Clinical trial NCT03600883: 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)
Official 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)
Study type: INTERVENTIONAL
Overall status: ACTIVE_NOT_RECRUITING
Phase: PHASE1
PHASE2
Conditions: KRAS p.G12C Mutant Advanced Solid Tumors
Lead sponsor: Amgen
Sponsor class: INDUSTRY
First posted: 2018-07-26
Enrollment: 713
Sex: ALL
Minimum age (years): 18
Maximum age (years): 100
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SEQUENTIAL
Primary purpose: TREATMENT

Brief summary: Evaluate the safety and tolerability of sotorasib in adult subjects with KRAS p.G12C mutant advanced solid tumors.

Estimate the maximum tolerated dose (MTD) and/or a recommended phase 2 dose (RP2D) in adult subjects with KRAS p.G12C mutant advanced solid tumors.


Eligibility criteria: 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.

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.

Primary outcomes:
measure: Primary: Number of subjects with treatment-emergent adverse events
timeFrame: 24 Months
measure: Primary: Number of subjects with treatment-related adverse events
timeFrame: 24 Months
measure: Primary: Number of subjects with grade ≥3 treatment-emergent adverse events
timeFrame: 24 Months
measure: Primary: Number of subjects with serious adverse events
timeFrame: 24 Months
measure: Primary: Number of subjects with adverse events of interest
timeFrame: 24 Months
measure: Primary: Number of subjects with clinically significant changes in vital signs
timeFrame: Baseline to 24 Months
measure: Primary: Number of subjects with clinically significant changes in physical examination results
timeFrame: Baseline to 24 Months
measure: Primary: Number of subjects with clinically significant changes on electrocardiograms (ECGs)
timeFrame: Baseline to 24 Months
measure: Primary: Number of subjects with clinically significant changes in clinical laboratory values
timeFrame: Baseline to 24 Months
measure: Primary: Number of subjects with dose-limiting toxicities (DLTs)
timeFrame: 21 Days
measure: Primary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Primary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Primary: Disease control as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Primary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Primary: Time to response (TTR) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
Secondary outcomes:
measure: Secondary: Plasma concentration (Cmax) of sotorasib
timeFrame: 15 Weeks
measure: Secondary: Plasma concentration (Cmax) of midazolam
timeFrame: 16 Days
measure: Secondary: Time to achieve Cmax (Tmax) of sotorasib
timeFrame: 15 Weeks
measure: Secondary: Area under the plasma concentration-time curve (AUC) of sotorasib
timeFrame: 15 Weeks
measure: Secondary: Area under the plasma concentration-time curve (AUC) of midazolam
timeFrame: 16 Days
measure: Secondary: Clearance of midazolam from the plasma
timeFrame: 16 Days
measure: Secondary: Terminal half-life (t1/2) of midazolam
timeFrame: 16 Days
measure: Secondary: Objective response rate (ORR) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Secondary: Duration of response (DOR) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Secondary: Disease control as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Secondary: Progression-free survival (PFS) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Secondary: Duration of stable disease (SD) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Secondary: Depth of response (best percentage change from baseline in lesion sum diameters) as assessed by RECIST 1.1 criteria
timeFrame: Baseline to 24 Months
measure: Secondary: Time to response (TTR) as assessed by RECIST 1.1 criteria
timeFrame: 24 Months
measure: Secondary: Overall survival (OS)
timeFrame: 24 Months
measure: Secondary: sotorasib exposure and QTc interval relationship
timeFrame: 24 Months
measure: Secondary: Progression-free survival (PFS) at 6 months
timeFrame: 6 Months
measure: Secondary: Progression-free survival (PFS) at 12 months
timeFrame: 12 Months
measure: Secondary: Overall survival (OS) at 12 months
timeFrame: 12 Months
measure: Secondary: Number of subjects with treatment-emergent adverse events
timeFrame: 24 Months
