We offer treatment search services for the latest developments in treatment of any illness including regular weekly treatment updates. Learn more about our treatment search services.
//////////////////////////////////////////////////////////////////////////////////////////////////////////////////
New Clinical Trial for Nonsmall Cell Lung Cancer
This clinical trial for nonsmall cell lung cancer was announced on June 8, 2017. It is expected to begin recruiting patients soon.
Our TWU service checks weekly for new clinical trials and treatment reports that may be helpful to our clients in finding the best treatment for their particular illness.
A Study to Evaluate Efficacy and Safety of Multiple Targeted Therapies as Treatments for Participants With Non-Small Cell Lung Cancer (NSCLC) (B-FAST)
- Full Text View
- Tabular View
- No Study Results Posted
- Disclaimer
- How to Read a Study Record
Purpose
| Condition | Intervention | Phase |
|---|---|---|
| Non-Small Cell Lung Cancer | Drug: Alectinib Drug: Atezolizumab Drug: Pemetrexed Drug: Cisplatin Drug: Carboplatin Drug: Gemcitabine |
Phase 2 Phase 3 |
| Study Type: | Interventional |
| Study Design: | Allocation: Randomized Intervention Model: Parallel Assignment Masking: No masking 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) |
Primary Outcome Measures:
- 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) ]
- 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) ]
- 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) ]
Secondary Outcome Measures:
- 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) ]
- Cohorts A and B: 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) ]
- Cohorts A and B: 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) ]
- 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) ]
- Cohorts A and B: 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) ]
- 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) ]
- 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) ]
- All Cohorts: Overall Survival [ Time Frame: Baseline up to approximately 6 years ]
- All Cohorts: Percentage of Participants with Adverse Events [ Time Frame: Baseline up to approximately 6 years ]
- Cohorts A and B: 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 ]
- 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 ]
- 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 ]
- 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 ]
- Cohorts A and B: 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 ]
- Cohorts A and B: 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 ]
- Cohort B: Percentage of Participants with Dose-Limiting Toxicities (DLTs) [ Time Frame: Day 1 to Day 28 of Cycle 1 (cycle length = 28 days) ]
- Cohort B: Maximum Plasma Concentration (Cmax) of Alectinib [ Time Frame: DFP: pre-dose (0 hour [hr]) on Days 1, 8 of Cycle 1 and Day 1 of Cycles 2, 3, 4; 0.5 hours (hr), 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days); DEP: pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (1 Cycle=28 days) ]
DFP: Dose-Finding Phase; DEP: Dose-Expanding Phase.
- 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 Days 1, 8 of Cycle 1 and Day 1 of Cycles 2, 3, 4; 0.5 hours (hr), 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days); DEP: pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (1 Cycle=28 days) ]
- Cohort B: Time to Reach Cmax (Tmax) of Alectinib [ Time Frame: DFP: pre-dose (0 hr) on Days 1, 8 of Cycle 1 and Day 1 of Cycles 2, 3, 4; 0.5 hours (hr), 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days); DEP: pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (1 Cycle=28 days) ]
- Cohort B: Half-Life (t1/2) of Alectinib [ Time Frame: DFP: pre-dose (0 hr) on Days 1, 8 of Cycle 1 and Day 1 of Cycles 2, 3, 4; 0.5 hours (hr), 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days); DEP: pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (1 Cycle=28 days) ]
- Cohort B: Metabolite to Parent Exposure Ratio for AUC0-last [ Time Frame: DFP: pre-dose (0 hr) on Days 1, 8 of Cycle 1 and Day 1 of Cycles 2, 3, 4; 0.5 hours (hr), 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days); DEP: pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (1 Cycle=28 days) ]
- Cohort B: Metabolite to Parent Exposure Ratio for Cmax [ Time Frame: DFP: pre-dose (0 hr) on Days 1, 8 of Cycle 1 and Day 1 of Cycles 2, 3, 4; 0.5 hours (hr), 1, 2, 4, 6, 8 and 10 hr post-dose on Day 1 of Cycle 2 (1 Cycle=28 days); DEP: pre-dose (0 hr) on Day 1 of Cycles 1, 2, 3, 4 (1 Cycle=28 days) ]
- 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) ]
- 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 ]
| Estimated Enrollment: | 580 |
| Anticipated Study Start Date: | September 3, 2017 |
| Estimated Study Completion Date: | December 31, 2021 |
| Estimated Primary Completion Date: | March 3, 2020 (Final data collection date for primary outcome measure) |
| Arms | Assigned Interventions |
|---|---|
| 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, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death.
|
Drug: Alectinib
Participants will receive 600, 900, 1200 mg or RP2D orally BID 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, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death if the recommended phase 2 dose (RP2D) is not established in any other clinical study.
|
Drug: Alectinib
Participants will receive 600, 900, 1200 mg or RP2D orally BID 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, loss of clinical benefit, unacceptable toxicity, withdrawal of consent or death.
|
Drug: Alectinib
Participants will receive 600, 900, 1200 mg or RP2D orally BID 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).
