Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy in Non-small Cell Lung Cancer (NSCLC)

NCT01137968 | Completed Phase 2

• 1 other identifier: CP14B012
• Study Type: interventional
• Target: 116
• Locations: 3 countries
• Sites: 33

Brief Summary

The purpose of this is to evaluate the efficacy and safety of imetelstat (GRN163L) as maintenance therapy for patients with advanced stage NSCLC who have not progressed after 4 cycles of platinum based therapy. Participants will be randomized in a 2:1 ratio to imetelstat + standard of care versus standard of care alone. Participants who received bevacizumab with their induction chemotherapy will continue to receive bevacizumab on this study.

Conditions

Non-small Cell Lung Cancer

Keywords

imetelstat; imetelstat sodium; GRN163L; telomerase inhibitor; telomerase inhibition; maintenance therapy; non-small cell lung cancer; relapsed non-small cell lung cancer; advanced non-small cell lung cancer; NSCLC, cancer stem cells; Bevacizumab; post induction chemotherapy

Outcome Measures

Primary Outcomes (1)

• Progression-free survival

  Defined as the time from randomization to documented disease progression or death, whichever occurs earlier,as determined by the Investigator's assessment according to RECIST, or death from any cause, whichever occurs earlier.

  From randomization to documented disease progression or death, whichever occurs earlier, through the end of the study period (8 mos. after the last participant is randomized)

Secondary Outcomes (3)

• Objective response

  Occurring post randomization through end of study period (8 mos. after the last participant is randomized)

• Time to all-cause mortality

  From the date of randomization through end of study period (8 mos. after the last participant is randomized)

• Safety and tolerability

  From the date of randomization through the end of the study period (8 mos. after the last participant is randomized)

Study Arms (2)

imetelstat plus standard of care

EXPERIMENTAL

imetelstat plus standard of care (bevacizumab or observation)

Drug: imetelstat; Drug: Bevacizumab

Standard of care

OTHER

Bevacizumab or observation

Drug: Bevacizumab

Interventions

imetelstat DRUG

9.4 mg/kg over a 2 hour IV infusion on Day 1 and Day 8 of each 21 day cycle until disease progression.

Also known as: GRN163L

imetelstat plus standard of care

Bevacizumab DRUG

Dosage and duration will be according to the FDA-approved bevacizumab package insert. Bevacizumab will be administered on Day 1 of each 21-day cycle.

Also known as: Avastin

Standard of care; imetelstat plus standard of care

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signed informed consent.
• Ability and willingness to comply with requirements of the study protocol.
• Male or female, age 18 or over.
• Histologically or cytologically confirmed diagnosis of NSCLC
• Stage IV (using the 7th edition of AJCC, or wet IIIb / IV using the 6th edition), or recurrent locally advanced disease not amenable to radiation or surgery with curative intent and not amenable to concurrent chemoradiation.
• Patients have completed four to six cycles of platinum-based chemotherapy doublet for first line, advanced NSCLC, with no evidence of disease progression according to RECIST version 1.1. Adjuvant chemotherapy greater than one year prior to progression is allowed.
• Patients are willing and able to continue treatment with bevacizumab, if they received it with their platinum based chemotherapy.
• ECOG performance status 0-1
• Adequate bone marrow reserve as measured by ANC ≥ 1500/mm3, hemoglobin
• ≥ 9 g/dL, platelet count ≥ 75,000 μL. Must be measured ≥ 1 week after last transfusion of blood products and/or last dose of hematopoietic growth factor.
• Prothrombin time (PT) or INR or aPTT ≤ 1.5 x ULN.
• Serum creatinine \< 1.5 mg/dL or creatinine clearance \> 45 mL/min.
• Urinalysis with \< 2+ protein or urinary excretion of \< 2 g of protein/day (for patients to receive bevacizumab).
• AST (SGOT) and ALT (SGPT) \< 2.5 x the ULN, (AST (SGOT) and ALT (SGPT) \< 5 x the ULN if documented liver metastases).
• Serum bilirubin \< 2.0 mg/dL (patients with Gilbert's syndrome: serum bilirubin \< 3 x ULN).

