Renal Cell Carcinoma
Conditions
Keywords
Carcinoma, Renal cell, Belzutifan, Zanzalintinib
Brief summary
Researchers are looking for more ways to treat advanced renal cell carcinoma (RCC) that is recurrent. Researchers want to learn if recurrent advanced renal cell carcinoma (RCC) responds (gets smaller or goes away) after treatment with belzutifan (MK-6482) and zanzalintinib compared to cabozantinib. The goal of this study is to learn if: People who take belzutifan and zanzalintinib live longer overall and without the cancer getting worse than people who take cabozantinib.
Interventions
DRUGBelzutifan
Administered orally QD
DRUGZanzalintinib
Administered orally QD
DRUGCabozantinib
Administered orally QD
Sponsors
Merck Sharp & Dohme LLC
Exelixis
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
The main inclusion criteria include but are not limited to the following: * Has a histologically confirmed diagnosis of unresectable, advanced renal cell cancer (RCC) with clear cell component (with or without sarcomatoid features) i.e., Stage IV renal cell cancer per American Joint Committee on Cancer (AJCC) (8th Edition) * Has measurable disease per Response Evaluation Criteria in Solid Tumors 1.1 (RECIST 1.1) * Has disease recurrence during adjuvant anti-programmed cell death 1/programmed cell death ligand 1 (PD-1/L1) therapy or recurrence ≤24 months following the last dose of adjuvant anti-PD-1/L1 therapy * Has received no other prior systemic therapy for their RCC except for their adjuvant anti-PD-1/L1 therapy
Exclusion criteria
The main
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Progression Free Survival (PFS) | Up to approximately 73 months | PFS is defined as the time from randomization to the first documented progressive disease (PD) or death due to any cause, whichever occurs first. PD will be assessed by Response Criteria in Solid Tumors Version 1.1 (RECIST 1.1). PD is defined as ≥20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of ≥5 mm. The appearance of one or more new lesions is also considered PD. PFS as assessed by blinded independent central review (BICR) will be presented. |
| Overall Survival (OS) | Up to approximately 73 months | OS is defined as the time from randomization to death due to any cause. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Objective Response Rate (ORR) | Up to approximately 73 months | ORR is defined as the percentage of participants with Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1). The percentage of participants who experience CR or PR as assessed by Blinded Independent Central Review (BICR) will be presented. |
| Duration of Response (DOR) | Up to approximately 73 months | For participants who demonstrate a confirmed Complete Response (CR: disappearance of all target lesions) or Partial Response (PR: at least a 30% decrease in the sum of diameters of target lesions) per Response Evaluation Criteria In Solid Tumors Version 1.1 (RECIST 1.1), DOR is defined as the time from first documented evidence of CR or PR until progressive disease (PD) or death. Per RECIST 1.1, PD is defined as at least a 20% increase in the sum of diameters of target lesions. In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions is also considered PD. DOR as assessed by Blinded Independent Central Review (BICR) will be presented. |
| Number of Participants Who Experience One or More Adverse Events (AEs) | Up to approximately 73 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who experienced an AE will be reported. |
| Number of Participants Who Discontinue Study Treatment due to an AE | Up to approximately 73 months | An AE is any untoward medical occurrence in a clinical study participant, temporally associated with the use of study intervention, whether or not considered related to the study intervention. An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory finding), symptom, or disease (new or exacerbated) temporally associated with the use of a study intervention. The number of participants who discontinue the study treatment due to an AE will be reported. |
| Change From Baseline in European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire 30 (EORTC QLQ-C30) Global Health/Health-Related Quality of Life (HRQoL) Items 29 and 30 Combined Score | Up to approximately 25 months | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to the questions regarding Global Health Status (GHS; "How would you rate your overall health during the past week?") and Quality of Life (QoL; "How would you rate your overall quality of life during the past week?") are scored on a 7-point scale (1= Very poor to 7=Excellent), then summed. Summed raw scores are standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better overall outcome. |
