Safety and Dose Study of GRN163L Administered to Patients With Refractory or Relapsed Solid Tumor Malignancies

Study Overview
=================
Brief Summary
-----------------
The purpose of this study is to determine the safety and the maximum tolerated dose of GRN163L administration in treating patients with refractory or relapsed solid tumor malignancies.

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.

Official Title
-----------------
A Phase I, Sequential Cohort, Dose Escalation Trial to Determine the Safety, Tolerability, and MTD of GRN163L in Patients With Refractory or Relapsed Solid Tumor Malignancies

Conditions
-----------------
Solid Tumor Malignancies

Intervention / Treatment
-----------------
* Drug: Imetelstat Sodium (GRN163L)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: 18 years of age or older Male or female Measurable or evaluable solid tumor malignancy Relapsed, refractory, locally advanced, or metastatic disease Disease refractory to or not amenable to standard therapy Karnofsky performance status 70-100% Life expectancy 3 months or greater Exclusion Criteria: Pregnant or lactating women Primary central nervous system(CNS) malignancy or active CNS metastases Hematologic malignancy Chemotherapy within 4 weeks prior to study Mitomycin C, nitrosoureas within 6 weeks prior to study High dose chemotherapy with stem cell support within 6 months prior to study Signal transduction inhibitors, monoclonal antibodies, etc. within 4 weeks prior to study Systemic hormonal therapy within 4 weeks prior to study Anticoagulant therapy, antiplatelet therapy within 2 weeks prior to study Radiotherapy within 4 weeks prior to study Significant cardiovascular disease Serious/active infection Major surgical procedures within 2 weeks

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Dose escalation<br>Treatment Schedule 3 will consist of dosing on Days 1, 4, 8, and 11 of each 21 day cycle (3 weeks equals 1 cycle) and Treatment Schedule 4 will consist of dosing on Day 1 of each 28 day cycle (4 weeks equals 1 cycle) | Drug: Imetelstat Sodium (GRN163L)<br>* Dose increase by 25% if tolerated infused over 2 hours<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety, DLT, and MTD |  | Measured during the first cycle of treatment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PK profile and disease response |  | Within the first 2 cycles of treatment | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Refractory, Relapsed