Maximum Tolerated Dose, Safety and Efficacy of Docetaxel / Cisplatin + STI571

A Phase I - II Open Label Study of the Maximum Tolerated Dose, Safety and Efficacy of Docetaxel and Cisplatin Plus STI571 in Advanced Non-Small Cell Lung Cancer

This is a Phase 1/Phase 2 study of STI571 combined with docetaxel and cisplatin for treatment of patients with recurrent and metastatic Non-Small Cell Lung Cancer (NSCLC).

This research study has 2 parts to it. The first part (Phase 1) is called a dose-escalation. Not all subjects enrolled into this phase of the study will receive the same dose. The purpose of the dose-escalation is to determine the highest safe dose of STI571 that can be used in combination with docetaxel and cisplatin. That dose will be used in Phase 2.

Study Overview

• Status: Terminated
• Conditions: Non-small Cell Lung Cancer
• Intervention / Treatment: Drug: Docetaxel; Drug: Cisplatin; Drug: Docetaxel, Cisplatin and STI571

• Study Type: Interventional
• Enrollment (Actual): 43
• Phase: Phase 2; Phase 1

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:

• Patients must have histologically or cytologically recurrent, or advanced NSCLC: Stage IV disease; or Stage IIIB due to malignant pleural effusion is allowed- only if successfully pleurodesed.
• Tumor tissue slides must express phosophorylated pdgf-rB by IHC.
• At least one measurable target lesion as defined by RECIST criteria that has not been irradiated.
• No prior chemotherapy treatment for this disease will be allowed. Patients with brain metastasis will have to be, after appropriate treatment, neurologically stable for at least 1-2 weeks (off steroids) prior to study enrollment.
• ECOG performance status 0-1.
• Meets initial laboratory parameters.
• Men and women of childbearing potential must be willing to consent to using effective contraception while on treatment and for at least 3 months thereafter.

Exclusion Criteria

• Any prior treatment with a biologic response modifier or chemotherapeutic agent for this disease.
• Any concomitant malignancy except non-melanoma skin cancer or in-situ carcinoma of the cervix.
• History of allergic reactions attributed to compounds of similar chemical or biologic composition to STI571 and/or docetaxel, or other drugs formulated with polysorbate 80 and/or cisplatin.

• Patients with:

  • Contrast allergy.
  • GI bleed ≤ 1 month from study enrollment.
  • Intermittent or chronic oxygen requirements.
  • Pulse oximetry <90%.
  • Grade 3 dyspnea.
  • History of poorly regulated anticoagulation with warfarin.
  • Edema or fluid retention grade >1.
  • Neuropathy grade ≥1.
• Uncontrolled inter-current medical illness including, but not limited to, ongoing or active infection requiring IV antibiotics, symptomatic congestive heart failure, unstable angina pectoris, ≤3 months myocardial infarction or cardiac arrhythmia.
• Psychiatric illness/social situations that would limit compliance with study requirement or that would prevent informed consent or psychiatric illness/social situations requiring inpatient treatment within the past 3 months.
• Any type of hearing impairment.
• Known HIV infection.
• Receiving other investigational agents.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 1 - Maximum Tolerated Dose (MTD) of STI571	To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin, when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC.	After cycle 1, day 22
Phase 1 - Maximum Tolerated Dose (MTD) of Docetaxel and Cisplatin	To determine the maximum tolerated dose (MTD) of STI571, docetaxel, and cisplatin when administered in combination for the treatment of patients with chemo-naïve recurrent and metastatic (stage IV) NSCLC.	After cycle 1, day 22
Phase II - Radiographic Response	The percentage of patients with a complete or partial response. Responses for the Phase II portion of the trial will be by Response Evaluation Criteria In Solid Tumors (RECIST) criteria as follows: Complete Response (CR): disappearance of all target lesions; Partial Response (PR): at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD.	After Cycle 6, approximately 18 weeks.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Phase 2: 1 Year Survival	Phase II: Percentage of patients alive 1 year from the start of protocol treatment.	1 year
Change in Gd-MRI Measurement	The change in Gd-MRI perfusion/permeability measurement between pre and post 7-day of STI571 treatment.	Day 7

Collaborators and Investigators

• Sponsor: Duke University
• Investigators: Principal Investigator: Gordana Vlahovic, MD, MHS, Duke University

Study record dates

Study Major Dates

• Study Start: November 1, 2004
• Primary Completion (Actual): June 1, 2010
• Study Completion (Actual): December 1, 2010

Study Registration Dates

• First Submitted: April 24, 2014
• First Submitted That Met QC Criteria: April 28, 2014
• First Posted (Estimate): April 30, 2014

Study Record Updates

• Last Update Posted (Estimate): September 15, 2014
• Last Update Submitted That Met QC Criteria: September 12, 2014
• Last Verified: September 1, 2014

More Information

Terms related to this study

• Keywords: lung cancer; non-small cell
• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Neoplasms; Lung Diseases; Neoplasms by Site; Respiratory Tract Neoplasms; Thoracic Neoplasms; Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Carcinoma, Non-Small-Cell Lung; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Protein Kinase Inhibitors; Docetaxel; Cisplatin; Imatinib Mesylate
• Other Study ID Numbers: Pro00008205