| Change From Baseline in EORTC QLC-C30 Physical Functioning Items 1-5 Score | Up to approximately 25 months | The EORTC QLQ-C30 is a cancer specific health-related quality-of life (QoL) questionnaire. Participant responses to 5 questions about their physical functioning (Items 1-5) are scored on a 4-point scale (1=Not at All to 4=Very Much). The combined score of items 1 to 5 was computed by averaging the raw scores of the 5 items and then applying a linear transformation to standardize the average score, so that the combined scores range from 0-100. A higher score indicates a better outcome. |
| Change From Baseline in EORTC QLQ-C30 Role Functioning Items 6-7 Score | Up to approximately 25 months | The EORTC QLQ-C30 is a questionnaire to assess the overall quality of life of cancer patients. Participant responses to 2 questions about their role functioning are scored on a 4-point scale (1=Not at All to 4=Very Much). Summed raw scores are standardized by linear transformation so that scores ranged from 0 to 100, with a higher score indicating a better level of functioning. |
| Change From Baseline in Functional Assessment of Cancer Therapy-Kidney Symptom Index-Disease-related Symptoms (FKSI-DRS) Items 1-9 Score | Up to approximately 25 months | The FKSI-DRS index consists of a 9-item questionnaire that assesses the extent of participant symptoms from kidney cancer. Responses are scored on a 5-point scale (0=Not at all to 4=Very much) and summed to generate an index symptom score. These scores can range from 0 to 36, with a higher score indicating more favorable kidney cancer symptom status. |
| Time From Baseline to First Deterioration in EORTC-QLC-C30 Global Health/HRQoL Score | Up to approximately 25 months | Time to True Deterioration (TTD) is defined as the time from baseline to the first onset of a ≥10-point decrease with confirmation by the subsequent visit of a ≥10-point decrease in Items 29 and 30 scale scores. A longer TTD indicates a better outcome. TTD is reported based on the product-limit (Kaplan-Meier) method for censored data. |
| Time From Baseline to First Deterioration in EORTC-QLC-C30 Physical Functioning Score | Up to approximately 25 months | TTD is defined as the time from baseline to the first onset of a ≥10-point deterioration (decrease) from baseline in physical functioning score (EORTC QLQ-C30 Items 1-5). Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10-point negative change (decrease) from baseline in physical functioning score will be presented. A longer TTD indicates a better outcome. |
| Time From Baseline to First Deterioration in EORTC-QLC-C30 Role Functioning Score | Up to approximately 25 months | TTD is defined as the time from baseline to the first onset of a ≥10-point negative change (decrease) from baseline in role functioning (EORTC QLQ-C30 Items 6 and 7) score. Using linear transformation, raw scores are standardized, so that scores range from 0 to 100. The TTD, as assessed based on a ≥10 point negative change (decrease) from baseline in role functioning score, will be presented. A longer TTD indicates a better outcome. |
| Time From Baseline to First Deterioration in FKSI-DRS Score | Up to approximately 25 months | TTD is defined as time from the first dose of study treatment to the date of deterioration of FKSI-DRS Score. Each item is scored on a 5-point scale (0=not at all to 4=very much). FKSI-DRS total score ranged from 0 (most severe symptoms) to 36 (no symptoms) with a higher score indicating a better outcome. Deterioration is defined as a 3-point decrease (i.e. lower score) in symptom score and the time to true deterioration is the time to first onset of 3 or more decreases from baseline with confirmation under right-censoring rule (the last observation). A longer TTD indicates a better outcome. |
Countries
Argentina, Australia, Austria, Belgium, Brazil, Chile, Croatia, Czechia, Denmark, France, Germany, Greece, Hong Kong, Ireland, Italy, Mexico, Poland, Singapore, South Korea, Spain, Taiwan, United Kingdom, United States
Contacts
CONTACTToll Free Number
STUDY_DIRECTORMedical Director
Merck Sharp & Dohme LLC
Outcome results
None listed