Trial record 1 of 1 for:    NCT01871805
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A Study of CH5424802/RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
Hoffmann-La Roche
ClinicalTrials.gov Identifier:
NCT01871805
First received: May 28, 2013
Last updated: July 1, 2016
Last verified: July 2016
  Purpose
This non-randomized, open-label, multicenter study will evaluate the safety and efficacy of CH5424802/RO5424802 in patients with ALK-rearranged non-small cell lung cancer who failed crizotinib treatment. In Phase I, cohorts of patients will receive escalating doses of CH5424802/RO5424802 orally twice daily. In Phase II, patients who failed crizotinib treatment will receive the recommended phase II dose (600 mg) daily in two oral doses.

Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: RO5424802
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I/II Study of the ALK Inhibitor CH5424802/ RO5424802 in Patients With ALK-Rearranged Non-Small Cell Lung Cancer Previously Treated With Chemotherapy and Crizotinib

Resource links provided by NLM:


Further study details as provided by Hoffmann-La Roche:

Primary Outcome Measures:
  • Number of Participants With Dose Limiting Toxicities (DLTs) - Phase I [ Time Frame: Cycle 1 of Phase I (21 days) ] [ Designated as safety issue: Yes ]
    The DLTs were defined as any which included Grade 4 thrombocytopenia or Grade 3 thrombocytopenia with bleeding or Grade 4 neutropenia continuing for greater than equal to (>=) 7 consecutive days, non-hematological toxicity of Grade 3 or higher (excluding transient electrolyte abnormalities, diarrhea, nausea, and vomiting that recovers to Grade 2 or lower with appropriate treatment and participants having Grade 2 aspartate transaminase (AST) and/or alanine transaminase (ALT) at baseline must have Grade 3 AST/ALT for 7 days or Grade 4 AST/ALT to be considered a DLT), and adverse events (AEs) that required suspension of treatment for a total of >=7 days which the Investigator could not rule out as been related to alectinib.

  • 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 [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    The objective response rate assessed by IRC was defined as the proportion of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of complete response (CR) or partial response (PR) based on the RECIST 1.1 criteria. CR: disappearance of all target and non-target lesions (TLs) and normalization of tumor markers. Pathological lymph nodes must have short axis measures less than (<) 10 millimeter (mm). PR: at least a 30 percent (%) decrease in the sum of measures (longest diameter for tumor lesions and short axis measure for nodes) of TLs, taking as reference the baseline sum of diameters. CR and PR were to be confirmed by repeat assessments ≥4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% confidence interval (CI).


Secondary Outcome Measures:
  • Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase I [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 105; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    The objective response rate was defined as the proportion of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST v1.1 criteria. Refer "Outcome Measure 2" for the definition of CR and PR. Clopper-Pearson method was used to calculate 95% CI.

  • Duration of Response (DOR) Assessed by Investigator: Phase I [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 105; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression (according to RECIST 1.1) or death (whichever occurred first). Participants who did not progress or did not die after they had a CR were censored at date of their last tumor measurement. Progressive disease (PD): at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. DOR curves and the median time to the event was estimated using the methodology of Kaplan and Meier and Brookmeyer and Crowley method was used to calculate 95% CI.

  • Percentage of Participants With Objective Response According to RECIST v1.1 by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1 at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    The objective response rate was defined as the proportion of responders in the response evaluable population, where responders were defined as participants determined to have a best overall response of CR or PR based on the RECIST 1.1 criteria. Refer "Outcome Measure 2" for the definition of CR and PR. CR and PR were to be confirmed by repeat assessments ≥4 weeks after initial documentation. Clopper-Pearson method was used to calculate 95% CI.

  • Percentage of Participants With Disease Control by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    Disease control rate assessed according to RECIST 1.1 was defined as the percentage of participants with a best overall response of CR, PR, or stable disease (SD) lasting for at least 12 weeks, after the first dose of alectinib. SD: neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD taking as reference the smallest sum of diameters on study. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. 95% CI for rates were constructed using Clopper-Pearson method.

  • Progression-Free Survival (PFS) by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST 1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Percentage of Participants With Disease Progression or Death by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    Participants who have neither progressed according to RECIST 1.1 nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.

