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Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation (CodeBreak300)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT05198934
Recruitment Status : Active, not recruiting
First Posted : January 20, 2022
Last Update Posted : May 13, 2024
Sponsor:
Information provided by (Responsible Party):
Amgen

Tracking Information
First Submitted Date  ICMJE January 6, 2022
First Posted Date  ICMJE January 20, 2022
Last Update Posted Date May 13, 2024
Actual Study Start Date  ICMJE April 19, 2022
Estimated Primary Completion Date March 12, 2025   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 12, 2023)
Progression-free Survival (PFS) [ Time Frame: Approximately 3 years ]
Original Primary Outcome Measures  ICMJE
 (submitted: January 6, 2022)
Progression-free Survival (PFS) [ Time Frame: Approximately 2 years ]
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: May 12, 2023)
  • Overall Survival (OS) [ Time Frame: Approximately 3 years ]
  • Objective Response Rate (ORR) [ Time Frame: Approximately 3 years ]
  • Duration of Response (DOR) [ Time Frame: Approximately 3 years ]
  • Time to Response (TTR) [ Time Frame: Approximately 3 years ]
  • Disease Control Rate (DCR) [ Time Frame: Approximately 3 years ]
  • Investigator Assessed ORR [ Time Frame: Approximately 3 years ]
  • Investigator Assessed PFS [ Time Frame: Approximately 3 years ]
  • Number of Participants with a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Approximately 3 years ]
    A TEAE is any untoward medical occurrence in a clinical study participant following first dose of treatment irrespective of a causal relationship with the study treatment. Any clinically significant changes in vital signs and clinical laboratory tests following first dose will be recorded as TEAEs.
  • Change from Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory (BFI) [ Time Frame: Baseline and Week 8 ]
    Item 3 of the BFI records a participants' fatigue on a scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.
  • Change from Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory (BPI) [ Time Frame: Baseline and Week 8 ]
    Item 3 of the BPI records a participants' pain on a scale from 1 to 10, where pain is mild (score of 1 to 4), moderate (score of 5 to 6), or severe (score of 7 to 10). An increase in score from baseline indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.
  • 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) [ Time Frame: Baseline and Week 8 ]
    The physical function domain of the EORTC QLQ-C30 assesses a participants' quality of life regarding their physical function on a scale from 1 to 4, with higher scores indicating a worse outcome. An increase in score from baseline indicates a worsening of physical functioning. A decrease in score from baseline indicates an improvement in physical functioning.
  • Change from Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30 [ Time Frame: Baseline and Week 8 ]
    Questions 29 and 30 of the EORTC QLQ-C30 assess a participants' global health status on a scale from 1 to 7, with higher scores indicating a better outcome. An increase in score from baseline indicates an improvement in global health status. A decrease in score from baseline indicates a worsening in global health status.
  • Change from Baseline For All Subscales of the BFI [ Time Frame: Baseline and Week 8 ]
    The BFI is a questionnaire that includes 3 items to assess fatigue severity and 5 items to assess interference due to fatigue, with each item reported on a numeric rating scale from 0 to 10. Higher scores indicate a higher severity of fatigue. An increase in score from baseline indicates a worsening of fatigue. A decrease in score from baseline indicates an improvement in fatigue.
  • Change from Baseline For All Subscales of the BPI [ Time Frame: Baseline and Week 8 ]
    The BPI is a 9-item questionnaire which includes 2 body diagrams, four items to assess pain severity, four items to assess pain interference and one question about percentage of pain relief by analgesics. The level of pain and pain interference assessed can be divided into categories based on score of mild (1 to 4), moderate (5 to 6), and severe (7 to 10). An increase in score from baseline indicates a worsening of pain. A decrease in score from baseline indicates a lessening of pain.
  • Change from Baseline For All Subscales and Domains of EORTC QLQ-C30 [ Time Frame: Baseline and Week 8 ]
    The EORTC QLQ-C30 is a self-reporting 30-item generic instrument which assesses 5 functional domains (physical, role, emotional, cognitive, social), 9 symptom scales (fatigue, nausea and vomiting, pain, dyspnea, insomnia, appetite loss, constipation, diarrhea, financial difficulties), and a global health status/quality of life (QOL) scale. Higher scores indicate a worse outcome. An increase in score from baseline indicates a worsening of outcome. A decrease in score from baseline indicates an improvement in outcome.
  • Change from Baseline in Visual Analog Scale (VAS) Scores as Measured by EuroQol-5D level 5 (EQ-5D-5L) [ Time Frame: Baseline and Week 8 ]
    The EQ-5D-5L questionnaire is a 2-page, standardized instrument for use as a measure of health outcome. It is comprised of a 5-dimension health status measure and a visual analogue scale. The 5-dimension health status measure evaluates: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression based on a 5-level scale: no problems, slight problems, moderate problems, severe problems, and extreme problems. The visual analogue scale records the participant's self-rated health on a vertical, visual analogue scale where the endpoints are labelled 'Best imaginable health state' and 'Worst imaginable health state'.
