Vorinostat in Treating Patients With Kidney Cancer

• Sponsor: National Cancer Institute (NCI) (NIH)
• Overall Status: Completed
• CT.gov ID: NCT00278395
• Collaborator: (none)
• Enrollment: 14
• Locations: 2
• Arm: 1
• Duration (Months): 52
• Patients Per Site: 7
• Patients Per Site Per Month: 0.1

Study Details

Study Description

Brief Summary

This phase II trial is studying how well vorinostat works in treating patients with advanced kidney cancer. Drugs used in chemotherapy, such as vorinostat, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Vorinostat may also stop the growth of tumor cells by blocking blood flow to the tumor.

Condition or Disease	Intervention/Treatment	Phase
Recurrent Renal Cell Carcinoma; Stage IV Renal Cell Cancer	Drug: Vorinostat	Phase 2

Detailed Description

PRIMARY OBJECTIVES:

1. Determine the antitumor activity of vorinostat (SAHA), in terms of objective response and progression rate, in patients with advanced renal cell carcinoma.

SECONDARY OBJECTIVES:

1. Evaluate the safety and tolerability of this drug, in terms of toxicity profile, in these patients.

2. Evaluate overall survival, progression-free survival, and survival rate at 12 months in patients treated with this drug.

3. Correlate changes in biologic measurements with outcomes of patients treated with this drug.

OUTLINE: This is an open-label, multicenter study.

Patients receive oral vorinostat (SAHA) twice daily on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may have the option of continuing treatment beyond 52 weeks at the discretion of the investigator.

After completion of study treatment, patients are followed within 1 month and then approximately every 2 months thereafter.

Study Design

• Study Type: Interventional
• Actual Enrollment: 14 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase II, Pharmacokinetic and Biologic Correlative Study of Suberoylanilide Hydroxamic Acid (SAHA) in Patients With Advanced Renal Cell Carcinoma (RCC)
• Study Start Date: Oct 1, 2005
• Actual Primary Completion Date: Feb 1, 2010
• Actual Study Completion Date: Feb 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm I Patients receive oral vorinostat (SAHA) twice daily on days 1-3, 8-10, 15-17, and 22-24. Courses repeat every 28 days for up to 52 weeks in the absence of disease progression or unacceptable toxicity. Patients may have the option of continuing treatment beyond 52 weeks at the discretion of the investigator.	Drug: Vorinostat; Given orally; Other Names: L-001079038 SAHA Suberanilohydroxamic Acid Suberoylanilide Hydroxamic Acid Zolinza

Outcome Measures

Primary Outcome Measures

1. Objective Response [1 year]

   Objective response is measured using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST criteria. Complete Response (CR) - Disappearance of all target lesions, Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.

Secondary Outcome Measures

1. Progression-free Survival [1 year]

2. Overall Survival (OS) and Median OS [1 year]

3. Safety and Tolerability [1 year]

Eligibility Criteria

Criteria

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

Inclusion Criteria:

• Histologically or cytologically confirmed diagnosis of advanced renal cell carcinoma that is either metastatic or inoperable

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

• Disease is recurrent or refractory to interleukin-2 (IL-2) or interferon-based therapy OR new diagnosis in previously untreated patients who are not appropriate candidates to receive IL-2 based treatment

• Patients who have failed up to 4 lines of prior immunotherapy or biological therapy allowed

• No known brain metastases or leptomeningeal disease

• Stable brain metastases or curatively resected brain metastases without neurologic dysfunction for ≥ 6 months allowed

• ECOG performance status 0-2 OR Karnofsky 70-100%

• Life expectancy ≥ 12 weeks

• Absolute neutrophil count ≥ 1,500/mm^3

• Platelet count ≥ 100,000/mm^3

• Hemoglobin ≥ 9.0 g/dL

• Serum creatinine ≤ 1.5 times upper limit of normal (ULN) OR creatinine clearance > 50 mL/min

• Total bilirubin within normal limits

• AST/ALT ≤ 2.5 times ULN (≤ 5 times ULN if liver metastasis is present)

• No history of active malignancy (other than renal cell carcinoma) within the past 3 years other than nonmelanomatous skin cancer, in situ breast cancer, or in situ cervical cancer

• No history of allergic reactions to compounds of similar chemical or biological composition to vorinostat (SAHA)

• No uncontrolled concurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia

• No psychiatric illness or social situation that would preclude study compliance

• No clinically significant hypercalcemia

• No significant traumatic injury within the past 21 days

• Not pregnant or nursing

• Negative pregnancy test

• Fertile patients must use effective contraception

• No gastrointestinal disease resulting in an inability to take oral medication

• No requirement for IV alimentation

• No active peptic ulcer disease

• Recovered from prior therapy

• Prior nephrectomy or resection of metastatic lesions allowed provided full surgical recovery has occurred

