Study of GRN163L With Paclitaxel and Carboplatin in Patients With Advanced or Metastatic Non Small Cell Lung Cancer

A Phase I Study of GRN163L in Combination With Paclitaxel and Carboplatin in Patients With Advanced or Metastatic Non-Small Cell Lung Cancer

The purpose of this study is to determine the safety and the maximum tolerated dose (MTD) of GRN163L when administered in combination with a standard paclitaxel/carboplatin regimen to patients with advanced or metastatic non-small cell lung cancer.

Study Overview

• Status: Completed
• Conditions: Lung Cancer
• Intervention / Treatment: Drug: Imetelstat Sodium (GRN163L)

Detailed Description

GRN163L is a telomerase template antagonist with in vitro and in vivo activity in a variety of tumor model systems. Telomerase is an enzyme that is active primarily in tumor cells and is crucial for the indefinite growth of tumor cells. Inhibition of telomerase may result in antineoplastic effects.

• Study Type: Interventional
• Enrollment (Actual): 27
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21201
      • University of Maryland Greenebaum Cancer Center
  • Texas
    • Dallas, Texas, United States, 75390
      • The University of Texas Southwestern Medical Center
    • Houston, Texas, United States, 77030
      • UT MD Anderson Cancer Center
  • Wisconsin
    • Madison, Wisconsin, United States, 53792
      • University of Wisconsin, Paul P. Carbone Comprehensive Cancer Center

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 diagnosis of NSCLC
• Stage IIIb with pleural effusion, Stage IV, or recurrent disease
• Measurable or evaluable disease by RECIST criteria
• ECOG performance status 0-1
• Adequate hepatic/renal function and platelet count
• If previously treated with an anthracycline, anthracenedione, or trastuzumab, must have left ventricular ejection fraction > 50%

Exclusion Criteria:

• More than 2 prior chemotherapy regimens for metastatic disease (prior adjuvant chemotherapy is allowed)
• Tumor progression during treatment with paclitaxel (refractory to paclitaxel)
• Taxane-based regimen within 12 weeks
• Any systemic therapy for cancer within 4 weeks
• Anti-platelet therapy within 2 weeks, other than low dose aspirin prophylaxis therapy
• Therapeutic anticoagulation therapy except for low dose warfarin (eg, 1 mg by mouth per day)
• Radiation therapy within 3 weeks
• Major surgery within 4 weeks (central line placement is allowed)
• Prolongation of PT or aPTT > the ULN or fibrinogen < the LLN
• History of or active central nervous system metastatic disease
• Any other active malignancy
• Active or chronically recurrent bleeding (eg, active peptic ulcer disease)
• Clinically significant infection
• Active autoimmune disease requiring immunosuppressive therapy
• Clinically significant cardiovascular disease or condition

Study Plan

How is the study designed?

Design Details

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

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Single Arm Trial; Patients will be enrolled in the order of confirmation of eligibility. Dose cohorts will be filled sequentially with a minimum of 3 patients. Once assigned to a dose cohort, each patient will continue to be treated at the same dose level throughout the course of the study.	Drug: Imetelstat Sodium (GRN163L); The starting dose of GRN163L for this study will be 3.2 mg/kg. Subsequent dose levels will be 4.8, 6, 7.5, 9, 11, and 13.5 mg/kg. The maximum dose to be administered will not exceed 13.5 mg/kg. Paclitaxel and carboplatin will be administered on Day 2 of each 21-day cycle.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Safety and MTD	First 3 weeks

Secondary Outcome Measures

Outcome Measure	Time Frame
PK and efficacy	Baseline to end of treatment

Collaborators and Investigators

• Sponsor: Geron Corporation

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start: July 1, 2007
• Primary Completion (Actual): April 1, 2011
• Study Completion (Actual): April 1, 2011

Study Registration Dates

• First Submitted: July 31, 2007
• First Submitted That Met QC Criteria: July 31, 2007
• First Posted (Estimate): August 2, 2007

Study Record Updates

• Last Update Posted (Estimate): December 24, 2015
• Last Update Submitted That Met QC Criteria: December 22, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Keywords: Non Small Cell Lung Cancer; Metastatic Non Small Cell Lung Cancer; Advanced Non Small Cell Lung Cancer
• 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; Protein Kinase Inhibitors; Imetelstat; Motesanib diphosphate
• Other Study ID Numbers: GRN163L CP14A005