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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT03600883




Registration number
NCT03600883
Ethics application status
Date submitted
26/06/2018
Date registered
26/07/2018

Titles & IDs
Public title
A Phase 1/2, Study Evaluating the Safety, Tolerability, PK, and Efficacy of Sotorasib (AMG 510) in Subjects With Solid Tumors With a Specific KRAS Mutation (CodeBreaK 100)
Scientific title
A Phase 1/2, Open-label Study Evaluating the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics, and Efficacy of Sotorasib (AMG 510) Monotherapy in Subjects With Advanced Solid Tumors With KRAS p.G12C Mutation and Sotorasib (AMG 510) Combination Therapy in Subjects With Advanced NSCLC With KRAS p.G12C Mutation (CodeBreaK 100)
Secondary ID [1] 0 0
20170543
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
KRAS p.G12C Mutant Advanced Solid Tumors 0 0
Condition category
Condition code

Intervention/exposure
Study type
Interventional(has expanded access)
Description of intervention(s) / exposure
Treatment: Drugs - sotorasib
Treatment: Drugs - Anti PD-1/L1
Treatment: Drugs - Midazolam

Experimental: Phase 1 Dose Exploration Part 1 monotherapy - Cohorts with food effect and alternative dosing regimens

Enrollment into the dose exploration cohorts may be from any eligible solid tumor type. Dose escalation will begin with 2-4 subjects treated at the lowest planned dose level of 180 mg. If no DLT is observed, dose escalation will continue to the next planned dose cohort

Experimental: Phase 1 Dose Expansion Part 2 monotherapy - Upon completing the dose exploration part of the study, dose expansion may proceed with 3 groups consisting of subjects with KRAS p.G12C mutant advanced solid tumors. Dose expansion in these 3 groups may be done concurrently

Experimental: Phase 1 combination arm with sotorasib and anti PD-1/L1 - Additional subjects will be enrolled into the combination arm with sotorasib in combination with an anti (PD-1/L1)

Experimental: Phase 1 monotherapy treatment naive advanced NSCLC - Separate cohort of part 1 dose expansion subjects to evaluate the safety and clinical activity of sotorasib administered orally once daily in subjects with previously untreated advanced non-small cell lung cancer (NSCLC). Drug-drug interaction will be evaluated in 6 of the subjects enrolled in the treatment naive cohort by adding Midazolam alone on Day -1 and in combination with sotorasib on Day 15 of Cycle 1, where each cycle is 21 days.

Experimental: Phase 2 monotherapy dose comparison - Subjects with NSCLC will be enrolled in a dose comparison study evaluating safety and efficacy

Experimental: Phase 1 Does escalation and Expansion monotherapy BID - BID 2L+solid tumors (fed state)


Treatment: Drugs: sotorasib
Characterize the pharmacokinetics (PK) of sotorasib following administration as an oral Tablet formulation

