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

JRCT ID: jRCT2011210078

Registered date:26/03/2022

Basic Information

• Recruitment status: Not Recruiting
• Health condition(s) or Problem(s) studied: Colorectal Cancer (CRC)
• Date of first enrollment: 19/04/2022
• Target sample size: 153
• Countries of recruitment: United States,Japan,Australia,Japan,France,Japan,Germany,Japan,Greece,Japan,Italy,Japan,Korea,Japan,Spain,Japan
• Study type: Interventional

Intervention(s)

Experimental: Arm A: Sotorasib 960 mg once daily (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

Outcome(s)

• Primary Outcome: 1. Progression-free Survival (PFS) [ Time Frame: Approximately 2 years ]

Secondary Outcome

1. Overall Survival (OS) [ Time Frame: Approximately 2 years ]
2. Objective Response Rate (ORR) [ Time Frame: Approximately 2 years ]
3. Duration of Response (DOR) [ Time Frame: Approximately 2 years ]
4. Time to Response (TTR) [ Time Frame: Approximately 2 years ]
5. Disease Control Rate (DCR) [ Time Frame: Approximately 2 years ]
6. Investigator Assessed ORR [ Time Frame: Approximately 2 years ]
7. Investigator Assessed PFS [ Time Frame: Approximately 2 years ]
8. Number of Participants with a Treatment-emergent Adverse Event (TEAE) [ Time Frame: Approximately 2 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.
9. 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.
10. 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.
11. 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.
12. 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 to7, 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.
13. 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.
14. 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.
15. 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.
16. 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. Itis 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'.
17. 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".
18. 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.
19. Maximum Plasma Concentration (Cmax) of Sotorasib [ Time Frame: Day 1 to approximately 2 years ]
20. Cmax of Panitumumab [ Time Frame: Day 1 to approximately 2 years ]
21. Area Under the Plasma Concentration-time Curve (AUC) of Sotorasib [ Time Frame: Day 1 to approximately 2 years ]
22. AUC of Panitumumab [ Time Frame: Day 1 to approximately 2 years ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: <= 100age old
• Gender: Both

Include criteria

1. Participant has provided informed consent/assent prior to initiation of any study specific activities/procedures.
2. Age >=18 years.
3. Pathologically documented metastatic colorectal adenocarcinoma with Kirsten rat sarcoma (KRAS) p.G12C mutation as determined by central testing.
4. 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.
5. 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.
6. Eastern Cooperative Oncology Group (ECOG) Performance Status of <=2.
7. Life expectancy of >3 months, in the opinion of the investigator.
8. Adequate hematologic and end-organ function, defined as the following within 10 days prior to randomization:
- 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, direct bilirubin <=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.
9. Fridericia's Correction Formula (QTcF) <=470 msec.

Exclude criteria

1. 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.
2. History or presence of hematological malignancies unless curatively treated with no evidence of disease >=2 years.
3. 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.
4. Leptomeningeal disease.
5. Significant gastrointestinal (GI) disorder that results in significant malabsorption, requirement for intravenous (IV) alimentation, or inability to take oral medication.
6. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis.
7. 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.
8. Previous treatment with a KRAS G12C inhibitor.

Related Information

• Primary Sponsor: Nakatani Iwam
• Secondary ID(s): NCT05198934