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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05198934




Registration number
NCT05198934
Ethics application status
Date submitted
6/01/2022
Date registered
20/01/2022

Titles & IDs
Public title
Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
Scientific title
A Phase 3 Multicenter, Randomized, Open-label, Active-controlled Study of Sotorasib and Panitumumab Versus Investigator's Choice (Trifluridine and Tipiracil, or Regorafenib) for the Treatment of Previously Treated Metastatic Colorectal Cancer Subjects With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
Secondary ID [1] 0 0
20190172
Universal Trial Number (UTN)
Trial acronym
CodeBreak300
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Colorectal Cancer (CRC) 0 0
Condition category
Condition code
Cancer 0 0 0 0
Bowel - Back passage (rectum) or large bowel (colon)
Cancer 0 0 0 0
Sarcoma (also see 'Bone') - soft tissue
Cancer 0 0 0 0
Bone

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Sotorasib
Treatment: Drugs - Panitumumab
Treatment: Drugs - Trifluridine and Tipiracil
Treatment: Drugs - Regorafenib

Experimental: Arm A: Sotorasib 960 mg QD + panitumumab -

Experimental: Arm B: Sotorasib 240 mg QD + panitumumab -

Active comparator: Arm C : Investigator's choice - Participants will be administered trifluridine and tipiracil, or regorafenib


Treatment: Drugs: Sotorasib
Sotorasib will be administered orally

Treatment: Drugs: Panitumumab
Panitumumab will be administered as intravenous (IV) infusion

Treatment: Drugs: Trifluridine and Tipiracil
Trifluridine and Tipiracil will be administered orally

Treatment: Drugs: Regorafenib
Regorafenib will be administered orally

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

Outcomes
Primary outcome [1] 0 0
Progression-free Survival (PFS)
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Approximately 3 years
Secondary outcome [2] 0 0
Objective Response Rate (ORR)
Timepoint [2] 0 0
Approximately 3 years
Secondary outcome [3] 0 0
Duration of Response (DOR)
Timepoint [3] 0 0
Approximately 3 years
Secondary outcome [4] 0 0
Time to Response (TTR)
Timepoint [4] 0 0
Approximately 3 years
Secondary outcome [5] 0 0
Disease Control Rate (DCR)
Timepoint [5] 0 0
Approximately 3 years
Secondary outcome [6] 0 0
Investigator Assessed ORR
Timepoint [6] 0 0
Approximately 3 years
Secondary outcome [7] 0 0
Investigator Assessed PFS
Timepoint [7] 0 0
Approximately 3 years
Secondary outcome [8] 0 0
Number of Participants with a Treatment-emergent Adverse Event (TEAE)
Timepoint [8] 0 0
Approximately 3 years
Secondary outcome [9] 0 0
Change from Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory (BFI)
Timepoint [9] 0 0
Baseline and Week 8
Secondary outcome [10] 0 0
Change from Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory (BPI)
Timepoint [10] 0 0
Baseline and Week 8
Secondary outcome [11] 0 0
Change from Baseline in Physical Functioning as Measured by the Physical Function Domain of the European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire-Core Questionnaire (EORTC QLQ-C30)
Timepoint [11] 0 0
Baseline and Week 8
Secondary outcome [12] 0 0
Change from Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30
Timepoint [12] 0 0
Baseline and Week 8
Secondary outcome [13] 0 0
Change from Baseline For All Subscales of the BFI
Timepoint [13] 0 0
Baseline and Week 8
Secondary outcome [14] 0 0
Change from Baseline For All Subscales of the BPI
Timepoint [14] 0 0
Baseline and Week 8
Secondary outcome [15] 0 0
Change from Baseline For All Subscales and Domains of EORTC QLQ-C30
Timepoint [15] 0 0
Baseline and Week 8
Secondary outcome [16] 0 0
Change from Baseline in Visual Analog Scale (VAS) Scores as Measured by EuroQol-5D level 5 (EQ-5D-5L)
Timepoint [16] 0 0
Baseline and Week 8
Secondary outcome [17] 0 0
Average Score on Single Question on Symptom Bother GP5 from Functional Assessment of Cancer Therapy - General (FACT-G)
Timepoint [17] 0 0
Approximately 2 years
Secondary outcome [18] 0 0
Average Score of Patient Global Impression of Change (PGIC)
Timepoint [18] 0 0
Approximately 2 years
Secondary outcome [19] 0 0
Maximum Plasma Concentration (Cmax) of Sotorasib
Timepoint [19] 0 0
Day 1 to approximately 2 years
Secondary outcome [20] 0 0
Cmax of Panitumumab
Timepoint [20] 0 0
Day 1 to approximately 2 years
Secondary outcome [21] 0 0
Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib
Timepoint [21] 0 0
Day 1 to approximately 2 years
Secondary outcome [22] 0 0
AUC of Panitumumab
Timepoint [22] 0 0
Day 1 to approximately 2 years

