Phase I-II Study of Vorinostat, Paclitaxel, and Bevacizumab in Metastatic Breast Cancer

NCT00368875 | Completed Phase 1 Results DMC

• 7 other identifiers: NCI-2012-0301206-05-2917703N01CM62204N01CM62207N01CM62205N01CM62209
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

This phase I/II trial is studying the side effects and best dose of vorinostat when given together with paclitaxel and bevacizumab and to see how well they work in treating patients with metastatic breast cancer and/or breast cancer that has recurred in the chest wall and cannot be removed by surgery. Vorinostat may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as paclitaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some find tumor cells and kill them or carry tumor-killing substances to them. Others interfere with the ability of tumor cells to grow and spread. Bevacizumab may also stop the growth of tumor cells by blocking blood flow to the tumor. Giving vorinostat together with paclitaxel and bevacizumab may kill more tumor cells.

Conditions

Male Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer

Outcome Measures

Primary Outcomes (2)

• Recommended Phase II Dose as Assessed by NCI Common Terminology Criteria for Adverse Events (CTCAE) Version 3.0 (Phase I)

  Dose-limiting toxcities (DLT) were defined as grade 3-4 febrile neutropenia, thrombocytopenia and non-hemtological toxicity attributed to therapy (nausea, vomiting and diarrhea would be considered dose limiting only if not adequately controlled with therapy). Any toxicity occurring during cycle 1 that resulted in dose reduction of vorinostat or paclitaxel or failure to complete all protocol specificed doses in the first cycle was also considered a DLT

  28 days

• Objective Response Rate (CR + PR)

  Estimated and a 95% confidence interval will be estimated via binomial proportions. Per Response Evaluation Criteria in Solid Tumors (RECIST) for target lesions and assessed by CT scan: Complete response (CR): Disappearance of all target lesions; Partial Response (PR): \>=30% decrease in the sum of the longest diameter of target lesions; Overall Response (OR) = CR+PR.

  Up to 12 months

Secondary Outcomes (3)

• Progression-free Survival (PFS),

  From first treatment day until objective or symptomatic progression, assessed up to 12 months

• Time to Treatment Failure (TTF)

  Time from the first treatment day until disease progression or discontinuation of treatment due to toxicity, assessed up to 12 months

• Overall Survival(OS)

  Time from first treatment day until death, assessed up to 12 months

Study Arms (1)

vorinostat, paclitaxel, bevacizumab

EXPERIMENTAL

Vorinostat BID on days 1-3, 8-10, and 15-17, paclitaxel IV over 1 hour on days 2, 9, and 16, bevacizumab IV over 30-90 minutes on days 2 and 16, repeat every 28 days.

Drug: vorinostat; Drug: paclitaxel; Biological: bevacizumab

Interventions

vorinostat DRUG

Given orally

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

vorinostat, paclitaxel, bevacizumab

paclitaxel DRUG

Given IV

Also known as: Anzatax, Asotax, TAX, Taxol

vorinostat, paclitaxel, bevacizumab

bevacizumab BIOLOGICAL

Given IV

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

vorinostat, paclitaxel, bevacizumab

Eligibility Criteria

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

You may qualify if:

• histologically or cytologically confirmed adenocarcinoma of the breast; effective with version 2.2 (1/26/09), only patients with disease that is accessible to biopsy and consent to serial biopsy are eligible
• stage IV disease, locally recurrent inoperable chest wall disease; at least one bidimensional and/or unidimensional, measurable indicator lesion must be present (patients with only non-measurable disease are eligible for the phase I trial only); all sites of disease should be noted and followed
• ECOG performance status =\< 1 (Karnofsky \>= 70%)
• Absolute neutrophil count \>= 1,500/ul
• Platelets \>= 100,000/ul
• Total bilirubin within normal institutional limits
• AST(SGOT)/ALT(SGPT) =\< 2.5 x institutional upper limit of normal
• PTT and either INR or PT \< 1.5 x normal
• Creatinine within normal institutional limits OR creatinine clearance \>= mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
• Urine protein should be screened by urine analysis for Urine Protein Creatinine (UPC) ratio; for UPC ratio \> 0.5, 24-hour urine protein should be obtained and the level should be \< 1000 mg for patient enrollment;
• LVEF must be at or above the lower institutional limit of the normal range (on MUGA or Echo obtained within 12 weeks of registration, or within 4 weeks of prior Herceptin)
• Not pregnant/lactating

You may not qualify if:

• chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
• may not be receiving any other investigational agents.
• history of allergic reactions attributed to compounds of similar chemical or biologic composition to vorinostat or other agents used in the study (e.g., paclitaxel, bevacizumab, quinolones)
• uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

Montefiore Medical Center

The Bronx, New York, 10467-2490, United States

Location

Related Publications (1)

• Ramaswamy B, Fiskus W, Cohen B, Pellegrino C, Hershman DL, Chuang E, Luu T, Somlo G, Goetz M, Swaby R, Shapiro CL, Stearns V, Christos P, Espinoza-Delgado I, Bhalla K, Sparano JA. Phase I-II study of vorinostat plus paclitaxel and bevacizumab in metastatic breast cancer: evidence for vorinostat-induced tubulin acetylation and Hsp90 inhibition in vivo. Breast Cancer Res Treat. 2012 Apr;132(3):1063-72. doi: 10.1007/s10549-011-1928-x. Epub 2011 Dec 27.

  PMID: 22200869 RESULT

MeSH Terms

Conditions

Breast Neoplasms, Male; Breast Neoplasms

Interventions

Vorinostat; Paclitaxel; Taxes; Bevacizumab

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Anilides; Amides; Organic Chemicals; Aniline Compounds; Amines; Hydroxamic Acids; Hydroxylamines; Hydroxy Acids; Carboxylic Acids; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes; Economics; Health Care Economics and Organizations; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Results Point of Contact

• Title: NYCC Regulatory Coordinator
• Organization: Montefiore Medical Center - New York

sforde@montefiore.org

718-379-6862

Study Officials

• Joseph Sparano

  Montefiore Medical 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: August 24, 2006
• First Posted: August 29, 2006
• Study Start: July 1, 2006
• Primary Completion: December 1, 2011
• Study Completion: December 1, 2011
• Last Updated: November 5, 2015
• Results First Posted: November 5, 2015

Record last verified: 2014-03

Locations

US (1)