measure: Secondary: Number of subjects with grade ≥3 treatment-emergent adverse events
timeFrame: 24 Months
measure: Secondary: Impact of treatment on disease-related symptoms and health related quality of life (HRQOL) as assessed by EORTC QLQ-C30
timeFrame: 24 Months
measure: 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)
timeFrame: 24 Months
measure: 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
timeFrame: 24 Months
measure: Secondary: Impact of treatment on disease-related symptoms and HRQOL as assessed by Patient Global Impression of Severity (PGIS)
timeFrame: 24 Months
measure: 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
timeFrame: 24 Months
measure: Secondary: Treatment-related symptoms and impact on the subject as assessed by EORTC QLQ-C30
timeFrame: 24 Months
measure: 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)
timeFrame: 24 Months
measure: 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)
timeFrame: 24 Months
measure: Secondary: Change from baseline in physical function as assessed by EORTC QLQ-C30
timeFrame: Baseline to 24 Months
Other outcomes:
Locations:
city: Duarte
country: United States
facility: City of Hope National Medical Center
state: California
city: Los Angeles
country: United States
facility: University of California Los Angeles
state: California
city: San Francisco
country: United States
facility: University of California at SF
state: California
city: Santa Monica
country: United States
facility: Sarcoma Oncology Research Center LLC
state: California
city: Denver
country: United States
facility: Rocky Mountain Cancer Centers
state: Colorado
city: Denver
country: United States
facility: Sarah Cannon Research Institute at HealthONE
state: Colorado
city: New Haven
country: United States
facility: Smilow Cancer Hospital at Yale New Haven
state: Connecticut
city: Newark
country: United States
facility: Medical Oncology Hematology Consultants Helen F Graham Cancer Center
state: Delaware
city: Gainesville
country: United States
facility: University of Florida Health
state: Florida
city: Orlando
country: United States
facility: AdventHealth Orlando Infusion Center
state: Florida
city: Tampa
country: United States
facility: Moffitt Cancer Center
state: Florida
city: Atlanta
country: United States
facility: Winship Cancer Institute
state: Georgia
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Bethesda
country: United States
facility: American Oncology Partners of Maryland, PA
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Ann Arbor
country: United States
facility: University of Michigan
state: Michigan
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Saint Louis
country: United States
facility: Washington University
state: Missouri
city: Buffalo
country: United States
facility: Roswell Park Cancer Institute
state: New York
city: New York
country: United States
facility: Laura and Isaac Perlmutter Cancer Center at New York University Langone
state: New York
city: New York
country: United States
facility: Memorial Sloan Kettering Cancer Center
state: New York
city: Durham
country: United States
facility: Duke University Medical Center, Morris Cancer Clinic
state: North Carolina
city: Cleveland
country: United States
facility: University Hospitals Cleveland Medical Center
state: Ohio
city: Cleveland
country: United States
facility: Cleveland Clinic
state: Ohio
city: Philadelphia
country: United States
facility: University of Pennsylvania
state: Pennsylvania
city: Philadelphia
country: United States
facility: Fox Chase Cancer Center
state: Pennsylvania
city: Pittsburgh
country: United States
facility: University of Pittsburgh Medical Center Cancer Pavillion
state: Pennsylvania
city: Spartanburg
country: United States
facility: Gibbs Cancer Center and Research Institute - Spartanburg
state: South Carolina
city: Nashville
country: United States
facility: Vanderbilt University Ingram Cancer Center
state: Tennessee
city: Austin
country: United States
facility: Texas Oncology - Austin Central
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor
state: Texas
city: Dallas
country: United States
facility: University of Texas Southwestern Medical Center
state: Texas
city: Houston
country: United States
facility: University of Texas MD Anderson Cancer Center
