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

NCT00324870 | Completed Phase 1 Results

• 12 other identifiers: NCI-2009-00093NA 00001107NCI-6884JHOC-J0570CDR00004678006884JHOC-00001107J0570IRB #NA 00001107, SKCCC J0570P30CA006973U01CA062491U01CA070095
• Study Type: interventional
• Target: 37
• Locations: 1 country
• Sites: 3

Brief 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. 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.

Conditions

Clear Cell Renal Cell Carcinoma; Recurrent Renal Cell Cancer; Stage III Renal Cell Cancer; Stage IV Renal Cell Cancer

Outcome Measures

Primary Outcomes (1)

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

  Estimated by Kaplan-Meier method

  At 6 months

Other Outcomes (2)

• Maximum Tolerated Dose

  18 months from first patient dosing

• Clinical Response Rate of SAHA and Bevacizumab

  7 years

Study Arms (1)

Arm I

EXPERIMENTAL

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.

Drug: vorinostat; Drug: bevacizumab

Interventions

vorinostat DRUG

Given orally

Also known as: L-001079038, SAHA, suberoylanilide hydroxamic acid, Zolinza

Arm I

bevacizumab DRUG

Given IV

Also known as: anti-VEGF humanized monoclonal antibody, anti-VEGF monoclonal antibody, Avastin, rhuMAb VEGF

Arm I

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (3)

Johns Hopkins University/Sidney Kimmel Cancer Center

Baltimore, Maryland, 21287, United States

Location

Peninsula Oncology and Hematology PA

Salisbury, Maryland, 21801, United States

Location

University of Wisconsin Hospital and Clinics

Madison, Wisconsin, 53792, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

Vorinostat; Bevacizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: Michael Carducci, MD
• Organization: Johns Hopkins University

carducci@jhmi.edu

410-614-6337

Study Officials

• Michael Carducci

  Johns Hopkins University/Sidney Kimmel Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 10, 2006
• First Posted: May 11, 2006
• Study Start: February 1, 2006
• Primary Completion: June 1, 2013
• Study Completion: November 1, 2013
• Last Updated: January 13, 2016
• Results First Posted: September 9, 2015

Record last verified: 2013-10

Locations

US (3)