ClinicalTrials.gov
ClinicalTrials.gov Menu

A Study to Evaluate Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (B-FAST)

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: NCT03178552
Recruitment Status : Recruiting
First Posted : June 7, 2017
Last Update Posted : November 8, 2018
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Non-Small Cell Lung Cancer Drug: Alectinib Drug: Atezolizumab Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin Drug: Gemcitabine Drug: Entrectinib Phase 2 Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 580 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official 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 (B-FAST: Blood-First Assay Screening Trial)
Actual Study Start Date : September 22, 2017
Estimated Primary Completion Date : February 13, 2020
Estimated Study Completion Date : January 2, 2022

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lung Cancer

Arm Intervention/treatment
Experimental: Cohort A: Alectinib 600 Milligrams (mg)

This cohort includes participants with anaplastic lymphoma kinase (ALK) positive NSCLC. Participants will receive alectinib 600 mg orally twice in a day (BID) until disease progression, unacceptable toxicity, withdrawal of consent or death.

Enrollment to Cohort A is complete.

Drug: Alectinib
Participants will receive 600 mg BID (Cohort A); 900, 1200, or 750 mg BID (Cohort B) or RP2D BID; orally until disease progression, unacceptable toxicity, withdrawal of consent or death.
Other Name: RO5424802

Experimental: Cohort B: Dose Finding Phase (DFP) Alectinib

This cohort includes participants with rearranged during transfection (RET) positive NSCLC. Participants may receive alectinib 900 or 1200 mg orally BID until disease progression, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study. Participants may receive 750 mg or 600 mg, if it is unsafe to pursue the higher starting dose.

Enrollment to Cohort B is complete.

Drug: Alectinib
Participants will receive 600 mg BID (Cohort A); 900, 1200, or 750 mg BID (Cohort B) or RP2D BID; orally until disease progression, unacceptable toxicity, withdrawal of consent or death.
Other Name: RO5424802

Experimental: Cohort B: Dose Expansion Phase (DEP) Alectinib

This cohort includes participants with RET positive NSCLC. Participants will receive alectinib at the RP2D established in the DFP of Cohort B or a separate clinical study. Participants will continue receiving study treatment until disease progression, unacceptable toxicity, withdrawal of consent or death.

Enrollment to Cohort B is complete.

Drug: Alectinib
Participants will receive 600 mg BID (Cohort A); 900, 1200, or 750 mg BID (Cohort B) or RP2D BID; orally until disease progression, unacceptable toxicity, withdrawal of consent or death.
Other Name: RO5424802

Experimental: Cohort C: Atezolizumab 1200 mg
This cohort includes participants with bTMB positive NSCLC. Participants will receive atezolizumab at a dose of 1200 mg administered by IV infusion every 21 days (Q21D) until disease progression, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death.
Drug: Atezolizumab
Participants will receive atezolizumab 1200 mg IV infusion Q21D.
Other Name: RO5541267

Active Comparator: Cohort C: Pemetrexed, Cisplatin or Carboplatin
This cohort includes participants with bTMB positive, non-squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Carboplatin at a dose of area under the concentration-time curve (AUC) of 5 or 6 IV or cisplatin at a dose of 75 milligrams per meter square (mg/m^2) IV on Day 1 of each cycle combined with pemetrexed at a dose of 500 mg/m^2 IV on Day 1 of each cycle. Pemetrexed may be continued as maintenance therapy every 21 days (Q21D) as per local standard of care.
Drug: Pemetrexed
Participants will receive pemetrexed 500 mg/m^2 IV infusion on Day 1 Q21D.

Drug: Cisplatin
Participants will receive cisplatin 75 mg/m^2 IV on Day 1 Q21D.

Drug: Carboplatin
Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.

Active Comparator: Cohort C: Gemcitabine, Cisplatin or Carboplatin
This cohort includes participants with bTMB positive, squamous NSCLC. Participants will receive 4 or 6 cycles of treatment, with each cycle being 21 days in duration. Gemcitabine 1250 mg/m^2 IV on Days 1 and 8 of every cycle and cisplatin 75 mg/m^2 IV on Day 1 Q21D or gemcitabine 1000 mg/m^2 IV on Days 1 and 8 of every cycle and carboplatin AUC 5 IV on Day 1 Q21D.
Drug: Cisplatin
Participants will receive cisplatin 75 mg/m^2 IV on Day 1 Q21D.

Drug: Carboplatin
Participants will receive carboplatin of AUC 5 or 6 IV on Day 1 Q21D.

Drug: Gemcitabine
Participants will receive gemcitabine 1000 or 1250 mg/m^2 on Days 1 and 8 of every cycle (1 Cycle=21 days).

