Comparative Trial of Pivanex and Docetaxel Vs Docetaxel Monotherapy in Patients With Advanced Non-Small Cell Lung Cancer

A Randomized Trial of Pivanex Plus Docetaxel or Docetaxel Monotherapy in Patients With Chemotherapy Resistant Advanced Non-Small Cell Carcinoma of the Lung (NSCLC)

This randomized study will assess the efficacy and safety of the combination of Pivanex and docetaxel compared to docetaxel alone in patients with a type of lung cancer called non-small cell lung cancer. Pivanex is an investigational agent, and docetaxel is an approved drug.

Study Overview

• Status: Completed
• Conditions: Carcinoma, Non-Small-Cell Lung
• Intervention / Treatment: Drug: Docetaxel; Drug: Pivanex

Detailed Description

Rationale: Pivanex is a histone deacetylase inhibitor that induces tumor differentiation and/or apoptosis. Pivanex has been well tolerated in clinical trials and has shown preliminary evidence of efficacy in patients with non-small cell lung cancer. Docetaxel is an approved drug for second-line treatment of non-small cell lung cancer. Preclinical studies indicate that the combination of Pivanex and docetaxel is synergistic.

Purpose: This open-label randomized trial will evaluate whether combination therapy with Pivanex and docetaxel provides clinical benefit over docetaxel alone in patients with chemotherapy resistant non-small cell lung cancer.

Objectives:

• Compare the survival of patients with non-small cell lung cancer treated with combination therapy with Pivanex and docetaxel vs. docetaxel alone
• Compare the time to disease progression, tumor responses, and safety profile of patients with non-small cell lung cancer treated with combination therapy with Pivanex and docetaxel vs. docetaxel alone

Outline: This is a randomized, open-label, multicenter study in patients with non-small cell lung cancer who have previously been treated with no more than one prior platinum containing chemotherapy regimen. Patients are stratified by ECOG performance status (0-1 vs. 2), response to prior platinum based chemotherapy (progression vs. CR/PR/SD) and prior taxane therapy (yes vs. no). Patients are randomized to 1 of 2 treatment arms.

• Arm A: Patients receive the combination of Pivanex intravenously on Days 1-3 and docetaxel intravenously on Day 4. Treatment repeats every 21 days until disease progression or treatment withdrawal.
• Arm B: Patients receive docetaxel intravenously on Day 1. Treatment repeats every 21 days until disease progression or treatment withdrawal.

• Study Type: Interventional
• Enrollment: 225
• Phase: Phase 2

Contacts and Locations

Study Locations

• India
  • New Delhi, India, 110 085
    • Rajiv Gandhi Cancer Institute & Research Center
  • Thiruvananthapuram, India, 695 011
    • Regional Cancer Centre
• United Kingdom
  • Edinburgh, United Kingdom, EH4 2XU
    • University of Edinburgh, Edinburgh Cancer Centre
• United States
  • California
    • La Verne, California, United States, 91750
      • Wilshire Oncology Medical Group
  • Louisiana
    • New Orleans, Louisiana, United States, 70115
      • Hematology And Oncology Specialists, Llc
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center, Department of Oncology
    • Brooklyn, New York, United States, 11235
      • HemOnCare
  • North Carolina
    • Gastonia, North Carolina, United States, 28054
      • Gaston Hematology & Oncology Associates

Participation Criteria

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:

• Histologically or cytologically confirmed non-small cell lung cancer (NSCLC); Treatment with one prior platinum-based chemotherapy regimen (Eligible patients may include:

  1. Patients previously treated with adjuvant or neoadjuvant chemotherapy (must be completed within 6 months prior to randomization) or
  2. Patients who have received chemotherapy for advanced or metastatic lung cancer);
• Recurrent or progressive NSCLC (local, distant, or both) following initial chemotherapy);
• Measurable or non-measurable disease;
• Males and females, age => 18 years;
• Adequate renal function with creatinine => 1.5 mg/dl;
• Adequate liver function with alkaline phosphatase => 2.5 X upper limit of normal, SGOT, and SGPT => 1.5 X upper limit of normal; and total bilirubin => upper limit of normal;
• Adequate bone marrow function: platelets > 100,000/mm3, hemoglobin => 9 g/dL, and absolute neutrophil count (ANC) => 1,500 cells/mm3;
• Able to give informed consent;
• Discontinuation of previous surgery, radiation therapy or cancer chemotherapy at least four weeks prior to randomization (six weeks if a prior nitrosourea or mitomycin C), with recovery from treatment-associated toxicity;
• A predicted life expectancy of at least 12 weeks; and
• ECOG performance status of 0, 1, or 2.

Exclusion Criteria:

• Receipt of more than one chemotherapy regimen for NSCLC;
• A second malignancy within the last 5 years other than curatively treated carcinoma-in-situ or non-melanoma skin cancer;
• Pregnant or lactating females (Females of childbearing potential must have a negative pregnancy test and all male and female patients of reproductive potential must agree to use adequate birth control);
• Known HIV-positive patients;
• Acute medical problems, such as ischemic heart or lung disease or uncontrolled systemic infection;
• Patients with any underlying medical conditions or circumstance, which would contraindicate therapy with study treatment, affect compliance or impair evaluation of study endpoints;
• Patients receiving investigational agents within 30 days of the screening visit;
• Known allergy to reagents in the study;
• Prior docetaxel therapy;
• Symptomatic or untreated brain metastases (Patients with brain metastases are eligible if they are clinically and neurologically stable for > 4 weeks since therapy (radiation therapy, radiosurgery/gamma knife; surgical resection) as determined by the investigator and either off corticosteroids or on a stable dose of corticosteroids).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Collaborators and Investigators

• Sponsor: Titan Pharmaceuticals

Study record dates

Study Major Dates

• Study Start: September 1, 2003
• Study Completion: October 1, 2004

Study Registration Dates

• First Submitted: November 19, 2003
• First Submitted That Met QC Criteria: November 20, 2003
• First Posted (Estimate): November 21, 2003

Study Record Updates

• Last Update Posted (Estimate): August 30, 2005
• Last Update Submitted That Met QC Criteria: August 26, 2005
• Last Verified: August 1, 2005

More Information

Terms related to this study

• Keywords: Lung cancer, Docetaxel, Histone deacetylase inhibitor
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms by Histologic Type; Neoplasms; Lung Diseases; Neoplasms by Site; Neoplasms, Glandular and Epithelial; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Carcinoma; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: TTP-200-03-01; NSCLC Clincal Trial