  • PFS by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    PFS was defined as the time between first dose of alectinib and date of first documented disease progression according to RECIST 1.1 or death, whichever occurred first. Participants who have neither progressed nor died at the time of the last clinical cut-off or who lost to follow-up were censored at the date of the last tumor assessment showing no progression of disease either during the study treatment or during follow-up. Participants with no post-baseline assessments were censored at the date of first dose. Progression of disease is defined as at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. PFS curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Overall Survival (OS) Time: Phase II [ Time Frame: Baseline up to death (any cause) (data cutoff 24 October 2014, maximum follow up 60 weeks) ] [ Designated as safety issue: No ]
    OS was defined as the time between date of first dose and date of death due to any cause. Participants without an event were censored at the date last known to be alive. Participants without any follow up information were censored at the date of first dose. OS curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • DOR Assessed by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression according to RECIST 1.1 or death (whichever occurred first). Participants who did not progress or did not die after they had a confirmed response were censored at the date of their last tumor measurement. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. DOR curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • DOR Assessed by Investigator: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    DOR was defined for responders (CR or PR) as the time from when response was first documented, to first documented disease progression according to RECIST 1.1 or death (whichever occurred first). Participants who did not progress or did not die after they had a confirmed response were censored at the date of their last tumor measurement. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. DOR curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Percentage of Participants With Central Nervous System Objective Response Rate (CORR) Among Participants With Measurable Central Nervous System Lesions at Baseline According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    CORR was defined as the proportion of participants who had a CR or PR of the baseline CNS lesions, based on RECIST v.1.1. CNS responses according to RECIST v1.1 did not have to be confirmed. Refer "Outcome Measure 2" for the definition of CR and PR. 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Percentage of Participants With COOR According to Response Assessment in Neuro-Oncology (RANO) by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    CORR was defined as the proportion of participants who had a CR or PR according to RANO criteria of the baseline CNS lesions. As per RANO criteria, CR was defined as disappearance of all enhancing measurable and non-measurable disease, and no new lesions along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and stable or improved non enhancing T2/FLAIR lesions; PR was defined as 50% or more decrease in sum of the products of the diameters (SPD) of measurable enhancing measurable lesions, no new lesion along with stable or clinically improved status, participants off corticosteroids (or on physiologic replacement doses only) and no progression of non-measurable disease (enhancing and non-enhancing T2/FLAIR lesions. Clopper and Pearson method was used to calculate 95% CI.

  • CNS Duration of Response (CDOR) According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    CDOR was defined for CNS responders as the time from the first observation of a CNS response of CR or PR until first observation of CNS progression or death from any cause. An analysis by IRC using RECIST v1.1 was performed. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions. Refer "Outcome Measure 2" for the definition of CR and PR. DOR curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • CDOR According to RANO by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    CDOR was defined as the time from the first observation of a CNS response of CR or PR according to RANO criteria until first observation of CNS progression or death from any cause. An analysis by RANO criteria was performed. Definitions of CR or PR as per RANO was included in description of Outcome Measure 15. As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease) and clear worsening of neurological status with respect to the previous timepoint. DOR curves and the median time to the event was estimated using the methodology of Kaplan and Meier and 95% CI for median was computed using the method of Brookmeyer and Crowley.

  • Percentage of Participants With CNS Progression According to RECIST v1.1 by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1, at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cut-off date 24 October 2014) ] [ Designated as safety issue: No ]
    CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RECIST 1.1. PD: at least 20% increase in the sum of diameters of target lesions compared to the smallest sum of diameters on-study and absolute increase of at least 5 mm, progression of existing non-target lesions, or presence of new lesions.

  • Percentage of Participants With CNS Progression According to RANO by IRC: Phase II [ Time Frame: Every 6 weeks from Cycle 1 Day 1 at Cycles 2, 4, and 6 between Days 14-21, and every 3 cycles thereafter (assessed up to Week 60; data cutoff date of 24 October 2014) ] [ Designated as safety issue: No ]
    CNS disease progression was defined as a new CNS lesion or progression of pre-existing CNS lesions according to RANO criteria . As per RANO criteria, progression was defined as 25% or more increase in SPD of measurable enhancing (measurable) compared to the best response after initiation of therapy or Screening; increase (significant) in non-enhancing T2/FLAIR lesions, not attributable to other non-tumor causes; any new lesions; and clinical deterioration (not attributable to other non-tumor causes and not due to steroid decrease).