Treatment: Drugs: Anti PD-1/L1
Administered as an intravenous (IV) infusion

Treatment: Drugs: Midazolam
Administered as an oral hydrochloride (HCI) syrup

Intervention code [1] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Primary: Number of subjects with treatment-emergent adverse events
Timepoint [1] 0 0
24 Months
Primary outcome [2] 0 0
Primary: Number of subjects with treatment-related adverse events
Timepoint [2] 0 0
24 Months
Primary outcome [3] 0 0
Primary: Number of subjects with grade =3 treatment-emergent adverse events
Timepoint [3] 0 0
24 Months
Primary outcome [4] 0 0
Primary: Number of subjects with serious adverse events
Timepoint [4] 0 0
24 Months
Primary outcome [5] 0 0
Primary: Number of subjects with adverse events of interest
Timepoint [5] 0 0
24 Months
Primary outcome [6] 0 0
Primary: Number of subjects with clinically significant changes in vital signs
Timepoint [6] 0 0
Baseline to 24 Months
Primary outcome [7] 0 0
Primary: Number of subjects with clinically significant changes in physical examination results
Timepoint [7] 0 0
Baseline to 24 Months
Primary outcome [8] 0 0
Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)
Timepoint [8] 0 0
Baseline to 24 Months
Primary outcome [9] 0 0
Primary: Number of subjects with clinically significant changes in clinical laboratory values
Timepoint [9] 0 0
Baseline to 24 Months
Primary outcome [10] 0 0
Primary: Number of subjects with dose-limiting toxicities (DLTs)
Timepoint [10] 0 0
21 Days
Primary outcome [11] 0 0
Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
Timepoint [11] 0 0
24 Months
Primary outcome [12] 0 0
Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
Timepoint [12] 0 0
24 Months
Primary outcome [13] 0 0
Primary: Disease control as assessed by RECIST 1.1 criteria
Timepoint [13] 0 0
24 Months
Primary outcome [14] 0 0
Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
Timepoint [14] 0 0
24 Months
Primary outcome [15] 0 0
Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria
Timepoint [15] 0 0
24 Months
Secondary outcome [1] 0 0
Secondary: Plasma concentration (Cmax) of sotorasib
Timepoint [1] 0 0
15 Weeks
Secondary outcome [2] 0 0
Secondary: Plasma concentration (Cmax) of midazolam
Timepoint [2] 0 0
16 Days
Secondary outcome [3] 0 0
Secondary: Time to achieve Cmax (Tmax) of sotorasib
Timepoint [3] 0 0
15 Weeks
Secondary outcome [4] 0 0
Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib
Timepoint [4] 0 0
15 Weeks
Secondary outcome [5] 0 0
Secondary: Area under the plasma concentration-time curve (AUC) of midazolam
Timepoint [5] 0 0
16 Days
Secondary outcome [6] 0 0
Secondary: Clearance of midazolam from the plasma
Timepoint [6] 0 0
16 Days
Secondary outcome [7] 0 0
Secondary: Terminal half-life (t1/2) of midazolam
Timepoint [7] 0 0
16 Days
Secondary outcome [8] 0 0
Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
Timepoint [8] 0 0
24 Months
Secondary outcome [9] 0 0
Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
Timepoint [9] 0 0
24 Months
Secondary outcome [10] 0 0
Secondary: Disease control as assessed by RECIST 1.1 criteria
Timepoint [10] 0 0
24 Months
Secondary outcome [11] 0 0
Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
Timepoint [11] 0 0
24 Months
Secondary outcome [12] 0 0
Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
Timepoint [12] 0 0
24 Months
Secondary outcome [13] 0 0
Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria
Timepoint [13] 0 0
Baseline to 24 Months
Secondary outcome [14] 0 0
Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria
Timepoint [14] 0 0
24 Months
Secondary outcome [15] 0 0
Secondary: Overall survival (OS)
Timepoint [15] 0 0
24 Months
Secondary outcome [16] 0 0
Secondary: sotorasib exposure and QTc interval relationship
Timepoint [16] 0 0
24 Months
Secondary outcome [17] 0 0
Secondary: Progression-free survival (PFS) at 6 months
Timepoint [17] 0 0
6 Months
Secondary outcome [18] 0 0
Secondary: Progression-free survival (PFS) at 12 months
Timepoint [18] 0 0
12 Months
Secondary outcome [19] 0 0
Secondary: Overall survival (OS) at 12 months
Timepoint [19] 0 0
12 Months
Secondary outcome [20] 0 0
Secondary: Number of subjects with treatment-emergent adverse events
Timepoint [20] 0 0
24 Months
Secondary outcome [21] 0 0
Secondary: Number of subjects with grade =3 treatment-emergent adverse events
Timepoint [21] 0 0
24 Months
Secondary outcome [22] 0 0
Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30
Timepoint [22] 0 0
24 Months
Secondary outcome [23] 0 0
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by disease-specific modules Quality-of-Life Questionnaire Lung Cancer Module (QLQ LC13)
Timepoint [23] 0 0
24 Months
Secondary outcome [24] 0 0
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by non-small cell lung cancer symptom assessment questionnaire (NSCLC SAQ) for NSCLC
Timepoint [24] 0 0
24 Months
Secondary outcome [25] 0 0
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS)
Timepoint [25] 0 0
24 Months
Secondary outcome [26] 0 0
Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Change (PGIC) in cough, dyspnea and chest pain for NSCLC
Timepoint [26] 0 0
24 Months
Secondary outcome [27] 0 0
Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30
Timepoint [27] 0 0
24 Months
Secondary outcome [28] 0 0
Secondary: Treatment-related symptoms and impact on the subject as assessed by selected questions from the Patient-reported Outcome of the Common Terminology Criteria for Adverse Events (PRO-CTCAE library)
Timepoint [28] 0 0
24 Months
Secondary outcome [29] 0 0
Secondary: Treatment-related symptoms and impact on the subject as assessed by a single item about symptom bother, item GP5 of the Functional Assessment of Cancer Therapy - General (FACT-G)
Timepoint [29] 0 0
24 Months
Secondary outcome [30] 0 0
Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30
Timepoint [30] 0 0
Baseline to 24 Months