  • Average Score on Single Question on Symptom Bother GP5 from Functional Assessment of Cancer Therapy - General (FACT-G) [ Time Frame: Approximately 2 years ]
    The GP5 from the FACT-G is a single item included in the Physical Well-Being subscale of the FACT-G. Responses to the item: "I am bothered by side effects of treatment" are rated on a 5-point Likert scale from "not at all" to "very much".
  • Average Score of Patient Global Impression of Change (PGIC) [ Time Frame: Approximately 2 years ]
    The PGIC scale consists of one item which measures the participants' perception of change in their condition relative to the beginning of the study. Responses are rated on a 7-item response scale ranging from very much improved to very much worse.
  • Maximum Plasma Concentration (Cmax) of Sotorasib [ Time Frame: Day 1 to approximately 2 years ]
  • Cmax of Panitumumab [ Time Frame: Day 1 to approximately 2 years ]
  • Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib [ Time Frame: Day 1 to approximately 2 years ]
  • AUC of Panitumumab [ Time Frame: Day 1 to approximately 2 years ]
Original Secondary Outcome Measures  ICMJE
 (submitted: January 6, 2022)
  • Overall Survival (OS) [ Time Frame: Approximately 2 years ]
  • Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
  • Duration of Response (DOR) [ Time Frame: Approximately 2 years ]
  • Time to Response (TTR) [ Time Frame: Approximately 2 years ]
  • Disease Control Rate (DCR) [ Time Frame: Approximately 2 years ]
  • Investigator Assessed Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
  • Investigator Assessed Progression-free Survival (PFS) [ Time Frame: Approximately 2 years ]
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Sotorasib and Panitumumab Versus Investigator's Choice for Participants With Kirsten Rat Sarcoma (KRAS) p.G12C Mutation
Official Title  ICMJE 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
Brief Summary The aim of the study is to compare progression-free survival (PFS) in previously treated participants with Kirsten rat sarcoma (KRAS) p.G12C mutated colorectal cancer (CRC) receiving sotorasib 240 mg once daily (QD) and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib), and sotorasib 960 mg QD and panitumumab vs investigator's choice (trifluridine and tipiracil, or regorafenib).
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Colorectal Cancer (CRC)
Intervention  ICMJE
  • Drug: Sotorasib
    Sotorasib will be administered orally
    Other Name: AMG 510, Lumakras, Lumykras
  • Drug: Panitumumab
    Panitumumab will be administered as intravenous (IV) infusion
    Other Name: Vectibix
  • Drug: Trifluridine and Tipiracil
    Trifluridine and Tipiracil will be administered orally
    Other Name: Lonsurf
  • Drug: Regorafenib
    Regorafenib will be administered orally
    Other Name: Stivarga
Study Arms  ICMJE
  • Experimental: Arm A: Sotorasib 960 mg QD + panitumumab
    Interventions:
    • Drug: Sotorasib
    • Drug: Panitumumab
  • Experimental: Arm B: Sotorasib 240 mg QD + panitumumab
    Interventions:
    • Drug: Sotorasib
    • Drug: Panitumumab
  • Active Comparator: Arm C : Investigator's choice
    Participants will be administered trifluridine and tipiracil, or regorafenib
    Interventions:
    • Drug: Trifluridine and Tipiracil
    • Drug: Regorafenib
Publications * Fakih MG, Salvatore L, Esaki T, Modest DP, Lopez-Bravo DP, Taieb J, Karamouzis MV, Ruiz-Garcia E, Kim TW, Kuboki Y, Meriggi F, Cunningham D, Yeh KH, Chan E, Chao J, Saportas Y, Tran Q, Cremolini C, Pietrantonio F. Sotorasib plus Panitumumab in Refractory Colorectal Cancer with Mutated KRAS G12C. N Engl J Med. 2023 Dec 7;389(23):2125-2139. doi: 10.1056/NEJMoa2308795. Epub 2023 Oct 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: March 21, 2023)
160
Original Estimated Enrollment  ICMJE
 (submitted: January 6, 2022)
153
Estimated Study Completion Date  ICMJE March 12, 2025
Estimated Primary Completion Date March 12, 2025   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 100 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Australia,   France,   Germany,   Greece,   Italy,   Japan,   Korea, Republic of,   Mexico,   Spain,   Taiwan,   United Kingdom,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05198934
Other Study ID Numbers  ICMJE 20190172
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: Yes
Plan Description: De-identified individual patient data for variables necessary to address the specific research question in an approved data sharing request
Supporting Materials: Study Protocol
Supporting Materials: Statistical Analysis Plan (SAP)
Supporting Materials: Informed Consent Form (ICF)
Supporting Materials: Clinical Study Report (CSR)
Time Frame: 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.
Access Criteria: 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.
URL: http://www.amgen.com/datasharing
Current Responsible Party Amgen
Original Responsible Party Same as current
Current Study Sponsor  ICMJE Amgen
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Study Director: MD Amgen
PRS Account Amgen
Verification Date May 2024

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP