Carboplatin, Paclitaxel, Bevacizumab and Vorinostat for Patients With Advanced Non-Small Cell Lung Cancer - Full Text View

Sponsor:	Penn State University
Information provided by:	Penn State University
ClinicalTrials.gov Identifier:	NCT00702572

Purpose

The primary objective of the study is to establish the phase II recommended dose of Vorinostat when administered in combination with the regimen of carboplatin, paclitaxel and bevacizumab for patients with previously untreated advanced non-small cell lunc cancer.

Condition	Intervention	Phase
Non-small Cell Lung Cancer	Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel	Phase I

Study Type:	Interventional
Study Design:	Allocation: Non-Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Phase I Study of Carboplatin, Paclitaxel, Bevacizumab and Vorinostat for Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Paclitaxel Carboplatin Suberoylanilide hydroxamic acid Bevacizumab

U.S. FDA Resources

Further study details as provided by Penn State University:

Primary Outcome Measures:

Establish the phase II recommended dose (P2RD) of Vorinostat when administered in combination with the regimen of carboplatin, paclitaxel and bevacizumab for patients with previously untreated advanced non-small cell lung cancer. [ Time Frame: An average of 2 years ] [ Designated as safety issue: No ]
Participants will be followed for survival, an expected average of two years.

Secondary Outcome Measures:

Evaluate safety profile of 4-drug regimen. Obtain preliminary evidence regarding anti-cancer activity of the regimen. Understand mechanistic aspects of drug effect by conducting correlative science studies on peripheral blood and archived tumor tissue. [ Time Frame: Average of 2 years ] [ Designated as safety issue: Yes ]
Participants will be followed for survival, an expected average of 2 years.

Estimated Enrollment:	25
Study Start Date:	April 2008
Estimated Study Completion Date:	May 2013
Estimated Primary Completion Date:	May 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Phase I dose escalating scheme	Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel This dose escalating phase will enroll sequential cohorts of 3-6 patients to be entered at the following dose levels: Level -1: Days 1-14, Vorinostat 100 mg po QD; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 175 mg/m2. Level 1: Days 1-14, Vorinostat 200 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Level 2: Days 1-14, Vorinostat 300 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Level 3: Days 1-14, Vorinostat 400 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Treatment cycles will be repeated every 3 weeks. The highest dose level which <2 out of 5 patients experience dose limiting toxicity will be defined as the recommended phase II dose. Other Name: SAHA
Experimental: 2 Phase 2 will evaluate the toxicities and safety profile of the 4-drug regimen.	Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel Once the recommended phase II dose has been established from Phase I, 12 additional patients will be treated to evaluate the toxicities and safety profile of the 4-drug regimen. Other Name: SAHA

Arms

Assigned Interventions

Experimental: 1

Phase I dose escalating scheme

Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel

This dose escalating phase will enroll sequential cohorts of 3-6 patients to be entered at the following dose levels: Level -1: Days 1-14, Vorinostat 100 mg po QD; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 175 mg/m2. Level 1: Days 1-14, Vorinostat 200 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Level 2: Days 1-14, Vorinostat 300 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Level 3: Days 1-14, Vorinostat 400 mg po QD days 1-14; Day 3, Bevacizumab 15 mg/kg; Carboplatin 6 AUC; Paclitaxel 200 mg/m2. Treatment cycles will be repeated every 3 weeks. The highest dose level which <2 out of 5 patients experience dose limiting toxicity will be defined as the recommended phase II dose.

Other Name: SAHA

Experimental: 2

Phase 2 will evaluate the toxicities and safety profile of the 4-drug regimen.

Drug: Vorinostat, Bevacizumab, Carboplatin, Paclitaxel

Once the recommended phase II dose has been established from Phase I, 12 additional patients will be treated to evaluate the toxicities and safety profile of the 4-drug regimen.

Other Name: SAHA

Detailed Description:

Since the regimen of bevacizumab, carboplatin and paclitaxel has become a standard regimen for the treatment of advanced non-squamous NSCLC, new studies in this patient population will have to include this as a reference arm. Addition of a fourth anti-cancer agent has now become the new strategy to improve the outcome for advanced non-squamous NSCLC. Since the regimen of Vorinostat, Carboplatin and Paclitaxel is already in advanced stage of development it is important to study the safety and tolerability of Vorinostat in combination with the three-drug regimen of Bevacizumab, Carboplatin and Paclitaxel. Therefore, we will evaluate Vorinostat when administered in combination with the regimen of Carboplatin, Paclitaxel and Bevacizumab for patients with previously untreated advanced non-small cell lung cancer.

Eligibility

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

Criteria

Inclusion Criteria:

Advanced non-squamous NSCLC
No prior chemotherapy for advanced disease
ECOG performance status 0 or 1
Measurable disease
Life expectancy > 3 months
Normal bone marrow, renal and hepatic function
Ability to take oral medications
Willingness to sign informed consent

Exclusion Criteria:

History of brain metastasis
Evidence of thromboembolic phenomenon and treatment with anticoagulants
Pregnancy
Uncontrolled inter-current illness
Prior therapy with Paclitaxel

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00702572

Contacts

Contact: Chandra P. Belani, MD	717-531-1078	cbelani@hmc.psu.edu
Contact: Rebecca Miller, RN	717-531-1003	rmiller13@hmc.psu.edu

Locations

United States, Pennsylvania
Penn State College of Medicine, Penn State Milton S. Hershey Medical Center	Recruiting
Hershey, Pennsylvania, United States, 17033
Contact: Chandra P Belani, MD 717-531-1078 cbelani@hmc.psu.edu

Sponsors and Collaborators

Penn State University

Investigators

Principal Investigator:

Chandra P Belani, MD

Penn State College of Medicine

More Information

No publications provided

Responsible Party:	Chandra P. Belani, MD, Penn State Cancer Institute
ClinicalTrials.gov Identifier:	NCT00702572 History of Changes
Other Study ID Numbers:	PSHCI 08-004
Study First Received:	June 19, 2008
Last Updated:	July 19, 2011
Health Authority:	United States: Institutional Review Board

Keywords provided by Penn State University:

Phase I
Advanced non-small cell lung cancer

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Vorinostat
Bevacizumab
Carboplatin
Paclitaxel
Antineoplastic Agents

Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic
Histone Deacetylase Inhibitors
Enzyme Inhibitors
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors

ClinicalTrials.gov processed this record on February 09, 2012