and compare patients’ health status to generate utility scores for use in economic models for reimbursement. Biomarker Objective: To assess prognostic effect and pharmacodynamics of exploratory biomarkers in blood, and their association with disease status, mechanisms of resistance, and/or response to alectinib. Exploratory Objective: To explore the anti-tumor effect of alectinib in patients with CNS disease identified at baseline. Exploratory Objective: To evaluate the efficacy of alectinib in patients with ALK+ advanced or metastatic NSCLC as determined by the F1LCDX assay. The corresponding endpoints are outlined in the protocol.
Type of trial CCT
Acronym (If the trial has an acronym then please provide) BFAST
Disease(s) or condition(s) being studied Cancer
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Treatment: Drugs
Anticipated trial start date 17/01/2023
Actual trial start date
Anticipated date of last follow up 27/04/2024
Actual Last follow-up date
Anticipated target sample size (number of participants) 682
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL https://www.clinicaltrials.gov/ct2/show/NCT03178552
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Non-randomised Open-label(Masking Not Used)
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Cohort F Atezolizumab Bevacizumab Carboplatin and Pemetrexed Drug: Atezolizumab Participants will receive atezolizumab 1200 mg IV infusion Q21D (Cohorts C and F) or 1680 mg IV infusion Q4W starting on Day 29 (Cohort E). Other Name: RO5541267 Drug: Pemetrexed Participants will receive pemetrexed 500 mg/m^2 IV infusion on Day 1 Q21D Drug: Carboplatin Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D Drug: Bevacizumab Participants will receive 15 mg/kg of IV bevacizumab on Day 1 of each 21-day cycle during the induction and maintenance periods Other Name: RO4876646 This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days) This cohort includes participants with EGFR exon 20+ NSCLC. Participants will receive atezolizumab + bevacizumab + carboplatin + pemetrexed for 4 or 6 induction cycles (cycle = 21 days). After induction therapy, participants will continue maintenance treatment with atezolizumab + bevacizumab + pemetrexed until disease progression, unacceptable toxicity, withdrawal of consent, or death 80
Experimental Group Cohort G GDC 6036 This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD until disease progression or unacceptable toxicity. Drug: GDC-6036 Participants will receive GDC-6036 PO QD until disease progression or unacceptable toxicity. Other Name: RO7435846 All cycles will be 21 days in length. This cohort includes participants with KRAS G12C mutation. Participants will receive GDC-6036 PO QD until disease progression or unacceptable toxicity 301
Control Group Cohort G Docetaxel This cohort includes participants with KRAS G12C mutation. Participants will receive IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity. Drug: Docetaxel Participants will receive IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity All cycles will be 21 days in length. This cohort includes participants with KRAS G12C mutation. Participants will receive IV docetaxel Q3W (75 mg/m^2) until disease progression or unacceptable toxicity. 301 Active-Treatment of Control Group
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
-Histologically or cytologically confirmed diagnosis of unresectable Stage IIIb not amenable to treatment with combined modality chemoradiation (advanced) or Stage IV (metastatic) NSCLC -Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2 -Measurable disease -Adequate recovery from most recent systemic or local treatment for cancer -Adequate organ function -Life expectancy greater than or equal to (>/=) 12 weeks -For female participants of childbearing potential and male participants, willingness to use acceptable methods of contraception -Inability to swallow oral medication -Women who are pregnant or lactating -Symptomatic, untreated CNS metastases -History of malignancy other than NSCLC within 5 years prior to screening with the exception of malignancies with negligible risk of metastasis or death -Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction, or cerebrovascular accident within 3 months prior to randomization, unstable arrhythmias, or unstable angina -Known human immunodeficiency virus (HIV) positivity or autoimmune deficiency syndrome (AIDS)-related illness -Either a concurrent condition or history of a prior condition that places the patient at unacceptable risk if he/she were treated with the study drug or confounds the ability to interpret data from the study -Inability to comply with other requirements of the protocol 80 and over: 80+ Year,Adult: 19 Year-44 Year,Aged: 65+ Year(s),Middle Aged: 45 Year(s)-64 Year(s) 18 Year(s) 100 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 14/10/2022 Institutional Scientific and Ethics Review Committee ISERC Aga Khan University Hospital Nairobi
Ethics Committee Address
Street address City Postal code Country
3rd Parklands Avenue, Off Limuru Road Nairobi 00100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome Cohort F: Investigator-Assessed Objective Response Rate (ORR) Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] Cohort G: PFS as Determined by Blinded Independent Central Review (BICR) Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] Up to approximately 6 years
Secondary Outcome -All Cohorts: Duration of Response (DOR) as Assessed by the Investigator Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] -Cohorts A, B, D, F, G: PFS as Assessed by the Investigator Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] -Cohorts A-F: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] -Cohorts A-F: PFS as Assessed by IRF Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] -Cohorts A-F: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ] -All Cohorts: Overall Survival (OS) [ Time Frame: Baseline up to approximately 6 years ] -All Cohorts: Percentage of Participants with Adverse Events (AEs) [ Time Frame: Baseline up to approximately 6 years ] Up to approximately 6 years
