Exploratory Study Evaluating Fluorodeoxyglucose - Position Emission Tomography as a Predictive Marker for Therapy With RAD001 in Metastatic Renal Cell Cancer

• Sponsor: University of Chicago (Other)
• Overall Status: Completed
• CT.gov ID: NCT00529802
• Collaborator: Novartis (Industry)
• Enrollment: 60
• Locations: 5
• Arm: 1
• Duration (Months): 34
• Patients Per Site: 12
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

The purpose of this study is to learn if PET scanning can predict the degree of tumor shrinkage with the study drug RAD001 in subjects who have advanced renal cancer.

Condition or Disease	Intervention/Treatment	Phase
Carcinoma, Renal Cell	Drug: RAD001	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 60 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: An Exploratory Study Evaluating FDG-PET as a Predictive Marker for mTOR Directed Therapy With RAD001 in Metastatic Renal Cell Cancer
• Study Start Date: Sep 1, 2007
• Actual Primary Completion Date: Jul 1, 2010
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Everolimus (RAD001) 10mg daily All patients were to receive 10mg everolimus (RAD001) daily.	Drug: RAD001; take 2 tablets of RAD001 once a day by mouth (10 mg per day)

Outcome Measures

Primary Outcome Measures

1. Relative Tumor Size Change Following 8 Weeks of Therapy. [8 weeks]

   The primary objective is to determine whether high SUV uptake on FDG-PET is associated with greater tumor shrinkage. Tumor size is defined as the sum of unidimensional tumor measurements from standard CT imaging calculated according to RECIST criteria. Tumor size is measured at baseline and after eight weeks of therapy. Tumor shrinkage is the relative change (%) in tumor size from baseline.

Secondary Outcome Measures

1. Percent Change in FDG-PETUptake Following 2 Weeks of Therapy [2 weeks]

   The secondary objective was to explore whether an early change in FDG-PET uptake is associated with tumor shrinkage. Change in FDG-PET uptake was calculated using the baseline and 2-week FDG-PET scans.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Metastatic renal cancer refractory to sorafenib or sunitinib therapy

• At least one measurable site of disease according to RECIST criteria that has not been previously irradiated.

• 18 years of age or older

• Minimum of two weeks since any major surgery, completion of radiation, or completion of all prior standard systemic anticancer therapy and adequately recovered from the acute toxicities of any prior therapy.

• World Health Organization (WHO) performance status <= 2

• Adequate bone marrow function

• Adequate liver function

• Adequate creatinine clearance

• Signed informed consent

Exclusion Criteria:

• Prior treatment with any investigational drug within the previous 4 weeks

• Chronic treatment with systemic steroids or another immunosuppressive agent

• Uncontrolled brain or leptomeningeal metastases, including patients who continue to require glucocorticoids for brain or leptomeningeal metastases

• Patients who have a history of another primary malignancy ≤ 3 years, with the exceptions of non-melanoma skin cancer, and carcinoma in situ of uterine cervix

• Patients who have any severe and/or uncontrolled medical conditions or other conditions that could affect their participation in the study

• A known history of HIV seropositivity

• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of RAD001 (e.g., ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection)

• Patients with an active, bleeding diathesis or on oral anti-vitamin K medication

• Women who are pregnant or breast feeding, or women/men able to conceive and unwilling to practice an effective method of birth control from enrollment through 6 months following the end of treatment

• Patients who have received prior treatment with an mTOR inhibitor.

• Patients with a known hypersensitivity to RAD001 (everolimus) or other rapamycins (sirolimus, temsirolimus) or to its excipients

• History of noncompliance to medical regimens

• Patients unwilling to or unable to comply with the protocol

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Chicago	Chicago	Illinois	United States	60637
2	Oncology/Hematology Associates	Peoria	Illinois	United States	61615
3	Beth Israel Deaconess Med Ctr	Boston	Massachusetts	United States	02215
4	Washington University	Saint Louis	Missouri	United States	63110
5	The University of North Carolina at Chapel Hill, Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina	United States	27599

Sponsors and Collaborators

• University of Chicago
• Novartis

Investigators

• Principal Investigator: Walter Stadler, MD, University of Chicago

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• Study results publication available through PMC

Publications

None provided.

