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

Sponsor
Geron Corporation (Industry)
Overall Status
Completed
CT.gov ID
NCT01137968
Collaborator
(none)
116
33
2
40
3.5
0.1

Study Details

Study Description

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.

Condition or Disease Intervention/Treatment Phase
Phase 2

Study Design

Study Type:
Interventional
Actual Enrollment :
116 participants
Allocation:
Randomized
Intervention Model:
Parallel Assignment
Masking:
None (Open Label)
Primary Purpose:
Treatment
Official Title:
A Randomized Phase II Study of Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy for Advance Non-small Cell Lung Cancer(NSCLC)
Study Start Date :
May 1, 2010
Actual Primary Completion Date :
Sep 1, 2013
Actual Study Completion Date :
Sep 1, 2013

Arms and Interventions

Arm Intervention/Treatment
Experimental: imetelstat plus standard of care

imetelstat plus standard of care (bevacizumab or observation)

Drug: imetelstat
9.4 mg/kg over a 2 hour IV infusion on Day 1 and Day 8 of each 21 day cycle until disease progression.
Other Names:
  • GRN163L
  • Drug: Bevacizumab
    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.
    Other Names:
  • Avastin
  • Other: Standard of care

    Bevacizumab or observation

    Drug: Bevacizumab
    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.
    Other Names:
  • Avastin
  • Outcome Measures

    Primary Outcome Measures

    1. Progression-free survival [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)]

      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.

    Secondary Outcome Measures

    1. Objective response [Occurring post randomization through end of study period (8 mos. after the last participant is randomized)]

      Objective response (partial response plus complete response) occurring post-randomization as determined by the Investigator's assessment according to RECIST criteria using post-induction tumor dimensions as a baseline.

    2. Time to all-cause mortality [From the date of randomization through end of study period (8 mos. after the last participant is randomized)]

      Defined as the time from the date of radomization to death from any cause during the study period.

    3. Safety and tolerability [From the date of randomization through the end of the study period (8 mos. after the last participant is randomized)]

      Safety and tolerability will be assessed by the incidence, nature, and severity of adverse events, laboratory abnormalities, and vital signs.

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    18 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    Inclusion Criteria:
    • 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).

    • Alkaline phosphatase < 2.5 x ULN (patients with documented liver or bone metastases, alkaline phosphatase ≤ 5 x ULN).

    • No other obvious related major organ toxicities which would compromise the patient's ability to participate in a clinical trial of a novel agent.

    • Patients may have received prior radiation therapy for local or locally advanced disease providing that any clinically significant adverse effects associated with prior therapy have recovered to Grade 1 or less.

    • Women of childbearing potential must have a negative serum pregnancy test and agree to use effective birth control during and for 12 weeks after the last treatment with imetelstat.

    • Males must agree to use effective birth control for themselves or their partner during and for 12 weeks after the last treatment with imetelstat.

    Exclusion Criteria:

    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

    • Active autoimmune disease requiring immunosuppressive therapy

    • Clinically significant cardiovascular disease or condition including:

    • Congestive heart failure (CHF) requiring therapy

    • Need for anti-arrhythmic therapy for a ventricular arrhythmia

    • Severe conduction disturbance

    • Angina pectoris requiring therapy

    • Medically uncontrolled hypertension per the Investigator's discretion

    • Myocardial infarction within 6 months prior to first study drug administration

    • New York Heart Association Class II, III, or IV cardiovascular disease

    • Any other severe, acute, or chronic medical or psychiatric condition, laboratory abnormality, or difficulty complying with protocol requirements that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results and, in the judgment of the Investigator, would make the patient inappropriate for the study.

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Achieve Clinical Research, Llc Birmingham Alabama United States 35216
    2 Clearview Cancer Institute Huntsville Alabama United States 35805
    3 Pacific Cancer Medical Center, Inc. Anaheim California United States 92801
    4 Cancer Care Associates of Fresno Medical Group Inc Fresno California United States 93720
    5 St. Joseph's Hospital Orange California United States 92868
    6 Kaiser Permanente Medical Center Vallejo California United States 94589
    7 University of Colorado Denver School of Medicine Aurora Colorado United States 80045
    8 Florida Cancer Specialists Fort Myers Florida United States 33901
    9 Integrated Community Oncology Network Jacksonville Florida United States 32256
    10 H. Moffitt Lee Cancer Center Tampa Florida United States 33612
    11 Ingalls Memorial Hospital Harvey Illinois United States 60426
    12 Cancer Center of Kansas Wichita Kansas United States 67214
    13 Montgomery Cancer Center Mt. Sterling Kentucky United States 40353
    14 Auerbach Hematology Oncology Baltimore Maryland United States 21237
    15 Karmanos Cancer Institute Detroit Michigan United States 48201
    16 Hematology Oncology Centers Billings Montana United States 59101
    17 Blumenthal Cancer Center Charlotte North Carolina United States 28204
    18 Kaiser Northwest Portland Oregon United States 97227
    19 South Carolina Oncology Associates Columbia South Carolina United States 29210
    20 The Jones Clinic Germantown Tennessee United States 38138
    21 Sarah Cannon Research Institute Nashville Tennessee United States 37203
    22 UT Southwestern Medical Center Dallas Texas United States 75390
    23 Scott and White Memorial Hospital (Texas A & M) Temple Texas United States 76508
    24 Swedish Cancer Institute Seattle Washington United States 98104
    25 Northwest Medical Specialties Tacoma Washington United States 98405
    26 University of Wisconsin Madison Wisconsin United States 53792
    27 Hôpital Charles Lemoyne Greenfield Park Quebec Canada J4V 2H1
    28 Hospital Notre-Dame Montreal Quebec Canada H2L 4M1
    29 Krankenhaus Grosshansdorf Grosshansdorf Hamburg Germany 22927
    30 Asklepios Klinik Gauting GmbH Gauting Munich Germany 82131
    31 Klinikum rechts der Isar der TU München Munchen Munich Germany
    32 Krankenhaus Nordwest Frankfurt Germany 60488
    33 Universitaetsklinikum Mainz Mainz Germany 55131

    Sponsors and Collaborators

    • Geron Corporation

    Investigators

    • Principal Investigator: Joan Schiller, MD, University of Texas

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    None provided.
    Responsible Party:
    Geron Corporation
    ClinicalTrials.gov Identifier:
    NCT01137968
    Other Study ID Numbers:
    • CP14B012
    First Posted:
    Jun 7, 2010
    Last Update Posted:
    Jan 26, 2016
    Last Verified:
    Mar 1, 2015

    Study Results

    No Results Posted as of Jan 26, 2016