Trial Outcomes & Findings for Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma (NCT NCT00827359)
NCT ID: NCT00827359
Last Updated: 2021-02-24
Results Overview
The biomarkers of interest are pS6 and pAkt. Expression will be classified as low, intermediate, or high based on a composite score of staining intensity and % of tumor cells staining positive. The difference in progression free survival (PFS) time in the "low" to "high" groups is analyzed. PFS is the time from start of treatment to disease progression (PD) or death (estimated by Kaplan Meier method)s. Patients without PD and alive are censored at last date patient is known PD-free. PD is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows: * \>20% increase in the sum of the diameters (SD) of target lesions, referencing the smallest SD on study (including baseline). Must be an increase of \>5 mm. * New lesions or PD of non-target lesions. Must be represent overall disease status change, not a single lesion increase. Patients with PD at the first on-treatment imaging assessment, will remain on study at investigator discretion until later confirmed.
COMPLETED
PHASE2
25 participants
Follow-up time was up to 39 months from treatment start date.
2021-02-24
Participant Flow
Participant milestones
| Measure |
Treatment
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Overall Study
STARTED
|
25
|
|
Overall Study
Treated
|
24
|
|
Overall Study
COMPLETED
|
0
|
|
Overall Study
NOT COMPLETED
|
25
|
Reasons for withdrawal
| Measure |
Treatment
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Overall Study
Progressive Diseas
|
19
|
|
Overall Study
Unacceptable Toxicity
|
5
|
|
Overall Study
Ineligible
|
1
|
Baseline Characteristics
Biomarker Trial of Everolimus in Patients With Advanced Renal Cell Carcinoma
Baseline characteristics by cohort
| Measure |
Treatment
n=24 Participants
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Age, Continuous
|
64 years
n=5 Participants
|
|
Sex: Female, Male
Female
|
8 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
16 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
23 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
0 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
23 Participants
n=5 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
|
ECOG Performance Status
00
|
15 Participants
n=5 Participants
|
|
ECOG Performance Status
01
|
9 Participants
n=5 Participants
|
|
Prior Lines of Therapy
|
2 therapies
n=5 Participants
|
|
Histology
Clear Cell
|
18 Participants
n=5 Participants
|
|
Histology
Papillary
|
4 Participants
n=5 Participants
|
|
Histology
Missing
|
2 Participants
n=5 Participants
|
|
Memorial Sloan Kettering Cancer Center Risk Class
Favorable (0 risk factors)
|
4 Participants
n=5 Participants
|
|
Memorial Sloan Kettering Cancer Center Risk Class
Intermediate (1-2 risk factors)
|
14 Participants
n=5 Participants
|
|
Memorial Sloan Kettering Cancer Center Risk Class
High (>=3 risk factors)
|
6 Participants
n=5 Participants
|
|
International Metastatic Renal-Cell Carcinoma Database Consortium Class
Favorable (0 risk factors)
|
5 Participants
n=5 Participants
|
|
International Metastatic Renal-Cell Carcinoma Database Consortium Class
Intermediate (1-2 risk factors)
|
19 Participants
n=5 Participants
|
|
International Metastatic Renal-Cell Carcinoma Database Consortium Class
High (≥3 risk factors)
|
0 Participants
n=5 Participants
|
|
Prior Nephrectomy
Yes, Radical
|
21 Participants
n=5 Participants
|
|
Prior Nephrectomy
Yes, Partial
|
1 Participants
n=5 Participants
|
|
Prior Nephrectomy
No
|
0 Participants
n=5 Participants
|
|
Prior Nephrectomy
Missing
|
2 Participants
n=5 Participants
|
|
Metastatic Sites
Bone
|
4 Participants
n=5 Participants
|
|
Metastatic Sites
Liver
|
8 Participants
n=5 Participants
|
|
Metastatic Sites
Lung
|
16 Participants
n=5 Participants
|
|
Metastatic Sites
Brain
|
0 Participants
n=5 Participants
|
|
Metastatic Sites
Renal
|
6 Participants
n=5 Participants
|
|
Metastatic Sites
Pancreas
|
3 Participants
n=5 Participants
|
|
Metastatic Sites
Lymph Nodes, Intra-Abdominal
|
11 Participants
n=5 Participants
|
|
Metastatic Sites
Lymph Node, Pulmonary
|
7 Participants
n=5 Participants
|
|
Metastatic Sites
Adrenal Glands
|
5 Participants
n=5 Participants
|
|
Metastatic Sites
Other
|
15 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Follow-up time was up to 39 months from treatment start date.Population: Phospho-Akt and phospho-S6 immunohistochemistry analysis was unsuccessful due to the lack of adequate tissue samples and was not pursued further.