state: Texas
city: Salt Lake City
country: United States
facility: Huntsman Cancer Institute
state: Utah
city: Fairfax
country: United States
facility: US Oncology Research Investigational Products Center
state: Virginia
city: Fairfax
country: United States
facility: Virginia Cancer Specialists PC
state: Virginia
city: Salem
country: United States
facility: Blue Ridge Cancer Care
state: Virginia
city: Seattle
country: United States
facility: Seattle Cancer Care Alliance
state: Washington
city: Randwick
country: Australia
facility: Scientia Clinical Research Ltd
state: New South Wales
city: Woolloongabba
country: Australia
facility: Princess Alexandra Hospital
state: Queensland
city: Woodville South
country: Australia
facility: The Queen Elizabeth Hospital
state: South Australia
city: Parkville
country: Australia
facility: Peter MacCallum Cancer Centre
state: Victoria
city: Graz
country: Austria
facility: Medizinische Universitaet Graz
city: Innsbruck
country: Austria
facility: Medizinische Universitaet Innsbruck
city: Krems
country: Austria
facility: Universitaetsklinikum Krems
city: Wien
country: Austria
facility: Universitaetsklinikum Allgemeines Krankenhaus Wien
city: Wien
country: Austria
facility: Krankenhaus Nord - Klinik Floridsdorf
city: Brussels
country: Belgium
facility: Institut Jules Bordet
city: Charleroi
country: Belgium
facility: Grand Hopital de Charleroi
city: Edegem
country: Belgium
facility: Universitair Ziekenhuis Antwerpen
city: Genk
country: Belgium
facility: Ziekenhuis Oost-Limburg
city: Gent
country: Belgium
facility: Universitair Ziekenhuis Gent
city: Hasselt
country: Belgium
facility: Jessa Ziekenhuis - Campus Virga Jesse
city: Leuven
country: Belgium
facility: Universitair Ziekenhuis Leuven - Campus Gasthuisberg
city: Liege
country: Belgium
facility: Centre Hospitalier Universitaire de Liege
city: Roeselare
country: Belgium
facility: AZ Delta Campus Rumbeke
city: Porto Alegre
country: Brazil
facility: Irmandade da Santa Casa de Misericordia de Porto Alegre, Nucleo de Novos Tratamentos em Cancer
state: Rio Grande Do Sul
city: Porto Alegre
country: Brazil
facility: Hospital Sao Lucas da Pontificia Universidade Catolica do Rio Grande do Sul
state: Rio Grande Do Sul
city: Sao Paulo
country: Brazil
facility: Sociedade Beneficente de Senhoras Hospital Sirio Libanes
state: São Paulo
city: Sao Paulo
country: Brazil
facility: Oncologia Rede D´Or
state: São Paulo
city: São José do Rio Preto
country: Brazil
facility: Hospital de Base de Sao Jose do Rio Preto
state: São Paulo
city: Rio de Janeiro
country: Brazil
facility: Instituto Coi
city: Calgary
country: Canada
facility: Tom Baker Cancer Centre
state: Alberta
city: Edmonton
country: Canada
facility: Cross Cancer Institute
state: Alberta
city: London
country: Canada
facility: London Regional Cancer Program, London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: The Ottawa Hospital Cancer Centre
state: Ontario
city: Toronto
country: Canada
facility: Princess Margaret Cancer Centre
state: Ontario
city: Montreal
country: Canada
facility: McGill University Health Centre Glen Site
state: Quebec
city: Bordeaux
country: France
facility: Institut Bergonie
city: Créteil
country: France
facility: Centre Hospitalier Intercommunal de Créteil
city: Marseille cedex 5
country: France
facility: Hopital de la Timone
city: Paris
country: France
facility: Institut Curie
city: Toulouse cedex 9
country: France
facility: Institut Claudius Regaud
city: Villejuif
country: France
facility: Gustave Roussy
city: Essen
country: Germany
facility: Universitätsklinikum Essen
city: Köln
country: Germany
facility: Universitatsklinikum Koln
city: München
country: Germany
facility: Klinikum der Universität München Campus Grosshadern
city: Athens
country: Greece
facility: Henry Dunant Hospital Center
city: Athens
country: Greece
facility: Metropolitan Hospital
city: Heraklion - Crete
country: Greece
facility: University Hospital of Heraklion
city: Thessaloniki
country: Greece
facility: Theagenion Cancer Hospital
city: Thessaloniki
country: Greece
facility: Agios Loukas Clinic
city: Budapest
country: Hungary
facility: Semmelweis Egyetem
city: Budapest
country: Hungary
facility: Orszagos Koranyi Pulmonologiai Intezet
city: Kaposvar
country: Hungary
