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

Titan Pharmaceuticals

Status and phase

Completed

Phase 2

Conditions

Carcinoma, Non-Small-Cell Lung

Treatments

Drug: Pivanex

Drug: Docetaxel

Study type

Interventional

Funder types

Industry

Identifiers

NCT00073385

TTP-200-03-01

NSCLC Clincal Trial

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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).