  • Maximum Observed Plasma Concentration (Cmax) After Single Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 ] [ Designated as safety issue: No ]
    Cmax was expressed in nanograms per milliliter (ng/mL).

  • Cmax After Multiple Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Area Under the Plasma Concentration (AUC) Versus Time Curve Extrapolated to Infinity (AUCinf) After Single Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8, 10, 24, 32 and 48 hours post-dose on Cycle 1 Day -3 ] [ Designated as safety issue: No ]
    AUCinf = AUC from time zero (pre-dose) to extrapolated infinite time. It is obtained from AUC (0- t) plus AUC (t-inf). AUC is expressed in hour*ng/mL.

  • AUC From Time Zero to Last Measurable Concentration (AUClast) After Multiple Dose of Alectinib: Phase I [ Time Frame: Pre-dose (0 hour), 0.5, 1, 2, 4, 6, 8 and 10 hours post-dose on Cycle 2 Day 1 ] [ Designated as safety issue: No ]
  • Ctrough After Multiple Dose of Alectinib: Phase II [ Time Frame: Pre-dose (0 hour) on Day 1 of Cycles 2, Cycle 3, Cycle 4, Cycle 5 ] [ Designated as safety issue: No ]
  • Change From Baseline in European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ-C30): Phase II [ Time Frame: Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, last visit (Week 60; data cutoff date of 24 October 2014) ] [ Designated as safety issue: No ]
    EORTC QLQ-C30: included functional scales (physical, role, cognitive, emotional, and social), global health status, symptom scales (fatigue, pain, nausea/vomiting) and single items (dyspnoea, appetite loss, insomnia, constipation/diarrhea and financial difficulties). Most questions used 4-point scale (1 'Not at all' to 4 'Very much'; 2 questions used 7-point scale [1 'very poor' to 7 'Excellent']). Scores were averaged and transformed to lie between 0-100 scale; for each of the symptom scales, higher score=better level of functioning or greater degree of symptoms and lower score indicates lower level of that particular symptom.

  • Change From Baseline in EORTC QLQ-LC13: Phase II [ Time Frame: Baseline, Weeks 6, 9, 12, 15, 18, 21, 24, 27, 30, 33, 36, 42, 48, last visit (Week 60; data cutoff date of 24 October 2014) ] [ Designated as safety issue: No ]
    EORTC QLQ-LC13: consisted of 13 questions with one symptom scale for dyspnea of 3 items and 10 single items (cough, haemoptysis, sore mouth, dysphagia, peripheral neuropathy, alopecia, pain in chest, pain in arm/shoulder, other pain, pain medication). Questions used 4-point scale (1 'Not at all' to 4 'Very much'. Scores were averaged and transformed to 0-100 scale; higher score=better level of functioning or greater degree of symptoms.


Enrollment: 127
Study Start Date: September 2013
Estimated Study Completion Date: May 2017
Estimated Primary Completion Date: May 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Phase I: dose-escalation Drug: RO5424802
multiple escalating doses given orally twice daily
Other Name: CH5424802
Experimental: Phase II: RP2 dose Drug: RO5424802
Recommended Phase II dose (600 mg) given orally twice daily
Other Name: CH5424802

  Eligibility

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Adult patients, >/= 18 years of age
  • Histologically confirmed, locally advanced, not amenable to curative therapy, or metastatic non-small cell lung cancer (NSCLC)
  • ALK-rearrangement confirmed by FDA approved test
  • NSCLC that has failed crizotinib treatment
  • Measurable disease as defined by RECIST v1.1
  • Eastern Cooperative Oncology Group (ECOG) performance status </= 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 HIV
  • Clinically significant gastrointestinal abnormality that would affect absorption of the drug
  • Pregnant or lactating women
  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: NCT01871805

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Sponsors and Collaborators
Hoffmann-La Roche
Investigators
Study Director: Clinical Trials Hoffmann-La Roche
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Hoffmann-La Roche
ClinicalTrials.gov Identifier: NCT01871805     History of Changes
Other Study ID Numbers: NP28761 
Study First Received: May 28, 2013
Results First Received: January 14, 2016
Last Updated: July 1, 2016
Health Authority: United States: Food and Drug Administration

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

ClinicalTrials.gov processed this record on August 29, 2016