A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment

• Register: ClinicalTrials.gov
• Last refreshed on: 12 December 2020
• Main ID: NCT01801111
• Date of registration: 20/02/2013
• Prospective Registration: Yes
• Primary sponsor: Hoffmann-La Roche
• Public title: A Study of Alectinib (RO5424802) in Participants With Non-Small Cell Lung Cancer Who Have Anaplastic Lymphoma Kinase (ALK) Mutation and Failed Crizotinib Treatment
• Scientific title: An Open-Label, Non-Randomized, Multicenter Phase I/II Trial of RO5424802 Given Orally to Non-Small Cell Lung Cancer Patients Who Have ALK Mutation and Who Have Failed Crizotinib Treatment
• Date of first enrolment: June 20, 2013
• Target sample size: 138
• Recruitment status: Completed
• URL: https://clinicaltrials.gov/show/NCT01801111
• Study type: Interventional
• Study design: Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label).
• Phase: Phase 1/Phase 2

Countries of recruitment

Australia, Belgium, China, Denmark, France, Germany, Hong Kong, Italy, Korea, Republic of, Luxembourg, Netherlands, Russian Federation, Singapore, Spain, Sweden, Taiwan, United Kingdom, United States

Contacts

• Name: Clinical Trials
• Affiliation: Hoffmann-La Roche

Key inclusion & exclusion criteria

Inclusion Criteria:

- Locally advanced or metastatic non-small cell lung cancer (stage IIIB or IV by
American Joint Committee on Cancer [AJCC])

- Eastern Cooperative Oncology Group (ECOG) performance status 0-2

- Documented ALK rearrangement based on Food and Drug Administration (FDA)-approved test

- Prior treatment with crizotinib and progression according to response evaluation
criteria in solid tumors version 1.1 (RECIST v1.1) criteria. Participants had to have
a minimum 1-week wash-out period between the last dose of crizotinib and the first
dose of study treatment. Participants can either be chemotherapy-naïve or have
received at least one line of platinum-based chemotherapy

- Adequate hematologic, hepatic, and renal function

- Participants with brain or leptomeningeal metastases are allowed if protocol defined
criteria are met

- Measurable disease according to RECIST v1.1 prior to administration of first dose of
study drug

Exclusion Criteria:

- Receipt of any other ALK inhibitors in addition to crizotinib

- Receipt of any prior cytotoxic chemotherapy for ALK-positive NSCLC within 4 weeks
prior to the first dose of study drug

- Participants who received crizotinib or any other tyrosine kinase inhibitors need to
have a minimum 1-week washout period before the first dose of study drug

- Active or uncontrolled infectious diseases requiring treatment

- National Cancer Institute Common Terminology Criteria for Adverse Events version 4.03
(NCI CTCAE v4.03) Grade 3 or higher toxicities due to prior therapy that have not
shown improvement and are considered to interfere with current study medication

- History of organ transplant

- Co-administration of anti-cancer therapies other than those administered in this study

- Baseline corrected Q-T interval (QTc) greater than (>) 470 milliseconds, or baseline
symptomatic bradycardia (less than 45 heart beats per minute)

- Pregnant or breastfeeding women

- Known Human Immunodeficiency Virus (HIV) positivity or Acquired Immunodeficiency
Syndrome (AIDS)-related illness

- History of hypersensitivity to any of the additives in the alectinib formulation

- Any clinically significant concomitant disease or condition that could interfere with,
or for which treatment might interfere with, the conduct of the study, or absorption
of oral medications, or that would, in the opinion of the principal investigator, pose
an unacceptable risk to the participant in the study



Age minimum: 18 Years
Age maximum: N/A
Gender: All

Health Condition(s) or Problem(s) studied

Non-Small-Cell Lung Carcinoma

Intervention(s)

Drug: Alectinib

Drug: Erlotinib

Primary Outcome(s)

Percentage of Participants With Dose Limiting Toxicities (DLTs) [Time Frame: Cycle 1 (up to 28 days)]

Recommended Phase 2 Dose (RP2D) of Alectinib [Time Frame: Cycle 1 (up to 28 days)]

Percentage of Participants Achieving Objective Response (Complete Response [CR] or Partial Response [PR]) as Assessed by Independent Radiological Review Committee (IRC) in Response Evaluable (RE) Population [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Pretreated Participants [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Secondary Outcome(s)

Cmax of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Area Under the Plasma Concentration-Time Curve From Time 0 to 10 Hours Post-dose (AUC[0-10]) of Alectinib [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Percentage of Participants Achieving CR, PR or Stable Disease (SD) According to RECIST v1.1 in RE Population [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Duration of Response (DoR) as Assessed by IRC in RE Population [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Time to Last Measurable Plasma Concentration (Tlast) of Alectinib [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Metabolite to Parent Ratio Based on AUC(0-last) [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Percentage of Participants Achieving CNS Objective Response as Assessed by IRC According to Radiology Assessment in Neuro-Oncology (RANO) Criteria [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)]

CNS Duration of Response (CDoR) as Assessed by IRC According to RECIST v1.1 [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Pretreated Participants [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in RE Population [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

AUC(0-last) of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Ctrough of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs) on Day 21 of Cycle 1]

Peak to Trough Ratio of Alectinib [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 21 of Cycle 1]

Accumulation Ratio of Alectinib [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1]

Area Under the Plasma Concentration-Time Curve From Time 0 to Tlast (AUC[0-last]) of Alectinib [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Accumulation Ratio of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hours post-dose on Day 1 and Day 21 of Cycle 1]

AUC(0-10) of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Percentage of Participants Who Died of Any Cause [Time Frame: Baseline up to death from any cause (up to approximately 4 years)]

Metabolite to Parent Ratio Based on AUC(0-10) [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Time to Cmax (Tmax) of Alectinib [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Percentage of Participants Achieving Central Nervous System (CNS) Objective Response as Assessed by IRC According to RECIST v1.1 [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

CDoR as Assessed by IRC According to RANO Criteria [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)]

Tmax of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by Investigator in Chemotherapy-Naive Participants [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Maximum Observed Plasma Concentration (Cmax) of Alectinib [Time Frame: Pre-dose (0 hours [hrs]), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Percentage of Participants Achieving Objective Response (CR or PR) as Assessed by IRC in Chemotherapy-Naive Participants [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Progression Free Survival (PFS) as Assessed by IRC in Safety Population [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Percentage of Participants With CNS Progression as Assessed by IRC According to RECIST v 1.1 [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator; then survival follow-up until cutoff 18 August 2014 (up to approximately 53 weeks)]

Tlast of Alectinib Metabolite [Time Frame: Pre-dose (0 hrs), and 0.5, 1, 2, 4, 6, 8, 10, 12 hrs post-dose on Day 1 and Day 21 of Cycle 1]

Trough Plasma Concentration (Ctrough) of Alectinib [Time Frame: Pre-dose (0 hrs) on Day 21 of Cycle 1]

Overall Survival (OS) [Time Frame: Baseline up to death from any cause (up to approximately 4 years)]

Percentage of Participants With PD as Assessed by IRC According to RECIST v1.1 or Death From Any Cause in Safety Population [Time Frame: Baseline; assessments every 8 weeks post-baseline until progressive disease, unacceptable toxicity, consent withdrawal, death, other reason deemed by investigator, or last tumor assessment (up to approximately 2.5 years)]

Secondary ID(s)

2012-004455-36

NP28673

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Results

• Results available: Yes
• Date Posted: 26/05/2016
• URL: https://clinicaltrials.gov/ct2/show/results/NCT01801111