Eligibility
Key inclusion criteria
* Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
* Age =18 years.
* Pathologically documented metastatic colorectal adenocarcinoma with Kirsten rat sarcoma (KRAS) p.G12C mutation as determined by prospective central testing, using the analytically validated Qiagen Therascreen KRAS RGQ polymerase chain reaction Kit in CRC as an investigational device demonstrating a KRAS p.G12C mutation is present. Local testing and documentation of KRAS p.G12C mutation should have been previously performed as part of standard of care.
* Participants will have received at least 1 prior line of therapy for metastatic disease. Participants must have received and progressed or experienced disease recurrence on or after fluoropyrimidine, irinotecan, and oxaliplatin given for metastatic disease unless the participant, in the opinion of the investigator, is not a candidate for fluoropyrimidine, irinotecan, or oxaliplatin, in which case, the participant may be eligible after investigator discussion with Amgen medical monitor provided participant has received at least one prior line of therapy for metastatic disease and provided trifluridine and tipiracil or regorafenib is deemed the appropriate next line of therapy for the participant.
* Measurable disease per Response Evaluation Criteria In Solid Tumors (RECIST) 1.1 criteria. Lesions previously radiated are not considered measurable unless they have progressed after radiation.
* Eastern Cooperative Oncology Group (ECOG) Performance Status of =2.
* Life expectancy of >3 months, in the opinion of the investigator.
* Adequate hematologic and end-organ function, defined as the following within 2 weeks prior to cycle 1 day 1:

* Absolute neutrophil count (ANC) =1.5 x 10^9/L (without granulocyte colony stimulating factor support within 2 weeks of laboratory test used to determine eligibility).
* Hemoglobin =9.0 g/dL (without transfusion within 2 weeks of laboratory test used to determine eligibility).
* Platelet count =100 x 10^9/L (without transfusion within 2 weeks of laboratory test used to determine eligibility).
* Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) =2.5 times the upper limit of normal (ULN).
* Serum bilirubin =1.0 x ULN. For participants with Gilbert's disease, total bilirubin or direct bilirubin needs to be =1.0 x ULN.
* International normalized ratio (INR) and activated partial thromboplastin time (or partial thromboplastin time) =1.5 x ULN. Prothrombin time (PT) =1.5 x ULN may be used instead of INR for sites whose labs do not report INR.
* Estimated glomerular filtration rate based on Modification of Diet in Renal Disease (MDRD) calculation =30 mL/min/1.73 m^2.
* Fridericia's Correction Formula (QTcF) =470 msec.
Minimum age
18 Years
Maximum age
100 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Active brain metastases. Participants who have had brain metastases resected or have received radiation therapy ending at least 4 weeks prior to study day 1 are eligible if they meet all of the following criteria: a) residual neurological symptoms grade =2; b) on stable doses of dexamethasone or equivalent for at least 2 weeks, if applicable; and c) follow-up magnetic resonance imaging (MRI) performed within 28 days of day 1 shows no progression or new lesions appearing.
* History or presence of hematological malignancies unless curatively treated with no evidence of disease =2 years.
* History of other malignancy within the past 3 years, with the following exceptions:

* Malignancy treated with curative intent and with no known active disease present for =3 years before enrollment and felt to be at low risk for recurrence by the treating physician.
* Adequately treated non-melanoma skin cancer or lentigo maligna without evidence of disease.
* Adequately treated cervical carcinoma in situ without evidence of disease.
* Adequately treated breast ductal carcinoma in situ without evidence of disease.
* Prostatic intraepithelial neoplasia without evidence of prostate cancer.
* Adequately treated urothelial papillary non-invasive carcinoma or carcinoma in situ.
* Leptomeningeal disease.
* Significant gastrointestinal (GI) disorder that results in significant malabsorption, requirement for intravenous (IV) alimentation, or inability to take oral medication.
* History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
* Significant cardiovascular disease, such as New York Heart Association cardiac disease (Class II or greater), myocardial infarction within 6 months prior to randomization, unstable arrhythmias or unstable angina.
* Previous treatment with a KRAS G12C inhibitor.