Eligibility
Key inclusion criteria
* Men or women greater than or equal to 18 years old.
* Pathologically documented, locally-advanced or metastatic malignancy with, KRAS p.G12C mutation identified through molecular testing.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion Criteria

* Active brain metastases from non-brain tumors.
* Myocardial infarction within 6 months of study day 1.
* Gastrointestinal (GI) tract disease causing the inability to take oral medication.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other
Other design features
Phase
Phase 1
Type of endpoint/s
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW,QLD,SA,VIC
Recruitment hospital [1] 0 0
Scientia Clinical Research Ltd - Randwick
Recruitment hospital [2] 0 0
Princess Alexandra Hospital - Woolloongabba
Recruitment hospital [3] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment hospital [4] 0 0
Peter MacCallum Cancer Centre - Parkville
Recruitment postcode(s) [1] 0 0
2031 - Randwick
Recruitment postcode(s) [2] 0 0
4102 - Woolloongabba
Recruitment postcode(s) [3] 0 0
5011 - Woodville South
Recruitment postcode(s) [4] 0 0
3050 - Parkville
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
Colorado
Country [3] 0 0
United States of America
State/province [3] 0 0
Connecticut
Country [4] 0 0
United States of America
State/province [4] 0 0
Delaware
Country [5] 0 0
United States of America
State/province [5] 0 0
Florida
Country [6] 0 0
United States of America
State/province [6] 0 0
Georgia
Country [7] 0 0
United States of America
State/province [7] 0 0
Indiana
Country [8] 0 0
United States of America
State/province [8] 0 0
Maryland
Country [9] 0 0
United States of America
State/province [9] 0 0
Massachusetts
Country [10] 0 0
United States of America
State/province [10] 0 0
Michigan
Country [11] 0 0
United States of America
State/province [11] 0 0
Missouri
Country [12] 0 0
United States of America
State/province [12] 0 0
New York
Country [13] 0 0
United States of America
State/province [13] 0 0
North Carolina
Country [14] 0 0
United States of America
State/province [14] 0 0
Ohio
Country [15] 0 0
United States of America
State/province [15] 0 0
Pennsylvania
Country [16] 0 0
United States of America
State/province [16] 0 0
South Carolina
Country [17] 0 0
United States of America
State/province [17] 0 0
Tennessee
Country [18] 0 0
United States of America
State/province [18] 0 0
Texas
Country [19] 0 0
United States of America
State/province [19] 0 0
Utah
Country [20] 0 0
United States of America
State/province [20] 0 0
Virginia
Country [21] 0 0
United States of America
State/province [21] 0 0
Washington
Country [22] 0 0
Austria
State/province [22] 0 0
Graz
Country [23] 0 0
Austria
State/province [23] 0 0
Innsbruck
Country [24] 0 0
Austria
State/province [24] 0 0
Krems
Country [25] 0 0
Austria
State/province [25] 0 0
Wien
Country [26] 0 0
Belgium
State/province [26] 0 0
Brussels
Country [27] 0 0
Belgium
State/province [27] 0 0
Charleroi
Country [28] 0 0
Belgium
State/province [28] 0 0
Edegem
Country [29] 0 0
Belgium
State/province [29] 0 0
Genk
Country [30] 0 0
Belgium
State/province [30] 0 0
Gent
Country [31] 0 0
Belgium
State/province [31] 0 0
Hasselt
Country [32] 0 0
Belgium
State/province [32] 0 0
Leuven
Country [33] 0 0
Belgium
State/province [33] 0 0
Liege
Country [34] 0 0
Belgium
State/province [34] 0 0
Roeselare
Country [35] 0 0
Brazil
State/province [35] 0 0
Rio Grande Do Sul
Country [36] 0 0
Brazil
State/province [36] 0 0
São Paulo
Country [37] 0 0
Brazil
State/province [37] 0 0
Rio de Janeiro
Country [38] 0 0
Canada
State/province [38] 0 0
Alberta
Country [39] 0 0
Canada
State/province [39] 0 0
Ontario
Country [40] 0 0
Canada
State/province [40] 0 0
Quebec
Country [41] 0 0
France
State/province [41] 0 0
Bordeaux
Country [42] 0 0
France
State/province [42] 0 0
Créteil
Country [43] 0 0
France
State/province [43] 0 0
Marseille cedex 5
Country [44] 0 0
France
State/province [44] 0 0
Paris
Country [45] 0 0
France
State/province [45] 0 0
Toulouse cedex 9
Country [46] 0 0
France
State/province [46] 0 0
Villejuif
Country [47] 0 0
Germany
State/province [47] 0 0
Essen
Country [48] 0 0
Germany
State/province [48] 0 0
Köln
Country [49] 0 0
Germany
State/province [49] 0 0
München
Country [50] 0 0
Greece
State/province [50] 0 0
Athens
Country [51] 0 0
Greece
State/province [51] 0 0
Heraklion - Crete
Country [52] 0 0
Greece
State/province [52] 0 0
Thessaloniki
Country [53] 0 0
Hungary
State/province [53] 0 0
Budapest
Country [54] 0 0
Hungary
State/province [54] 0 0
Kaposvar
Country [55] 0 0
Hungary
State/province [55] 0 0
Szekesfehervar
Country [56] 0 0
Hungary
State/province [56] 0 0
Tatabanya
Country [57] 0 0
Hungary
State/province [57] 0 0
Torokbalint
Country [58] 0 0
Japan
State/province [58] 0 0
Aichi
Country [59] 0 0
Japan
State/province [59] 0 0
Chiba
Country [60] 0 0
Japan
State/province [60] 0 0
Ehime
Country [61] 0 0
Japan
State/province [61] 0 0
Fukuoka
Country [62] 0 0
Japan
State/province [62] 0 0
Hokkaido
Country [63] 0 0
Japan
State/province [63] 0 0
Kanagawa
Country [64] 0 0
Japan
State/province [64] 0 0
Miyagi
Country [65] 0 0
Japan
State/province [65] 0 0
Niigata
Country [66] 0 0
Japan
State/province [66] 0 0
Okayama
Country [67] 0 0
Japan
State/province [67] 0 0
Osaka
Country [68] 0 0
Japan
State/province [68] 0 0
Shizuoka
Country [69] 0 0
Japan
State/province [69] 0 0
Tokyo
Country [70] 0 0
Japan
State/province [70] 0 0
Wakayama
Country [71] 0 0
Korea, Republic of
State/province [71] 0 0
Goyang-si Gyeonggi-do
Country [72] 0 0
Korea, Republic of
State/province [72] 0 0
Seongnam-si, Gyeonggi-do
Country [73] 0 0
Korea, Republic of
State/province [73] 0 0
Seoul
Country [74] 0 0
Portugal
State/province [74] 0 0
Lisboa
Country [75] 0 0
Portugal
State/province [75] 0 0
Matosinhos
Country [76] 0 0
Portugal
State/province [76] 0 0
Porto
Country [77] 0 0
Romania
State/province [77] 0 0
Bucuresti
Country [78] 0 0
Romania
State/province [78] 0 0
Cluj Napoca
Country [79] 0 0
Romania
State/province [79] 0 0
Craiova
Country [80] 0 0
Romania
State/province [80] 0 0
Iasi
Country [81] 0 0
Romania
State/province [81] 0 0
Ploiesti
Country [82] 0 0
Romania
State/province [82] 0 0
Timisoara
Country [83] 0 0
Spain
State/province [83] 0 0
Cataluña
Country [84] 0 0
Spain
State/province [84] 0 0
Comunidad Valenciana
Country [85] 0 0
Spain
State/province [85] 0 0
Madrid
Country [86] 0 0
Switzerland
State/province [86] 0 0
Basel
Country [87] 0 0
Switzerland
State/province [87] 0 0
Geneve
Country [88] 0 0
Switzerland
State/province [88] 0 0
Zurich