The biomarkers of interest are pS6 and pAkt. Expression will be classified as low, intermediate, or high based on a composite score of staining intensity and % of tumor cells staining positive. The difference in progression free survival (PFS) time in the "low" to "high" groups is analyzed. PFS is the time from start of treatment to disease progression (PD) or death (estimated by Kaplan Meier method)s. Patients without PD and alive are censored at last date patient is known PD-free. PD is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows: * \>20% increase in the sum of the diameters (SD) of target lesions, referencing the smallest SD on study (including baseline). Must be an increase of \>5 mm. * New lesions or PD of non-target lesions. Must be represent overall disease status change, not a single lesion increase. Patients with PD at the first on-treatment imaging assessment, will remain on study at investigator discretion until later confirmed.
Outcome measures
Outcome data not reported
PRIMARY outcome
Timeframe: Follow-up time was up to 39 months from treatment start date.Population: Twenty-five patients enrolled onto the study between April 2009 and November 2012. One patient became ineligible because of the inability to obtain a pretreatment biopsy sample. A total of 27 tissue samples were successfully obtained from 24 patients, with 3 sets of paired tissues obtained before treatment and while receiving treatment.
Progression free survival (PFS) is defined as the time from start of treatment to disease progression (PD) or death from any cause as estimated by Kaplan Meier methods. Patients who have not progressed and are alive are censored at the date the patient is known to be progression-free. Progression is defined by Response Evaluation Criteria In Solid Tumors Criteria 1.1 (RECIST) as follows: \- \>20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (including baseline if it's the smallest). The sum must also demonstrate an increase of \>5 mm. OR -Appearance of new lesions and/or unequivocal progression of non-target lesions. It must be representative of overall disease status change, not a single lesion increase. For patients with PD at the first on-treatment imaging assessment, patients will be allowed to remain on study until confirmation at the next assessment at investigator discretion if patient is benefiting from treatment.
Outcome measures
| Measure |
Treatment
n=24 Participants
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Median Progression Free Survival
|
3.8 months
Interval 2.4 to 5.4
|
SECONDARY outcome
Timeframe: Evaluated while on treatment. Up to 36 months.The best overall response rate is the percentage of participants achieving complete response (CR) or partial response (PR) as the best response recorded on treatment based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST 1.1) criteria. CR and PR must meet the following lesion criteria without having any new lesions as well: Target Lesion: (CR): Disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to \<10 mm. (PR): At least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Non-Target Lesion: (CR): Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (\<10 mm short axis). Non-CR/Non-Progressive Disease: Persistence of one or more non-target lesion(s) and/or maintenance of tumor marker level above the normal limits. Must have PR in target lesion.
Outcome measures
| Measure |
Treatment
n=24 Participants
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Best Overall Response Rate
|
4.2 percentage of participants
Interval 0.2 to 18.3
|
SECONDARY outcome
Timeframe: Evaluated while on treatment. Up to 36 monthsPopulation: Participants were classified as either "mutations" or "no mutations."
Next generation sequencing was used to identify participants with PI3K-AKT-MTOR mutations. Best overall response rate was analyzed with mutant versus wild-type pathways. Please see Best Overall Response Rate for response definition.
Outcome measures
| Measure |
Treatment
n=24 Participants
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Best Overall Response by PI3K-AKT-MTOR Mutation
Mutation
|
5.6 percentage of participants
|
|
Best Overall Response by PI3K-AKT-MTOR Mutation
No Mutations
|
0 percentage of participants
|
Adverse Events
Treatment
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Treatment
n=24 participants at risk
This is a single-arm study. All patients will receive everolimus.
Everolimus: Tablet form taken orally once a day
|
|---|---|
|
Gastrointestinal disorders
nausea
|
20.8%
5/24 • Number of events 7 • 2 years
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place