• No chemotherapy within the past 4 weeks (6 weeks for nitrosoureas or mitomycin)

• No radiotherapy within the past 4 weeks

• No valproic acid for at least 2 weeks prior to study enrollment

• No prior surgical procedures affecting absorption

• No major surgery within the past 21 days

• No concurrent antiretroviral therapy for HIV-positive patients

• No other concurrent investigational agents

• No other concurrent anticancer therapy

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Cancer Therapy and Research Center at The UT Health Science Center at San Antonio	San Antonio	Texas	United States	78229
2	Institute for Drug Development	San Antonio	Texas	United States	78245

Sponsors and Collaborators

• National Cancer Institute (NCI)

Investigators

• Principal Investigator: John Sarantopoulos, Institute for Drug Development

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: National Cancer Institute (NCI)
• ClinicalTrials.gov Identifier: NCT00278395
• Other Study ID Numbers: NCI-2009-00087; NCI-2009-00087; CDR0000456500; #04-10; 6825; U01CA069853
• First Posted: Jan 18, 2006
• Last Update Posted: Nov 14, 2017
• Last Verified: Oct 1, 2017

• Additional relevant MeSH terms: Carcinoma; Carcinoma, Renal Cell; Vorinostat

Study Results

Participant Flow

Recruitment Details	Open to recruitment on 12/5/2005, closed to recruitment on 3/3/09 at The University of Texas Health Science Center San Antonio at Cancer and Therapy Research Center

Arm/Group Title	Vorinostat
Arm/Group Description	The oral dose of vorinostat capsules was 300 mg two times a day for 3 consecutive days every week for 4 weeks, which constitutes on cycle of treatment. Treatment will be administered on an outpatient basis.
Period Title: Overall Study
STARTED	14
COMPLETED	11
NOT COMPLETED	3

Baseline Characteristics

Arm/Group Title	Vorinostat
Arm/Group Description	The dose of vorinostat was 300 mg two times a day on the first 3 days of every week on a 4-week cycle.
Overall Participants	14
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	12 85.7%
>=65 years	2 14.3%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60 (2)
Sex: Female, Male (Count of Participants)
Female	5 35.7%
Male	9 64.3%
Region of Enrollment (participants) [Number]
United States	14 100%

Outcome Measures

1. Primary Outcome

Title	Objective Response
Description	Objective response is measured using the international criteria proposed by the Response Evaluation Criteria in Solid Tumors (RECIST) Committee. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in RECIST criteria. Complete Response (CR) - Disappearance of all target lesions, Partial Response (PR) - at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, Progressive Disease (PD) - At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions, Stable Disease (SD) - Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started.
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

The overall duration of response will be estimated using the Kaplan-Meier method for all patients who presented with an objective response.

Arm/Group Title	Vorinostat
Arm/Group Description	The dose of Vorinostat was 300 mg BID on the first 3 days of every week on a 4-week cycle. Dose reduction was allowed for adverse events (AE). Treatment was planned until disease progression (PD), death, unacceptable toxicity, or consent withdrawal.
Measure Participants	11
Best Objective Response Rate (ORR)	4 28.6%
Progressive Disease	7 50%

2. Secondary Outcome

Title	Progression-free Survival
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Progression Free Survival
Arm/Group Description	No measurement reported
Measure Participants	0

3. Secondary Outcome

Title	Overall Survival (OS) and Median OS
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Overall Survival (OS) and Median OS
Arm/Group Description	No measurement reported
Measure Participants	0

4. Secondary Outcome

Title	Safety and Tolerability
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

Data were not collected

Arm/Group Title	Safety and Tolerability
Arm/Group Description	No participants measured
Measure Participants	0

Adverse Events

Arm/Group Title	Vorinostat
Arm/Group Description	The dose of vorinostat was 300 mg two times a day on the first 3 days of every week on a 4-week cycle.
All Cause Mortality
	Vorinostat
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Vorinostat
	Affected / at Risk (%)	# Events
Total	1/14 (7.1%)
Cardiac disorders
Congestive Heart Failure	1/14 (7.1%)	1
Respiratory, thoracic and mediastinal disorders
Shortness of Breath	1/14 (7.1%)	1
Other (Not Including Serious) Adverse Events
	Vorinostat
	Affected / at Risk (%)	# Events
Total	7/14 (50%)
Blood and lymphatic system disorders
Fatigue	7/14 (50%)	7
Gastrointestinal disorders
Nausea	7/14 (50%)	7
Weight loss	6/14 (42.9%)	6
Diarrhea	4/14 (28.6%)	4
Vomiting	4/14 (28.6%)	4

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.