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
Amgen
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
MD
Address 0 0
Amgen
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request

Supporting document/s available: Study protocol, Statistical analysis plan (SAP), Informed consent form (ICF), Clinical study report (CSR)
When will data be available (start and end dates)?
Data sharing requests relating to this study will be considered beginning 18 months after the study has ended and either 1) the product and indication have been granted marketing authorization in both the US and Europe or 2) clinical development for the product and/or indication discontinues and the data will not be submitted to regulatory authorities. There is no end date for eligibility to submit a data sharing request for this study.
Available to whom?
Qualified researchers may submit a request containing the research objectives, the Amgen product(s) and Amgen study/studies in scope, endpoints/outcomes of interest, statistical analysis plan, data requirements, publication plan, and qualifications of the researcher(s). In general, Amgen does not grant external requests for individual patient data for the purpose of re-evaluating safety and efficacy issues already addressed in the product labelling. Requests are reviewed by a committee of internal advisors. If not approved, a Data Sharing Independent Review Panel will arbitrate and make the final decision. Upon approval, information necessary to address the research question will be provided under the terms of a data sharing agreement. This may include anonymized individual patient data and/or available supporting documents, containing fragments of analysis code where provided in analysis specifications. Further details are available at the URL below.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://www.amgen.com/datasharing


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.