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Clear Cell Renal Cell CarcinomaPhase 1/2NCT00324870

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

A Phase 1/2 study testing vorinostat and bevacizumab in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial summary

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. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
vorinostat and bevacizumab
Could I receive a placebo?
No, everyone receives an active treatment
How many people
37 participants
Where
3 sitesUnited States
Study dates
Feb 2006to Nov 2013
Phase
Phase 1/2
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • No known CNS metastasis
  • ECOG performance status 0-2
  • Life expectancy > 6 months
  • LVEF ≥ 45%
  • Absolute neutrophil count ≥ 1,500/mm3
  • Platelet count ≥ 100,000/mm3
Show all 54Show fewer
  • 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
  • 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 investigational agents
  • Concurrent stable-dose prophylactic anticoagulation (i.e., warfarin or low molecular weight heparin) allowed provided requirements for INR are met
  • Histologically confirmed renal cell carcinoma, clear cell component, unresectable or metastatic disease (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
  • WBC ≥ 3,000/mm^3

Who cannot join

None listed.

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Johns Hopkins University/Sidney Kimmel Cancer Center

    Baltimore, Maryland, 21287

  • University of Wisconsin Hospital and Clinics

    Madison, Wisconsin, 53792

  • Peninsula Oncology and Hematology PA

    Salisbury, Maryland, 21801

Other trials in United States

About this study

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

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. 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.

Read the detailed description

PRIMARY OBJECTIVES:

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

SECONDARY OBJECTIVES:

  1. Determine the toxicity of this regimen in these patients. (Phase II) II. Determine time to progression and duration of progression-free and overall survival in patients treated with this regimen. (Phase II) III. Determine the pharmacodynamic effects in peripheral blood mononuclear cells and tumors before and after treatment with this regimen in these patients. (Phase II) IV. Determine the antiproliferative and apoptotic effects of this regimen in these patients. (Phase II) V. Determine the antiangiogenic effects of this regimen in these patients. (Phase II) VI. 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.

Being tested
vorinostat, bevacizumab
Medical subject headings
Carcinoma, Renal Cell

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • vorinostatDrug

    Also called L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

    Given orally

  • bevacizumabDrug

    Also called anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

    Given IV

Study groups in NCT00324870
Study groupRoleWhat they receive
Arm IExperimentalPhase 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.
Receives: Drug: vorinostat; Drug: bevacizumab

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) (Phase II)

    Estimated by Kaplan-Meier method

    Measured: At 6 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted11 May 2006 (estimated)
  2. Study startFeb 2006
  3. Primary completionJun 2013
  4. Study completionNov 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
37 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00324870
Sponsor's protocol ID
NCI-2009-00093
Other IDs
NCI-2009-00093, NA 00001107, NCI-6884, JHOC-J0570, CDR0000467800, 6884, JHOC-00001107, J0570
Status last verified
Oct 2013
First submitted
10 May 2006
Last updated
13 Jan 2016

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing vorinostat and bevacizumab in people with Clear Cell Renal Cell Carcinoma and Recurrent Renal Cell Cancer, run by National Cancer Institute (NCI) at 3 sites in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 54 inclusion and 0 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 13 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 3 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 9 Sep 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Progression-free Survival Assessed by Response Evaluation Criteria for Solid Tumors (RECIST) (Phase II) (time frame: At 6 months). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT00324870.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Jan 2016.

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