• Responsible Party: University of Chicago
• ClinicalTrials.gov Identifier: NCT00529802
• Other Study ID Numbers: 15599B
• First Posted: Sep 14, 2007
• Last Update Posted: Apr 25, 2018
• Last Verified: Mar 1, 2018

• Keywords provided by University of Chicago: metastatic; renal; cell; carcinoma; cancer
• Additional relevant MeSH terms: Carcinoma, Renal Cell; Everolimus

Study Results

Participant Flow

Recruitment Details	A total of 60 patients started trial between December, 2007 and June, 2010 at 5 clinical sites. . A total of 63 patients signed consent, (1 withdrew consent, 2 failed screening)
Pre-assignment Detail	This is a single-arm trial.

Arm/Group Title	Everolimus
Arm/Group Description	All patients were to receive 10mg everolimus (RAD001) daily.
Period Title: Evaluable for Primary Endpoint
STARTED	60
COMPLETED	50
NOT COMPLETED	10
Period Title: Evaluable for Primary Endpoint
STARTED	50
COMPLETED	48
NOT COMPLETED	2

Baseline Characteristics

Arm/Group Title	Everolimus
Arm/Group Description	All patients were to receive 10mg everolimus (RAD001) daily.
Overall Participants	50
Age (years) [Median (Full Range) ]
Median (Full Range) [years]	60
Sex: Female, Male (Count of Participants)
Female	15 30%
Male	35 70%
Tumor Type (participants) [Number]
Clear Cell	36 72%
Papillary Cell	4 8%
Chromophobe	4 8%
Unclassified/Other	6 12%
Average SUVmax (participants) [Number]
Low Uptake (avgSUVmax<=4)	10 20%
High Uptake (avgSUVmax>4)	40 80%

Outcome Measures

1. Primary Outcome

Title	Relative Tumor Size Change Following 8 Weeks of Therapy.
Description	The primary objective is to determine whether high SUV uptake on FDG-PET is associated with greater tumor shrinkage. Tumor size is defined as the sum of unidimensional tumor measurements from standard CT imaging calculated according to RECIST criteria. Tumor size is measured at baseline and after eight weeks of therapy. Tumor shrinkage is the relative change (%) in tumor size from baseline.
Time Frame	8 weeks

Outcome Measure Data

Analysis Population Description

50 patients were evaluable for response and had a baseline FDG-PET scan.

Arm/Group Title	Low Uptake	High Uptake
Arm/Group Description	Low uptake FDG-PET is defined as avgSUVmax<=4; avgSUVmax is the average across all measured lesions of each lesion's maximum SUV (SUV is the "standardized uptake value") .	High uptake of FDG-PET defined as avgSUVmax>4; avgSUVmax is the average across all measured lesions of each lesion's maximum SUV (SUV is the "standardized uptake value") .
Measure Participants	10	40
Mean (Full Range) [Percent change from baseline]	1.4	-0.57

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low Uptake, High Uptake
	Comments	Relative changes in tumor size were log-transformed to satisfy the normality assumption.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.69
	Comments
	Method	t-test, 2 sided
	Comments	Relative changes in tumor size were log-transformed to satisfy the normality assumption for the t-test.
Method of Estimation	Estimation Parameter	Mean Difference (Net)
	Estimated Value	1.9
	Confidence Interval	(2-Sided) 95%; -9.3 to 13.23
	Parameter Dispersion	Type: Value:
	Estimation Comments	Mean difference is the difference between Low and High SUV uptake groups in tumor size percent (%) change from baseline, and is reported on the raw scale. Tumor size changes were log-transformed for the t-test.

2. Secondary Outcome

Title	Percent Change in FDG-PETUptake Following 2 Weeks of Therapy
Description	The secondary objective was to explore whether an early change in FDG-PET uptake is associated with tumor shrinkage. Change in FDG-PET uptake was calculated using the baseline and 2-week FDG-PET scans.
Time Frame	2 weeks

Outcome Measure Data

Analysis Population Description

Patients evaluable for tumor response at 8 weeks who also had both the baseline and 2-week FDG-PET scans.