|
Eligibility
| Ages Eligible for Study: | 18 Years and older (Adult, Senior) |
| Sexes Eligible for Study: | All |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- 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
- Active or untreated CNS metastases as determined by computed tomography (CT) or magnetic resonance imaging (MRI) evaluation during screening and prior radiographic assessments
- History of other malignancy within 5 years prior to screening, except for appropriately treated carcinoma in situ of the cervix, non-melanoma skin carcinoma, in situ ductal adenocarcinoma of the breast, in situ prostate cancer, limited stage bladder cancer, Stage I uterine cancer, or other cancers from which the patient has been disease-free for at least 2 years
- 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
Contacts and Locations
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, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT03178552
| 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 62 Study Locations More Information
| Responsible Party: | Hoffmann-La Roche |
| ClinicalTrials.gov Identifier: | NCT03178552 History of Changes |
| Other Study ID Numbers: | BO29554 2017-000076-28 ( EudraCT Number ) |
| Study First Received: | June 5, 2017 |
| Last Updated: | June 5, 2017 |
| Individual Participant Data | |
| 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 Bronchial Neoplasms Respiratory Tract Diseases Carcinoma, Bronchogenic Gemcitabine Cisplatin Carboplatin Pemetrexed |
New PreMedline Report for Nonsmall Cell Lung Cancer
This study was made available on April 28 in the PreMedline Database. Studies are entered in the PreMedline Database from a few weeks to several months prior to being indexed and moved to the PubMed (Medline) Database.
Our TWU service checks the PreMedline Database weekly for new treatments that may be helpful to our clients in finding the best treatment for their particular illness.
Functional lung avoidance and response-adaptive escalation (FLARE) RT: Multimodality plan dosimetry of a precision radiation oncology strategy.
Abstract
PURPOSE:
Nonsmall cell lung cancer (NSCLC) patient radiation therapy (RT) is planned without consideration of spatial heterogeneity in lung function or tumor response. We assessed the dosimetric and clinical feasibility of functional lung avoidance and response-adaptive escalation (FLARE) RT to reduce dose to [99m Tc]MAA-SPECT/CT perfused lung while redistributing an escalated boost dose within [18 F]FDG-PET/CT-defined biological target volumes (BTV).
METHODS:
Eight stage IIB-IIIB NSCLC patients underwent FDG-PET/CT and MAA-SPECT/CT treatment planning scans. Perfused lung objectives were derived from scatter/collimator/attenuation-corrected MAA-SPECT uptake relative to ITV-subtracted lung to maintain < 20 Gy mean lung dose (MLD). Prescriptions included 60 Gy to the planning target volume (PTV) and concomitant boost of 74 Gy mean to biological target volumes (BTV = GTV + PET gradient segmentation) scaled to each BTV voxel by relative FDG-PET SUV. Dose-painting-by-numbers prescriptions were integrated into commercial treatment planning systems via uptake threshold discretization. Dose constraints for lung, heart, cord, and esophagus were defined. FLARE RT plans were optimized with volumetric modulated arc therapy (VMAT), proton pencil beam scanning (PBS) with 3%-3 mm robust optimization, and combination of PBS (avoidance) plus VMAT (escalation). The high boost dose region was evaluated within a standardized SUVpeak structure. FLARE RT plans were compared to reference VMAT plans. Linear regression between radiation dose to BTV and normalized FDG PET SUV at every voxel was conducted, from which Pearson linear correlation coefficients and regression slopes were extracted. Spearman rank correlation coefficients were estimated between radiation dose to lung and normalized SPECT uptake. Dosimetric differences between treatment modalities were evaluated by Friedman nonparametric paired test with multiple sampling correction.
RESULTS:
No unacceptable violations of PTV and normal tissue objectives were observed in 24 FLARE RT plans. Compared to reference VMAT plans, FLARE VMAT plans achieved a higher mean dose to BTV (73.7 Gy 98195. 61.3 Gy), higher mean dose to SUVpeak (89.7 Gy vs. 60.8 Gy), and lower mean dose to highly perfused lung (7.3 Gy vs. 14.9 Gy). These dosimetric gains came at the expense of higher mean heart dose (9.4 Gy vs. 5.8 Gy) and higher maximum cord dose (50.1 Gy vs. 44.6 Gy) relative to the reference VMAT plans. Between FLARE plans, FLARE VMAT achieved higher dose to the SUVpeak ROI than FLARE PBS (89.7 Gy vs. 79.2 Gy, P = 0.01), while FLARE PBS delivered lower dose to lung than FLARE VMAT (11.9 Gy vs. 15.6 Gy, P < 0.001). Voxelwise linear dose redistribution slope between BTV dose and FDG PET uptake was higher in magnitude for FLARE PBS + VMAT (0.36 Gy per %SUVmax ) compared to FLARE VMAT (0.27 Gy per %SUVmax ) or FLARE PBS alone (0.17 Gy per %SUVmax ).
CONCLUSIONS:
FLARE RT is clinically feasible with VMAT and PBS. A combination of PBS for functional lung avoidance and VMAT for FDG PET dose escalation balanced target and normal tissue objective tradeoffs. These results provide a technical platform for testing of FLARE RT safety and efficacy within a precision radiation oncology trial.
END