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
Parallel
Other design features
Phase
Phase 3
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,SA
Recruitment hospital [1] 0 0
Chris OBrien Lifehouse - Camperdown
Recruitment hospital [2] 0 0
GenesisCare -North Shore (Oncology) - St Leonards
Recruitment hospital [3] 0 0
Westmead Hospital - Westmead
Recruitment hospital [4] 0 0
The Queen Elizabeth Hospital - Woodville South
Recruitment postcode(s) [1] 0 0
2050 - Camperdown
Recruitment postcode(s) [2] 0 0
2065 - St Leonards
Recruitment postcode(s) [3] 0 0
2145 - Westmead
Recruitment postcode(s) [4] 0 0
5011 - Woodville South
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
Alabama
Country [2] 0 0
United States of America
State/province [2] 0 0
California
Country [3] 0 0
United States of America
State/province [3] 0 0
District of Columbia
Country [4] 0 0
United States of America
State/province [4] 0 0
Florida
Country [5] 0 0
United States of America
State/province [5] 0 0
Georgia
Country [6] 0 0
United States of America
State/province [6] 0 0
Michigan
Country [7] 0 0
United States of America
State/province [7] 0 0
New York
Country [8] 0 0
United States of America
State/province [8] 0 0
North Carolina
Country [9] 0 0
United States of America
State/province [9] 0 0
Ohio
Country [10] 0 0
United States of America
State/province [10] 0 0
Pennsylvania
Country [11] 0 0
United States of America
State/province [11] 0 0
Tennessee
Country [12] 0 0
United States of America
State/province [12] 0 0
Texas
Country [13] 0 0
France
State/province [13] 0 0
Lyon Cédex 3
Country [14] 0 0
France
State/province [14] 0 0
Montpellier Cedex 5
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Pessac
Country [17] 0 0
Germany
State/province [17] 0 0
Berlin
Country [18] 0 0
Germany
State/province [18] 0 0
Dresden
Country [19] 0 0
Germany
State/province [19] 0 0
Goettingen
Country [20] 0 0
Germany
State/province [20] 0 0
Muenchen
Country [21] 0 0
Germany
State/province [21] 0 0
Tuebingen
Country [22] 0 0
Greece
State/province [22] 0 0
Athens
Country [23] 0 0
Greece
State/province [23] 0 0
Heraklion - Crete
Country [24] 0 0
Greece
State/province [24] 0 0
Patra
Country [25] 0 0
Greece
State/province [25] 0 0
Thessaloniki
Country [26] 0 0
Italy
State/province [26] 0 0
Brescia
Country [27] 0 0
Italy
State/province [27] 0 0
Catania
Country [28] 0 0
Italy
State/province [28] 0 0
Confreria (CN)
Country [29] 0 0
Italy
State/province [29] 0 0
Firenze
Country [30] 0 0
Italy
State/province [30] 0 0
Genova
Country [31] 0 0
Italy
State/province [31] 0 0
La Spezia
Country [32] 0 0
Italy
State/province [32] 0 0
Lecce
Country [33] 0 0
Italy
State/province [33] 0 0
Milano
Country [34] 0 0
Italy
State/province [34] 0 0
Monserrato CA
Country [35] 0 0
Italy
State/province [35] 0 0
Napoli
Country [36] 0 0
Italy
State/province [36] 0 0
Novara
Country [37] 0 0
Italy
State/province [37] 0 0
Padova
Country [38] 0 0
Italy
State/province [38] 0 0
Pisa
Country [39] 0 0
Italy
State/province [39] 0 0
Potenza
Country [40] 0 0
Italy
State/province [40] 0 0
Reggio Emilia
Country [41] 0 0
Italy
State/province [41] 0 0
Roma (RM)
Country [42] 0 0
Italy
State/province [42] 0 0
Roma
Country [43] 0 0
Italy
State/province [43] 0 0
Tricase
Country [44] 0 0
Italy
State/province [44] 0 0
Vicenza
Country [45] 0 0
Japan
State/province [45] 0 0
Aichi
Country [46] 0 0
Japan
State/province [46] 0 0
Chiba
Country [47] 0 0
Japan
State/province [47] 0 0
Ehime
Country [48] 0 0
Japan
State/province [48] 0 0
Fukuoka
Country [49] 0 0
Japan
State/province [49] 0 0
Hokkaido
Country [50] 0 0
Japan
State/province [50] 0 0
Hyogo
Country [51] 0 0
Japan
State/province [51] 0 0
Kanagawa
Country [52] 0 0
Japan
State/province [52] 0 0
Osaka
Country [53] 0 0
Japan
State/province [53] 0 0
Saitama
Country [54] 0 0
Japan
State/province [54] 0 0
Shizuoka
Country [55] 0 0
Japan
State/province [55] 0 0
Tokyo
Country [56] 0 0
Korea, Republic of
State/province [56] 0 0
Seoul
Country [57] 0 0
Mexico
State/province [57] 0 0
Distrito Federal
Country [58] 0 0
Mexico
State/province [58] 0 0
Ciudad de Mexico
Country [59] 0 0
Spain
State/province [59] 0 0
Andalucía
Country [60] 0 0
Spain
State/province [60] 0 0
Cantabria
Country [61] 0 0
Spain
State/province [61] 0 0
Cataluña
Country [62] 0 0
Spain
State/province [62] 0 0
Comunidad Valenciana
Country [63] 0 0
Spain
State/province [63] 0 0
Galicia
Country [64] 0 0
Spain
State/province [64] 0 0
Navarra
Country [65] 0 0
Spain
State/province [65] 0 0
Madrid
Country [66] 0 0
Taiwan
State/province [66] 0 0
Kaohsiung
Country [67] 0 0
Taiwan
State/province [67] 0 0
Tainan
Country [68] 0 0
Taiwan
State/province [68] 0 0
Taipei
Country [69] 0 0
Taiwan
State/province [69] 0 0
Taoyuan
Country [70] 0 0
United Kingdom
State/province [70] 0 0
Glasgow
Country [71] 0 0
United Kingdom
State/province [71] 0 0
London
Country [72] 0 0
United Kingdom
State/province [72] 0 0
Maidstone
Country [73] 0 0
United Kingdom
State/province [73] 0 0
Northwood
Country [74] 0 0
United Kingdom
State/province [74] 0 0
Sutton

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: http://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.