Clinical Trials/NCT05198934

NCT05198934

Completed

Phase 3

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

Amgen208 sites in 6 countries160 target enrollmentApril 19, 2022

ConditionsColorectal Cancer (CRC)

InterventionsSotorasib Trifluridine and Tipiracil Panitumumab Regorafenib

DrugsSotorasib Panitumumab Trifluridine and Tipiracil Regorafenib

Overview

Phase: Phase 3
Intervention: Sotorasib
Conditions: Colorectal Cancer (CRC)
Sponsor: Amgen
Enrollment: 160
Locations: 208
Primary Endpoint: Progression-free Survival (PFS)
Status: Completed
Last Updated: 5 days ago

Overview Investigators Eligibility Criteria Arms & Interventions Outcomes Sites Similar Trials Related News

Overview

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).

Registry

clinicaltrials.gov

Start Date

April 19, 2022

End Date

April 14, 2026

Last Updated

5 days ago

Study Type

Interventional

Study Design

Parallel

Sex

All

Investigators

Sponsor

Amgen

Responsible Party

Sponsor

Eligibility Criteria

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 ≤
•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).

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.

Arms & Interventions

Arm B: Sotorasib 240 mg QD + panitumumab

Intervention: Sotorasib

Arm A: Sotorasib 960 mg QD + panitumumab

Intervention: Sotorasib

Arm C : Investigator's choice

Participants will be administered trifluridine and tipiracil, or regorafenib

Intervention: Trifluridine and Tipiracil

Arm A: Sotorasib 960 mg QD + panitumumab

Intervention: Panitumumab

Arm B: Sotorasib 240 mg QD + panitumumab

Intervention: Panitumumab

Arm C : Investigator's choice

Participants will be administered trifluridine and tipiracil, or regorafenib

Intervention: Regorafenib

Outcomes

Primary Outcomes

Progression-free Survival (PFS)

Time Frame: Approximately 3 years

Secondary Outcomes

Objective Response Rate (ORR)(Approximately 3 years)
Investigator Assessed PFS(Approximately 3 years)
Change from Baseline in Global Health Status as Measured by Questions 29 and 30 of the EORTC QLQ-C30(Baseline and Week 8)
Change from Baseline For All Subscales of the BPI(Baseline and Week 8)
Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib(Day 1 to approximately 2 years)
Time to Response (TTR)(Approximately 3 years)
Change from Baseline For All Subscales and Domains of EORTC QLQ-C30(Baseline and Week 8)
Overall Survival (OS)(Approximately 3 years)
Investigator Assessed ORR(Approximately 3 years)
Change from Baseline in Fatigue Severity as Measured by Item 3 of the Brief Fatigue Inventory (BFI)(Baseline and Week 8)
AUC of Panitumumab(Day 1 to approximately 2 years)
Change from Baseline in Pain Severity as Measured by Item 3 of the Brief Pain Inventory (BPI)(Baseline and Week 8)
Change from Baseline For All Subscales of the BFI(Baseline and Week 8)
Change from Baseline in Visual Analog Scale (VAS) Scores as Measured by EuroQol-5D level 5 (EQ-5D-5L)(Baseline and Week 8)
Average Score on Single Question on Symptom Bother GP5 from Functional Assessment of Cancer Therapy - General (FACT-G)(Approximately 2 years)
Maximum Plasma Concentration (Cmax) of Sotorasib(Day 1 to approximately 2 years)
Duration of Response (DOR)(Approximately 3 years)
Disease Control Rate (DCR)(Approximately 3 years)
Number of Participants with a Treatment-emergent Adverse Event (TEAE)(Approximately 3 years)
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)(Baseline and Week 8)
Average Score of Patient Global Impression of Change (PGIC)(Approximately 2 years)
Cmax of Panitumumab(Day 1 to approximately 2 years)