Vorinostat and Bevacizumab in Treating Patients With Unresectable or Metastatic Kidney Cancer

• ClinicalTrials.gov Identifier: NCT00324870
• Recruitment Status: Completed
• First Posted: May 11, 2006
• Results First Posted: September 9, 2015
• Last Update Posted: January 13, 2016
• Sponsor: National Cancer Institute (NCI)
• Information provided by (Responsible Party): National Cancer Institute (NCI)

• Study Type: Interventional
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Conditions: Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer
• Interventions: Drug: vorinostat; Drug: bevacizumab
• Enrollment: 37

Participant Flow

Recruitment Details
Pre-assignment Details

Arm/Group Title	Arm I
Arm/Group Description	Phase I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I. vorinostat: Given orally bevacizumab: Given IV
Period Title: Overall Study
Started	37
Completed	37
Not Completed	0

Baseline Characteristics

Arm/Group Title		Arm I
Arm/Group Description		Phase I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I. vorinostat: Given orally bevacizumab: Given IV
Overall Number of Baseline Participants		37
Baseline Analysis Population Description		[Not Specified]
Age, Continuous; Median (Full Range); Unit of measure: Years
	Number Analyzed	37 participants
		64; (34 to 82)
Age, Categorical; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	<=18 years	0 0.0%
	Between 18 and 65 years	20 54.1%
	>=65 years	17 45.9%
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	37 participants
	Female	6 16.2%
	Male	31 83.8%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	37 participants
		37

Outcome Measures

1. Primary Outcome

Title	Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) (Phase II)
Description	Estimated by Kaplan-Meier method
Time Frame	At 6 months

Outcome Measure Data

Analysis Population Description

Progression free survival was summarized for the entire sample (n=37). The median survival times and 6-month survival rates are estim. based on the KP curve,w/ corresp. 95% confidence intervals using the log-log method. Conducted in SAS v9.3(Cary, NC). Progr.free survival time is calc. from date of first tx until date of progres./death or last fu.

Arm/Group Title	Arm I
Arm/Group Description:	Phase I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I. vorinostat: Given orally bevacizumab: Given IV
Overall Number of Participants Analyzed	37
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percent
	48.6; (32 to 63.4)

2. Other Pre-specified Outcome

Title	Maximum Tolerated Dose
Description	Determine the maximum tolerated dose of SAHA
Time Frame	18 months from first patient dosing

Outcome Measure Data Not Reported

3. Other Pre-specified Outcome

Title	Clinical Response Rate of SAHA and Bevacizumab
Description	To determine the clinical response rate of SAHA and Bevacizumab in patients with metastatic renal cell carcinoma.
Time Frame	7 years

Outcome Measure Data Not Reported

Adverse Events

Time Frame	7 years
Adverse Event Reporting Description	Adverse events were assessed through a regular investigator assessment
Arm/Group Title	Arm I
Arm/Group Description	Phase I: Patients receive oral SAHA twice daily on days 1-14 and bevacizumab IV over 30-90 minutes on day 1. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of SAHA until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. An additional 6 patients are treated at the MTD. Phase II: Patients receive SAHA at the MTD determined in phase I and bevacizumab as in phase I. vorinostat: Given orally bevacizumab: Given IV
All-Cause Mortality
	Arm I
	Affected / at Risk (%)
Total	--/--
Serious Adverse Events
	Arm I
	Affected / at Risk (%)	# Events
Total	3/37 (8.11%)
Blood and lymphatic system disorders
thrombocytopenia † 1	1/37 (2.70%)	1
Nervous system disorders
dizziness † 1	1/37 (2.70%)	1
Respiratory, thoracic and mediastinal disorders
pulmonary embolism † 1	1/37 (2.70%)	1
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Arm I
	Affected / at Risk (%)	# Events
Total	22/37 (59.46%)
Gastrointestinal disorders
nausea † 1	17/37 (45.95%)	17
anorexia † 1	16/37 (43.24%)	16
diarrhea † 1	13/37 (35.14%)	13
Hepatobiliary disorders
elevated creatinine † 1	13/37 (35.14%)	13
Nervous system disorders
fatigue † 1	22/37 (59.46%)	22
† Indicates events were collected by systematic assessment; 1 Term from vocabulary, MedDRA (10.0)

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

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

There IS an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Michael Carducci, MD
• Organization: Johns Hopkins University
• Phone: 410-614-6337
• EMail: carducci@jhmi.edu

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00324870
• Other Study ID Numbers: NCI-2009-00093; NCI-2009-00093 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) ); NA 00001107; NCI-6884; JHOC-J0570; CDR0000467800; 6884; JHOC-00001107; J0570; IRB #NA 00001107, SKCCC J0570 ( Other Identifier: Johns Hopkins University/Sidney Kimmel Cancer Center ); 6884 ( Other Identifier: CTEP ); P30CA006973 ( U.S. NIH Grant/Contract ); U01CA062491 ( U.S. NIH Grant/Contract ); U01CA070095 ( U.S. NIH Grant/Contract )
• First Submitted: May 10, 2006
• First Posted: May 11, 2006
• Results First Submitted: August 10, 2015
• Results First Posted: September 9, 2015
• Last Update Posted: January 13, 2016