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Vorinostat and Bevacizumab in Treating Patients With Unresectable or Metastatic Kidney Cancer
This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), July 2009
First Received: May 10, 2006   Last Updated: July 7, 2009   History of Changes
Sponsors and Collaborators: Sidney Kimmel Comprehensive Cancer Center
National Cancer Institute (NCI)
Information provided by: National Cancer Institute (NCI)
ClinicalTrials.gov Identifier: NCT00324870
  Purpose

RATIONALE: Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.

Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Bevacizumab may also stop the growth of kidney cancer by blocking blood flow to the tumor. Giving vorinostat together with bevacizumab may kill more tumor cells.

PURPOSE: This phase I/II trial is studying the side effects and best dose of vorinostat when given together with bevacizumab and to see how well they work in treating patients with unresectable or metastatic kidney cancer.


Condition Intervention Phase
Kidney Cancer
Biological: bevacizumab
Drug: vorinostat
Phase I
Phase II

Study Type: Interventional
Study Design: Treatment
Official Title: Phase I/II Study of Suberoylanilide Hydroxamic Acid (SAHA) in Combination With the VEGF Inhibitor Bevacizumab in Patients With Metastatic Renal Cell Carcinoma

Resource links provided by NLM:


Further study details as provided by National Cancer Institute (NCI):

Primary Outcome Measures:
  • Maximum tolerated dose (phase I) [ Designated as safety issue: Yes ]
  • Progression-free survival at 6 months (phase II) [ Designated as safety issue: No ]
  • Response rate (partial or complete response) [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Toxicity [ Designated as safety issue: Yes ]
  • Time to progression, disease-free survival, and overall survival as measured by Kaplan-Meier method [ Designated as safety issue: No ]
  • Pharmacodynamic effects in peripheral blood mononuclear cells at baseline and after completion of study treatment [ Designated as safety issue: No ]
  • Antiproliferative and apoptotic effects [ Designated as safety issue: No ]
  • Antiangiogenic effects [ Designated as safety issue: No ]
  • Modulation of tumor metabolism and tumor blood flow as measured by fluorine-18-labeled deoxyglucose (FDG) and 15 O water positron-emission tomography (PET) scan [ Designated as safety issue: No ]

Estimated Enrollment: 42
Study Start Date: February 2006
Estimated Primary Completion Date: August 2007 (Final data collection date for primary outcome measure)
Detailed Description:

OBJECTIVES:

Primary

  • Determine the safety and tolerability of vorinostat (SAHA) in combination with bevacizumab in patients with unresectable or metastatic renal cell carcinoma. (Phase I)
  • Determine the recommended dosing in patients treated with this regimen. (Phase I)
  • Determine the proportion of patients who are progression-free at 6 months after receiving this regimen.

(Phase II)

  • Determine the clinical response rate in patients treated with this regimen. (Phase II)

Secondary

  • Determine the toxicity of this regimen in these patients. (Phase II)
  • Determine time to progression and duration of progression-free and overall survival in patients treated with this regimen. (Phase II)
  • Determine the pharmacodynamic effects in peripheral blood mononuclear cells and tumors before and after treatment with this regimen in these patients. (Phase II)
  • Determine the antiproliferative and apoptotic effects of this regimen in these patients. (Phase II)
  • Determine the antiangiogenic effects of this regimen in these patients. (Phase II)
  • Determine the modulation of tumor metabolism and tumor blood flow in patients treated with this regimen.

(Phase II)

OUTLINE: This is a phase I, dose-escalation study of vorinostat (SAHA) followed by a phase II study.

  • 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.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

PROJECTED ACCRUAL: A total of 42 patients will be accrued for this study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

DISEASE CHARACTERISTICS:

  • Histologically confirmed renal cell carcinoma

    • Clear cell component
    • Unresectable or metastatic disease* NOTE: *Patients with a primary tumor in place who are eligible for surgery are strongly encouraged to undergo a nephrectomy prior to study entry to increase potential survival
  • Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR

    • 10 mm with spiral CT scan
  • The following histologies are not allowed:

    • Papillary, sarcomatoid carcinoma
    • Chromophobe carcinoma
    • Oncocytoma
    • Collecting duct tumor
    • Transitional cell carcinoma
  • No known CNS metastasis

PATIENT CHARACTERISTICS:

