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

September 21, 2016 updated by: Chandra P. Belani, Milton S. Hershey Medical Center

Phase I Study of Carboplatin, Paclitaxel, Bevacizumab and Vorinostat for Patients With Advanced Non-Small Cell Lung Cancer (NSCLC)

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

25

Phase

  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State College of Medicine, Penn State Milton S. Hershey Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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 Names:
  • SAHA
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 Names:
  • SAHA
Experimental: 2
Phase 2 will evaluate the toxicities and safety profile of the 4-drug regimen.
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 Names:
  • SAHA
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 Names:
  • SAHA

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Participants will be followed for survival, an expected average of two years.
An average of 2 years

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Participants will be followed for survival, an expected average of 2 years.
Average of 2 years

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Milton S. Hershey Medical Center

Investigators

  • Principal Investigator: Chandra P Belani, MD, Penn State College of Medicine

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

April 1, 2008

Primary Completion (Actual)

May 1, 2016

Study Completion (Actual)

September 1, 2016

Study Registration Dates

First Submitted

June 19, 2008

First Submitted That Met QC Criteria

June 19, 2008

First Posted (Estimate)

June 20, 2008

Study Record Updates

Last Update Posted (Estimate)

September 22, 2016

Last Update Submitted That Met QC Criteria

September 21, 2016

Last Verified

September 1, 2016

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • PSHCI 08-004

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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