Secondary Outcome -Cohorts A, B, D, E, F: Percentage of Participants with Improvement Compared with Baseline in Total Severity Symptom Score as Measured by Symptoms in Lung Cancer (SILC) Scale in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] -Cohorts A-F: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by the SILC Scale [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] -Cohorts C, E, F: Change from Baseline in Patient-Reported Lung Cancer Symptom (Cough, Dyspnea, Chest pain) Score as Measured by the SILC Scale [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] -Cohorts A-F: Change from Baseline in Health Related Quality of Life (HRQoL) Scores as Measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire - C30 (EORTC QLQ-C30) [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] -Cohorts A, B, D, E, F: Change from Baseline in HRQoL Scores as Measured by the SILC Scale [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] All Cohorts: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the EORTC QLQ-C30 [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] Baseline up to approximately 6 years
Secondary Outcome -Cohorts A, B, D, E, F: Change from Baseline in Patient Functioning and Symptoms Score as Measured by the SILC Scale [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] -All Cohorts: Health Status Assessed as an Index Score Using the European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) Questionnaire [ Time Frame: Baseline, every 4 weeks through Cycle 6 (1 Cycle = 21 or 28 days), every 8 weeks thereafter up to approximately 6 years ] -Cohorts E, F: Serum Concentration of Atezolizumab [ Time Frame: Pre-dose (0 hr), 1.5 and 4 hr post-dose on Day 1 of Cycles 1, 2, 3, 4 and 5; and pre-dose on Day 1 of each subsequent treatment cycle (1 cycle = 28 days) ] -Cohorts E, F: Change from Baseline in Anti-Drug Antibodies (ADAs) [ Time Frame: Baseline up to approximately 6 years ] -Cohorts E, F: Time to Confirmed Deterioration (TTCD) in Participant-Reported Lung Cancer Symptoms of Cough, Dyspnea, and Chest Pain, as Measured by the Symptoms in Lung Cancer (SILC) [ Time Frame: Baseline up to approximately 6 years ] -Cohorts E, F: Proportion of Participants who Improve Compared with Baseline in Participant-Reported Lung Cancer Symptoms of Cough, Dyspnea, and Chest Pain, as Measured by the SILC [ Time Frame: Baseline up to approximately 6 years ] -Cohort G: Objective Response Rate (ORR) as Assessed by the Investigator Based on RECIST v1.1 [ Time Frame: Baseline up to approximately 6 years ] -Cohort G: TTCD on the EORTC QLQ-C30 Physical Functioning and Role Functioning Scales [ Time Frame: Baseline up to approximately 6 years ] Baseline up to approximately 6 years
Secondary Outcome -Cohort G: Proportion of Participants Reporting Clinically Meaningful Deterioration in Fatigue, Chest Pain, Physical and Role Functioning as Measured by the EORTC QLQ-LC13 and QLQ-C30 Questionnaires [ Time Frame: Cycle 5 (1 cycle = 21 or 28 days) ] -Cohort G: Change from Baseline in Fatigue, Chest Pain, Physical and Role Functioning as Measured by the EORTC QLQ-LC13 and QLQ-C30 Questionnaires [ Time Frame: Cycle 5 (1 cycle = 21 or 28 days) ] -Cohort G: Tolerability of GDC-6036 or Docetaxel as Assessed by the Patient-Reported Outcomes Common Terminology Criteria for Adverse Events (PRO-CTCAE) [ Time Frame: Cycles 1-3 (1 cycle = 21 days) ] -Cohort G: Plasma Concentration of GDC-6036 [ Time Frame: Cycles 1-5 (1 cycle = 21 days) ] 21 or 28 days
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Aga Khan University Hospital Nairobi 3rd Parklands Avenue, Off Limuru Road Nairobi 00100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Hoffmann La Roche The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya Nairobi 00100 Kenya Commercial Sector/Industry
COLLABORATORS
Name Street address City Postal code Country
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Saleh Mansoor mansoor.saleh@aku.edu +254709931500 Aga Khan University, Nairobi, 3rd Parklands Avenue, Nairobi-Kenya
City Postal code Country Position/Affiliation
Nairobi Kenya Professor of Hematology and Oncology
Role Name Email Phone Street address
Public Enquiries Tamara Talhouk tamara.talhouk@roche.com +254794650436 The Atrium, 6th Floor Chaka Road, off Lenana Road P.O. Box 44212-00100 Nairobi, Kenya
City Postal code Country Position/Affiliation
Nairobi Kenya Interim Clinical Operations Lead Clinical Operations Network Area Africa
Role Name Email Phone Street address
Scientific Enquiries Vijay Prasad vijay.prasad@roche.com +447557549324 Welwyn
City Postal code Country Position/Affiliation
Welwyn United Kingdom MEDICAL MONITOR
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes There is a plan to share IPD. Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Qualified researchers may request access to individual patient-level data through the clinical study data request platform (www.vivli.org). Further details on Roche's criteria for eligible studies are available here (https://vivli.org/ourmember/roche/). --For further details on Roche's Global Policy on the Sharing of Clinical Information and how to request access to related clinical study documents, see here (https://www.roche.com/research_and_development/who_we_are_how_we_work/clinical_trials/our_commitment_to_data_sharing.htm). Clinical Study Report,Informed Consent Form Roche commits to submit a manuscript to a peer-reviewed journal reporting primary clinical trials results no later than 18 months after the first product approval or decision to discontinue development of the product. Available studies are listed and available on the Vivli platform. Data requestors should use the Vivli data request form to request companies data Package(s). If approved requestors will need to sign a Data Use Agreement and the anonymized data will be shared in the Vivli secure research environment.
URL Results Available Results Summary Result Posting Date First Journal Publication Date
https://vivli.org/ourmember/roche/ No
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Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information