Experimental: Cohort D: Entrectinib 600 Milligrams (mg)
This cohort includes participants with c-ros oncogene 1 positive (ROS1+) NSCLC. Participants will receive entrectinib 600 mg orally once a day (QD) until disease progression, unacceptable toxicity, withdrawal of consent or death.
Drug: Entrectinib
Participants will receive entrectinib 600 mg orally QD.
Other Name: RO7102122




Primary Outcome Measures :
  1. Cohort A: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the Response Evaluation Criteria in Solid Tumors (RECIST) Version (v) 1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  2. Cohort B: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  3. Cohort C: Progression Free Survival (PFS) as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  4. Cohort D: Percentage of Participants with Confirmed Objective Response as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]

Secondary Outcome Measures :
  1. All Cohorts: Duration of Response as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  2. Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  3. Cohorts A, B and D: PFS as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  4. All Cohorts: Duration of Response as Assessed by the Independent Review Facility (IRF) Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  5. Cohorts A, B and D: Percentage of Participants with Clinical Benefit Response as Assessed by IRF Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  6. All Cohorts: PFS as Assessed by IRF Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  7. All Cohorts: Percentage of Participants with Confirmed Objective Response as Assessed by IRF Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  8. All Cohorts: Overall Survival [ Time Frame: Baseline up to approximately 6 years ]
  9. All Cohorts: Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 6 years ]
  10. Cohorts A, B and D: Percentage of Participants who Have Shown 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 ]
  11. All Cohorts: Time to Deterioration in Patient-Reported Lung Cancer Symptoms (Cough, Dyspnea and Chest Pain) as Measured by 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 ]
  12. Cohort C: 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 ]
  13. All Cohorts: 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 ]
  14. Cohorts A, B and D: 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 ]
  15. 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 ]
  16. Cohorts A, B and D: 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 ]
  17. 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 ]
  18. Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 28 of Cycle 1 (cycle length = 28 days) ]
  19. Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib [ Time Frame: DFP: pre-dose (0 hours [hr]) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) ]
    DFP: Dose-Finding Phase; DEP: Dose-Expanding Phase.

  20. Cohort B: Area Under the Concentration-Time Curve from Time Zero to the Last Measurable Concentration (AUC0-last) of Alectinib [ Time Frame: DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) ]
  21. Cohort B: Time to Reach Cmax (Tmax) of Alectinib [ Time Frame: DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) ]
  22. Cohort B: Half-Life (t1/2) of Alectinib [ Time Frame: DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) ]
  23. Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last [ Time Frame: DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) ]
  24. Cohort B: Metabolite to Parent Exposure Ratio for Cmax [ Time Frame: DFP: pre-dose (0 hr) on Day 1 of Cycle 2; 0.5, 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days) ]
  25. Cohort C: Percentage of Participants with Objective Response as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  26. Cohort C: Percentage of Participants Free from Disease Progression as Assessed by the Investigator Based on the RECIST v1.1 at Months 6 and 12 [ Time Frame: Months 6, 12 ]
  27. Cohort D: Time to CNS progression as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to CNS progression (up to approximately 6 years) ]
  28. Cohort D: Time to CNS progression as Assessed by the IRF Based on the RECIST v1.1 [ Time Frame: Baseline up to CNS progression (up to approximately 6 years) ]
  29. Cohort D: Intracranial Tumor Response Rate as Assessed by the Investigator Based on the RECIST v1.1 [ Time Frame: Baseline up to disease progression or death (up to approximately 6 years) ]
  30. Cohorts D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-C30 [ Time Frame: Baseline, every 4 weeks until disease progression, up to approximately 6 years ]
  31. Cohorts D: Percentage of Participants who have shown improvement compared with Baseline in patient-reported cognitive function, fatigue, HRQoL, headache and vision disorder per the EORTC QLQ-BN20 [ Time Frame: Baseline, every 4 weeks until disease progression, up to approximately 6 years ]
  32. Cohort D: Mean Plasma Concentration of Entrectinib [ 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). ]
  33. Cohort D: Mean Plasma Concentration of Entrectinib Metabolite M5 [ 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). ]


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.


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

Inclusion Criteria:

  • No prior systemic treatment for unresectable stage IIIB or IV NSCLC
  • 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

Exclusion Criteria:

  • Inability to swallow oral medication
  • Women who are pregnant or lactating
  • Symptomatic, untreated CNS metastases
  • History of malignancy other than NSLCL 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

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): NCT03178552


Contacts
Contact: Reference Study ID Number: BO29554 www.roche.com/about_roche/roche_worldwide.htm 888-662-6728 (U.S. and Canada) global-roche-genentech-trials@gene.com

  Show 168 Study Locations
Sponsors and Collaborators
Hoffmann-La Roche

Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT03178552     History of Changes
Other Study ID Numbers: BO29554
2017-000076-28 ( EudraCT Number )
First Posted: June 7, 2017    Key Record Dates
Last Update Posted: November 8, 2018
Last Verified: November 2018
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: Undecided

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Additional relevant MeSH terms:
Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Gemcitabine
Atezolizumab
Cisplatin
Carboplatin
Pemetrexed
Antibodies, Monoclonal
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antiviral Agents
Anti-Infective Agents
Enzyme Inhibitors
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Folic Acid Antagonists
Nucleic Acid Synthesis Inhibitors