You may not qualify if:

• Patients who meet any of the following criteria will be excluded from screening and study entry:
• Patients who are not eligible for induction therapy with a platinum based chemotherapy doublet.
• Patients who have received, or are scheduled to receive pemetrexed or erlotinib as maintenance therapy.
• Patients receiving bevacizumab must not have a recent history of hemoptysis ≥ ½ teaspoon of red blood or history of ≥ 2 g/24 hr urine protein while receiving prior bevacizumab, or squamous cell histology.
• Patients will be excluded from being randomized if any of the following criteria apply:
• Last dose of induction chemotherapy \< 21 days prior to randomization or \> 42 days prior to randomization
• History of pulmonary hemorrhage (\> 1 teaspoon) within the 4 weeks prior to randomization.
• Anti-platelet therapy within 2 weeks prior to randomization, other than low dose aspirin prophylaxis therapy.
• Therapeutic anticoagulation therapy except for low dose warfarin (e.g., 1 mg by mouth per day).
• Radiation therapy within 3 weeks prior to randomization (palliative radiation therapy is allowed, provided that sites of bone marrow production, i.e. iliac crests are not in the radiation field)
• Major surgery within 4 weeks prior to first study drug administration (central line placement is allowed)
• Active central nervous system (CNS) metastatic disease. Patients with stable CNS disease following completion of radiation therapy and/or surgery are eligible.
• Any other active malignancy
• Active or chronically recurrent bleeding (e.g., active peptic ulcer disease)
• Clinically significant infection

Sponsors & Collaborators

• Geron Corporation: lead

Study Sites (33)

Achieve Clinical Research, Llc

Birmingham, Alabama, 35216, United States

Location

Clearview Cancer Institute

Huntsville, Alabama, 35805, United States

Location

Pacific Cancer Medical Center, Inc.

Anaheim, California, 92801, United States

Location

Cancer Care Associates of Fresno Medical Group Inc

Fresno, California, 93720, United States

Location

St. Joseph's Hospital

Orange, California, 92868, United States

Location

Kaiser Permanente Medical Center

Vallejo, California, 94589, United States

Location

University of Colorado Denver School of Medicine

Aurora, Colorado, 80045, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33901, United States

Location

Integrated Community Oncology Network

Jacksonville, Florida, 32256, United States

Location

H. Moffitt Lee Cancer Center

Tampa, Florida, 33612, United States

Location

Ingalls Memorial Hospital

Harvey, Illinois, 60426, United States

Location

Cancer Center of Kansas

Wichita, Kansas, 67214, United States

Location

Montgomery Cancer Center

Mount Sterling, Kentucky, 40353, United States

Location

Auerbach Hematology Oncology

Baltimore, Maryland, 21237, United States

Location

Karmanos Cancer Institute

Detroit, Michigan, 48201, United States

Location

Hematology Oncology Centers

Billings, Montana, 59101, United States

Location

Blumenthal Cancer Center

Charlotte, North Carolina, 28204, United States

Location

Kaiser Northwest

Portland, Oregon, 97227, United States

Location

South Carolina Oncology Associates

Columbia, South Carolina, 29210, United States

Location

The Jones Clinic

Germantown, Tennessee, 38138, United States

Location

Sarah Cannon Research Institute

Nashville, Tennessee, 37203, United States

Location

UT Southwestern Medical Center

Dallas, Texas, 75390, United States

Location

Scott and White Memorial Hospital (Texas A & M)

Temple, Texas, 76508, United States

Location

Swedish Cancer Institute

Seattle, Washington, 98104, United States

Location

Northwest Medical Specialties

Tacoma, Washington, 98405, United States

Location

University of Wisconsin

Madison, Wisconsin, 53792, United States

Location

Hôpital Charles Lemoyne

Greenfield Park, Quebec, J4V 2H1, Canada

Location

Hospital Notre-Dame

Montreal, Quebec, H2L 4M1, Canada

Location

Krankenhaus Nordwest

Frankfurt, Frankfurt, 60488, Germany

Location

Krankenhaus Grosshansdorf

Grosshansdorf, Hamburg, 22927, Germany

Location

Universitaetsklinikum Mainz

Mainz, Mainz, 55131, Germany

Location

Asklepios Klinik Gauting GmbH

Gauting, Munich, 82131, Germany

Location

Klinikum rechts der Isar der TU München

München, Munich, Germany

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

imetelstat; GRN163L peptide; Bevacizumab

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins

Study Officials

• Joan Schiller, MD

  University of Texas

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 3, 2010
• First Posted: June 7, 2010
• Study Start: May 1, 2010
• Primary Completion: September 1, 2013
• Study Completion: September 1, 2013
• Last Updated: January 26, 2016

Record last verified: 2015-03

Locations

DE (5); US (26); CA (2)