Arm/Group Title	Patients Evaluable for Secondary Outcome
Arm/Group Description	Patients who had two FDG-PET scans completed, one at baseline and one after 2 weeks of treatment, were evaluable for secondary outcome.
Measure Participants	48
Mean (Full Range) [% change in avgSUVmax at 2 weeks]	-29.7

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Low Uptake
	Comments	The relationship between early changes in SUV uptake (from baseline to 2 weeks) and tumor size changes (from baseline to 8 weeks) were examined using linear regression models. Tumor size change was log-transformed to satisfy the normality assumption.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	0.013
	Comments
	Method	Regression, Linear
	Comments	Tumor size change (outcome variable) was log-transformed to satisfy the normality assumption.
Method of Estimation	Estimation Parameter	Slope
	Estimated Value	0.0028
	Confidence Interval	(2-Sided) 95%; 0.00063 to 0.004997
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .00109
	Estimation Comments	Outcome was log(tumor size at 8 weeks/tumor size at baseline), and the predictor was the early change in aveSUVmax [(aveSUVmax at 2 weeks - aveSUVmax at baseline)/aveSUVmax at baseline] x 100%.

Adverse Events

Adverse Event Reporting Description	These results are based on n=56 patients who were evaluable for toxicity (all patients started treatment but 4 had missing data).
Arm/Group Title	Everolimus
Arm/Group Description	All patients were to receive 10mg everolimus (RAD001) daily. These results are based on n=56 patients who were evaluable for toxicity.
All Cause Mortality
	Everolimus
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Everolimus
	Affected / at Risk (%)	# Events
Total	6/56 (10.7%)
General disorders
Fatigue	1/56 (1.8%)
Injury, poisoning and procedural complications
Fracture	1/56 (1.8%)
Investigations
Creatinine increased	1/56 (1.8%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	1/56 (1.8%)
Pleural effusion	2/56 (3.6%)
Pneumonitis	1/56 (1.8%)
Other (Not Including Serious) Adverse Events
	Everolimus
	Affected / at Risk (%)	# Events
Total	55/56 (98.2%)
Cardiac disorders
Sinus tachycardia	3/56 (5.4%)
Ear and labyrinth disorders
Ear, nose and throat examination abnormal	25/56 (44.6%)
Gastrointestinal disorders
Diarrhea	21/56 (37.5%)
Dry mouth	4/56 (7.1%)
Flatulence	3/56 (5.4%)
Mucositis oral	4/56 (7.1%)
Nausea	21/56 (37.5%)
Vomiting	7/56 (12.5%)
General disorders
Edema limbs	16/56 (28.6%)
Fatigue	40/56 (71.4%)
Fever	8/56 (14.3%)
General symptom	6/56 (10.7%)
Hemorrhage nasal	5/56 (8.9%)
Pain	8/56 (14.3%)
Pain - Other	20/56 (35.7%)
Rigors/chills	4/56 (7.1%)
Taste alteration	8/56 (14.3%)
Infections and infestations
Urinary tract infection	3/56 (5.4%)
Investigations
Hemoglobin decreased	23/56 (41.1%)
Hypercholesterolemia	21/56 (37.5%)
Leukocytes	5/56 (8.9%)
Lymphopenia	6/56 (10.7%)
Platelet count decreased	10/56 (17.9%)
Weight loss	10/56 (17.9%)
Metabolism and nutrition disorders
Hyperglycemia	22/56 (39.3%)
Hyperkalemia	9/56 (16.1%)
Hypertriglyceridemia	24/56 (42.9%)
Hypoalbuminemia	9/56 (16.1%)
Hypocalcemia	3/56 (5.4%)
Hyponatremia	9/56 (16.1%)
Hypophosphatemia	11/56 (19.6%)
Musculoskeletal and connective tissue disorders
Joint pain	3/56 (5.4%)
Pain in extremity	6/56 (10.7%)
Nervous system disorders
Dizziness	5/56 (8.9%)
Headache	10/56 (17.9%)
Neurological disorder NOS	3/56 (5.4%)
Peripheral sensory neuropathy	4/56 (7.1%)
Psychiatric disorders
Insomnia	6/56 (10.7%)
Renal and urinary disorders
Urinary frequency	4/56 (7.1%)
Respiratory, thoracic and mediastinal disorders
Dyspnea	19/56 (33.9%)
Pharyngolaryngeal pain	5/56 (8.9%)
Pneumonitis	7/56 (12.5%)
Pulmonary - Other(specify)	3/56 (5.4%)
Skin and subcutaneous tissue disorders
Dermatology/Skin - Other (Specify)	6/56 (10.7%)
Dry skin	5/56 (8.9%)
Nail changes	5/56 (8.9%)
Pruritus	5/56 (8.9%)
Rash	15/56 (26.8%)
Rash desquamating	10/56 (17.9%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.