facility: Somogy Megyei Kaposi Mor Oktato Korhaz
city: Szekesfehervar
country: Hungary
facility: Fejer Megyei Szent Gyorgy Egyetemi Oktato Korhaz
city: Tatabanya
country: Hungary
facility: Szent Borbala Korhaz
city: Torokbalint
country: Hungary
facility: Tudogyogyintezet Torokbalint
city: Nagoya-shi
country: Japan
facility: Aichi Cancer Center
state: Aichi
city: Kashiwa-shi
country: Japan
facility: National Cancer Center Hospital East
state: Chiba
city: Matsuyama-shi
country: Japan
facility: National Hospital Organization Shikoku Cancer Center
state: Ehime
city: Fukuoka-shi
country: Japan
facility: National Hospital Organization Kyushu Cancer Center
state: Fukuoka
city: Sapporo-shi
country: Japan
facility: National Hospital Organization Hokkaido Cancer Center
state: Hokkaido
city: Kawasaki-shi
country: Japan
facility: St Marianna University Hospital
state: Kanagawa
city: Yokohama-shi
country: Japan
facility: Kanagawa Prefectural Hospital Organization Kanagawa Cancer Center
state: Kanagawa
city: Sendai-shi
country: Japan
facility: Sendai Kousei Hospital
state: Miyagi
city: Niigata-shi
country: Japan
facility: Niigata Cancer Center Hospital
state: Niigata
city: Okayama-shi
country: Japan
facility: Okayama University Hospital
state: Okayama
city: Hirakata-shi
country: Japan
facility: Kansai Medical University Hospital
state: Osaka
city: Osaka-shi
country: Japan
facility: Osaka International Cancer Institute
state: Osaka
city: Sunto-gun
country: Japan
facility: Shizuoka Cancer Center
state: Shizuoka
city: Koto-ku
country: Japan
facility: The Cancer Institute Hospital of Japanese Foundation for Cancer Research
state: Tokyo
city: Wakayama-shi
country: Japan
facility: Wakayama Medical University Hospital
state: Wakayama
city: Goyang-si Gyeonggi-do
country: Korea, Republic of
facility: National Cancer Center
city: Seongnam-si, Gyeonggi-do
country: Korea, Republic of
facility: Seoul National University Bundang Hospital
city: Seoul
country: Korea, Republic of
facility: Seoul National University Hospital
city: Seoul
country: Korea, Republic of
facility: Severance Hospital Yonsei University Health System
city: Seoul
country: Korea, Republic of
facility: Asan Medical Center
city: Seoul
country: Korea, Republic of
facility: Samsung Medical Center
city: Seoul
country: Korea, Republic of
facility: The Catholic University of Korea Seoul St Marys Hospital
city: Lisboa
country: Portugal
facility: Fundacao Champalimaud
city: Lisboa
country: Portugal
facility: Centro Hospitalar Universitario de Lisboa Norte EPE - Hospital Pulido Valente
city: Matosinhos
country: Portugal
facility: Unidade Local de Saude de Matosinhos, EPE - Hospital Pedro Hispano
city: Porto
country: Portugal
facility: Centro Hospitalar Universitario do Porto EPE - Hospital de Santo Antonio
city: Porto
country: Portugal
facility: Hospital Cuf porto
city: Bucuresti
country: Romania
facility: Institutul Oncologic, Prof Dr Alexandru Trestioreanu
city: Cluj Napoca
country: Romania
facility: Institutul Oncologic Prof Dr Ion Chiricuta Cluj-Napoca
city: Cluj Napoca
country: Romania
facility: SC Medisprof SRL
city: Cluj Napoca
country: Romania
facility: Centrul de Radioterapie Amethyst Cluj
city: Craiova
country: Romania
facility: Centrul de Oncologie Sf Nectarie SRL
city: Iasi
country: Romania
facility: Institutul Regional de Oncologie Iasi
city: Ploiesti
country: Romania
facility: Spitalul Municipal Ploiesti
city: Timisoara
country: Romania
facility: SC Oncomed SRL
city: Badalona
country: Spain
facility: Hospital Universitari Germans Trias i Pujol
state: Cataluña
city: Valencia
country: Spain
facility: Hospital General Universitario de Valencia
state: Comunidad Valenciana
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañon
city: Madrid
country: Spain
facility: Clinica Universidad de Navarra
city: Madrid
country: Spain
facility: Fundacion Jimenez Diaz
city: Madrid
country: Spain
facility: Hospital Universitario Madrid Sanchinarro
city: Basel
country: Switzerland
facility: Universitaetsspital Basel
city: Geneve
country: Switzerland
facility: Hopitaux Universitaires de Geneve
city: Zurich
country: Switzerland
facility: Universitaetsspital Zuerich
Study officials:
affiliation: Amgen
name: MD
role: STUDY_DIRECTOR
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