  • ECOG performance status 0-2
  • Life expectancy > 6 months
  • LVEF ≥ 45%
  • WBC ≥ 3,000/mm^3
  • Absolute neutrophil count ≥ 1,500/mm^3
  • Platelet count ≥ 100,000/mm^3
  • Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
  • AST/ALT ≤ 2.5 times ULN
  • Creatinine ≤ 1.5 times ULN OR creatinine clearance ≥ 50 mL/min
  • PT/INR ≤ 1.5
  • Urine protein < 1+ by urinalysis OR < 1 g by 24-hour urine collection
  • Not pregnant
  • No nursing during and for 6 months after completion of study treatment
  • Negative pregnancy test
  • Fertile patients must use effective contraception for 2 weeks prior, during, and for 6 months after completion of study treatment
  • No other currently active malignancy defined as > 30% risk of relapse upon completion of anticancer therapy, except nonmelanoma skin cancer
  • No history of allergic reaction attributed to compounds of similar chemical or biologic composition to vorinostat (SAHA)
  • No hypersensitivity to Chinese hamster ovary cell products or other recombinant human antibodies
  • No evidence of bleeding diathesis or coagulopathy
  • No active bleeding or pathological conditions that carry high risk of bleeding (i.e., tumor involving major vessels or known varices)
  • No ongoing, active infection
  • No New York Heart Association class II-IV congestive heart failure
  • No angina pectoris requiring nitrate therapy
  • No cardiac arrhythmia
  • No myocardial infarction within the past 6 months
  • No history of cerebrovascular accident within the past 6 months
  • No uncontrolled hypertension (defined as systolic blood pressure (BP) > 160 mm Hg and/or diastolic BP > 90 mm Hg on medication)
  • No history of peripheral vascular disease
  • No psychiatric illness or social situation that would preclude study compliance
  • No other uncontrolled illness
  • No serious nonhealing wound, ulcer, or bone fracture
  • No history of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 28 days
  • No significant traumatic injury in the past 28 days

PRIOR CONCURRENT THERAPY:

  • At least 4 weeks since prior major surgery or open biopsy
  • More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
  • More than 4 weeks since prior radiotherapy
  • At least 2 weeks since prior tyrosine kinase inhibitor
  • Prior palliative radiotherapy to metastatic lesions allowed provided ≥ 1 measurable and/or evaluable lesion has not been irradiated
  • No more than 2 prior systemic treatments for metastatic disease, including immunotherapy, receptor tyrosine kinase inhibitor therapy, chemotherapy, or investigational therapy
  • No prior therapy with bevacizumab, vascular endothelial growth factor-trap, or histone deacetylase inhibitors, including valproic acid
  • No core biopsy within 1 week prior to day 1 of study treatment
  • No planned major surgery during study treatment
  • No concurrent combination antiretroviral therapy for HIV-positive patients
  • No other concurrent anticancer agents or therapies
  • No other concurrent investigational agents
  • Concurrent stable-dose prophylactic anticoagulation (i.e., warfarin or low molecular weight heparin) allowed provided requirements for INR are met
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00324870

Locations
United States, Maryland
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins Recruiting
Baltimore, Maryland, United States, 21231-2410
Contact: Clinical Trials Office - Sidney Kimmel Comprehensive Cancer Ce     410-955-8804     jhcccro@jhmi.edu    
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center
Investigators
Principal Investigator: Michael A. Carducci, MD Sidney Kimmel Comprehensive Cancer Center
  More Information

Additional Information:
Publications:
Pili R, Wilky B, Salumbides B, et al.: Phase I/II trial of the histone deacetylase inhibitor vorinostat in combination with bevacizumab in patients with renal cell carcinoma: phase I safety and pharmacokinetic/pharmacodynamic results. [Abstract] American Society of Clinical Oncology 2008 Genitourinary Cancers Symposium, Feb 14-16, 2008, San Francisco, CA. A-371, 2008.

Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins ( Michael A. Carducci )
Study ID Numbers: CDR0000467800, JHOC-J0570, JHOC-00001107, NCI-6884
Study First Received: May 10, 2006
Last Updated: July 7, 2009
ClinicalTrials.gov Identifier: NCT00324870     History of Changes
Health Authority: Unspecified

Keywords provided by National Cancer Institute (NCI):
clear cell renal cell carcinoma
stage III renal cell cancer
stage IV renal cell cancer
recurrent renal cell cancer

Study placed in the following topic categories:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Urinary Tract Neoplasm
Kidney Cancer
Vorinostat
Urogenital Neoplasms
Bevacizumab
Urologic Neoplasms
Angiogenesis Inhibitors
Recurrence
Carcinoma
Renal Cancer
Urologic Diseases
Analgesics, Non-Narcotic
Kidney Neoplasms
Carcinoma, Renal Cell
Clear Cell Renal Cell Carcinoma
Anti-Inflammatory Agents, Non-Steroidal
Peripheral Nervous System Agents
Analgesics
Kidney Diseases
Antirheumatic Agents
Adenocarcinoma
Neoplasms, Glandular and Epithelial

Additional relevant MeSH terms:
Anticarcinogenic Agents
Anti-Inflammatory Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Physiological Effects of Drugs
Urogenital Neoplasms
Bevacizumab
Urologic Neoplasms
Neoplasms by Site
Urologic Diseases
Kidney Neoplasms
Sensory System Agents
Therapeutic Uses
Anti-Inflammatory Agents, Non-Steroidal
Growth Inhibitors
Angiogenesis Modulating Agents
Kidney Diseases
Analgesics
Neoplasms by Histologic Type
Growth Substances
Vorinostat
Enzyme Inhibitors
Angiogenesis Inhibitors
Protective Agents
Pharmacologic Actions
Carcinoma
Neoplasms
Analgesics, Non-Narcotic
Carcinoma, Renal Cell
Peripheral Nervous System Agents

ClinicalTrials.gov processed this record on September 01, 2009