Phase 2
N=47
A Study of Alectinib (CH5424802/RO5424802) in Participants With Anaplastic Lymphoma Kinase (ALK)-Rearranged Non-Small Cell Lung Cancer (NSCLC)
Non-Small Cell Lung Cancer
Bottom Line
View on ClinicalTrials.gov: NCT01871805 ↗Enrolled (actual)
47
Serious AEs
23.1%
Results posted
Feb 2016
Primary outcome: Primary: Number of Participants With Dose Limiting Toxicities (DLTs): Phase I — 0; 0; 0; 0 participants
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 2
- Interventions
- Alectinib (Drug)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hoffmann-La Roche
- Primary completion
- Oct 2014
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Number of Participants With Dose Limiting Toxicities (DLTs): Phase I |
0; 0; 0; 0; 2 | — |
| PRIMARY Recommended Phase II Dose (RP2D): Phase I |
600 | — |
| PRIMARY Percentage of Participants With Objective Response According to Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST v1.1) by Independent Review Committee (IRC): Phase II |
52.2 | 0.0056 sig |
| SECONDARY Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I |
69.2; 55.9 | 0.0251 sig |
| SECONDARY Duration of Response (DOR) According to RECIST v1.1 by Investigator: Phase I |
12.2; 11.0 | — |
| SECONDARY Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II |
52.9 | 0.0010 sig |
| SECONDARY Percentage of Participants With Disease Control According to RECIST v1.1 by Investigator: Phase II |
66.7 | — |
| SECONDARY Percentage of Participants With Disease Progression According to RECIST v1.1 by IRC or Death : Phase II |
66.7 | — |
| SECONDARY Progression-Free Survival (PFS) According to RECIST v1.1 by IRC: Phase II |
8.2 | — |
| SECONDARY Percentage of Participants With Disease Progression According to RECIST v1.1 by Investigator or Death : Phase II |
70.1 | — |
| SECONDARY PFS According to RECIST v1.1 by Investigator: Phase II |
8.4 | — |
| SECONDARY Percentage of Participants Who Died Due to Any Cause: Phase II |
51.7 | — |
| SECONDARY Overall Survival (OS) Time: Phase II |
27.9 | — |
| SECONDARY DOR According to RECIST v1.1 by IRC: Phase II |
14.9 | — |
| SECONDARY DOR According to RECIST v1.1 by Investigator: Phase II |
13.3 | — |
| SECONDARY Percentage of Participants With Central Nervous System Objective Response (COR) According to RECIST v1.1 by IRC: Phase II |
75.0 | — |
| SECONDARY Percentage of Participants With COR According to Response Assessment in Neuro-Oncology (RANO) Criteria by IRC: Phase II |
54.5 | — |
| SECONDARY CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II |
11.1 | — |
| SECONDARY CDOR According to RANO Criteria by IRC: Phase II |
12.1 | — |
| SECONDARY Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II |
— | — |
| SECONDARY Percentage of Participants With CNS Progression According to RANO Criteria by IRC: Phase II |
— | — |
| SECONDARY Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I |
73.5; 87.7; 45.3; 142.00; 158.0; 186.0 | — |
| SECONDARY Cmax After Multiple Dose of Alectinib: Phase I |
259; 618; 765; 670; 733; 1140 | — |
| SECONDARY Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I |
1360; 858; 1030; 3280; 3310; 3190 | — |
| SECONDARY AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I |
1800; 4510; 5970; 5300; 5780; 9800 | — |
| SECONDARY Ctrough After Multiple Dose of Alectinib: Phase II |
473; 521; 538; 538 | — |
| SECONDARY Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II |
53.59; 15.89; 0.00; 18.83; 0.00; 15.65 | — |
| SECONDARY Change From Baseline in EORTC Quality of Life Questionnaire Lung Cancer 13 (EORTC QLQ-LC13): Phase II |
30.85; -8.24; 0.00; -7.64; 0.00; -11.35 | — |
Summary
This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of alectinib in participants with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of participants will receive escalating doses of alectinib orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose.
Eligibility Criteria
Inclusion Criteria
- Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic NSCLC
- ALK-rearrangement confirmed by the Food and Drug Administration (FDA) approved test
- NSCLC that has failed crizotinib treatment
- Measurable disease as defined by RECIST v1.1
- Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to (<=) 2
- Adequate hematologic, hepatic and renal function
Exclusion Criteria
- Prior therapy with ALK inhibitor other than crizotinib
- Brain or leptomeningeal metastases that are symptomatic and/or requiring treatment
- History of serious cardiac dysfunction
- History of or current active infection with hepatitis B, hepatitis C or human immunodeficiency virus (HIV)
- Clinically significant gastrointestinal abnormality that would affect absorption of the drug
- Pregnant or lactating women
Data sourced from ClinicalTrials.gov (NCT01871805). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.