Substudy 03C is part of a larger research study that is testing experimental treatments for renal cell carcinoma (RCC). The larger study is the umbrella study (U03). The goal of substudy 03C is to evaluate the safety and efficacy of experimental combinations of investigational agents in participants with clear cell renal cell carcinoma (ccRCC) who have recurrent disease during or after anti-programmed cell death 1/programmed cell death ligand 1 (PD-\[L\]1) adjuvant therapy. This substudy will have two phases: a safety lead-in phase and an efficacy phase. The safety lead-in phase will be used to demonstrate a tolerable safety profile for the combination of investigational agents. There will be no hypothesis testing in this study
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
TREATMENT
Masking
SINGLE
Enrollment
140
Oral Tablet
Oral Tablet
UCSF Medical Center at Mission Bay ( Site 5008)
San Francisco, California, United States
RECRUITINGPerlmutter Cancer Center at NYU Langone Hospital - Long Island ( Site 5026)
Mineola, New York, United States
RECRUITINGLaura and Isaac Perlmutter Cancer Center ( Site 5016)
New York, New York, United States
RECRUITINGMemorial Sloan Kettering Cancer Center ( Site 5002)
New York, New York, United States
Safety Lead In Phase: Number of participants who experience one or more dose-limiting toxicities (DLTs)
DLTs are defined as any of a pre-specified list of toxicities if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma, etc.
Time frame: Up to approximately 21 days
Safety Lead In Phase: Number of participants who experience one or more adverse events (AEs)
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.
Time frame: Up to approximately 74 months
Safety Lead In Phase: Number of participants who discontinue study treatment due to an AE
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.
Time frame: Up to approximately 74 months
Efficacy Phase: Number of participants who experience one or more DLTs
DLTs are defined as any of a pre-specified list of toxicities if assessed by the investigator to be possibly, probably, or definitely related to study treatment administration, excluding toxicities clearly not related to the drug, such as disease progression, environmental factors, unrelated trauma, etc.
Time frame: Up to approximately 21 days
Efficacy Phase: Number of participants who experience one or more AEs
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.
Time frame: Up to approximately 74 months
Efficacy Phase: Number of participants who discontinue study treatment due to an AE
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.
Time frame: Up to approximately 74 months
Efficacy Phase: Objective Response Rate (ORR)
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.
Time frame: Up to approximately 74 months
Efficacy Phase: Duration of response (DOR)
For participants who demonstrate a confirmed CR (disappearance of all target lesions) or PR (at least a 30% decrease in the sum of diameters of target lesions) per 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 BICR will be presented.
Time frame: Up to approximately 74 months
Efficacy Phase: Progression-free survival (PFS)
PFS is defined as the time from first dose of study treatment to the first documented progressive disease (PD) or death due to any cause, whichever occurs first as assessed by 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 BICR will be presented.
Time frame: Up to approximately 74 months
Efficacy Phase: Overall survival (OS)
OS is defined as time from first dose of study treatment to death due to any cause.
Time frame: Up to approximately 74 months
Efficacy Phase: Clinical benefit rate (CBR)
CBR is defined as the percentage of participants who have achieved stable disease (SD: Neither sufficient shrinkage to qualify for PR \[at least a 30% decrease in the sum of diameters of target lesions\] nor sufficient increase to qualify for PD) of ≥6 months or confirmed CR (disappearance of all target lesions) or PR 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. The CBR as assessed by BICR will be presented.
Time frame: Up to approximately 74 months
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Duke Cancer Institute ( Site 5015)
Durham, North Carolina, United States
RECRUITINGInstitut Claudius Regaud ( Site 5200)
Toulouse, Haute-Garonne, France
RECRUITINGCentre Eugene Marquis ( Site 5205)
Rennes, Ille-et-Vilaine, France
RECRUITINGInstitut De Cancerologie De Lorraine ( Site 5204)
Vandœuvre-lès-Nancy, Meurthe-et-Moselle, France
RECRUITINGGustave Roussy ( Site 5202)
Villejuif, Île-de-France Region, France
RECRUITINGRambam Health Care Campus ( Site 5500)
Haifa, Israel
RECRUITING...and 13 more locations