Clinical trial NCT01137968: Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy in Non-small Cell Lung Cancer (NSCLC)
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 type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Geron Corporation
Sponsor class: INDUSTRY
First posted: 2010-06-07
Enrollment: 116
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Progression-free survival
timeFrame: 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:
measure: Objective response
timeFrame: Occurring post randomization through end of study period (8 mos. after the last participant is randomized)
measure: Time to all-cause mortality
timeFrame: From the date of randomization through end of study period (8 mos. after the last participant is randomized)
measure: Safety and tolerability
timeFrame: From the date of randomization through the end of the study period (8 mos. after the last participant is randomized)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: Achieve Clinical Research, Llc
state: Alabama
city: Huntsville
country: United States
facility: Clearview Cancer Institute
state: Alabama
city: Anaheim
country: United States
facility: Pacific Cancer Medical Center, Inc.
state: California
city: Fresno
country: United States
facility: Cancer Care Associates of Fresno Medical Group Inc
state: California
city: Orange
country: United States
facility: St. Joseph's Hospital
state: California
city: Vallejo
country: United States
facility: Kaiser Permanente Medical Center
state: California
city: Aurora
country: United States
facility: University of Colorado Denver School of Medicine
state: Colorado
city: Fort Myers
country: United States
facility: Florida Cancer Specialists
state: Florida
city: Jacksonville
country: United States
facility: Integrated Community Oncology Network
state: Florida
city: Tampa
country: United States
facility: H. Moffitt Lee Cancer Center
state: Florida
city: Harvey
country: United States
facility: Ingalls Memorial Hospital
state: Illinois
city: Wichita
country: United States
facility: Cancer Center of Kansas
state: Kansas
city: Mt. Sterling
country: United States
facility: Montgomery Cancer Center
state: Kentucky
city: Baltimore
country: United States
facility: Auerbach Hematology Oncology
state: Maryland
city: Detroit
country: United States
facility: Karmanos Cancer Institute
state: Michigan
city: Billings
country: United States
facility: Hematology Oncology Centers
state: Montana
city: Charlotte
country: United States
facility: Blumenthal Cancer Center
state: North Carolina
city: Portland
country: United States
facility: Kaiser Northwest
state: Oregon
city: Columbia
country: United States
facility: South Carolina Oncology Associates
state: South Carolina
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
city: Nashville
country: United States
facility: Sarah Cannon Research Institute
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center
state: Texas
city: Temple
country: United States
facility: Scott and White Memorial Hospital (Texas A & M)
state: Texas
city: Seattle
country: United States
facility: Swedish Cancer Institute
state: Washington
city: Tacoma
country: United States
facility: Northwest Medical Specialties
state: Washington
city: Madison
country: United States
facility: University of Wisconsin
state: Wisconsin
city: Greenfield Park
country: Canada
facility: Hôpital Charles Lemoyne
state: Quebec
city: Montreal
country: Canada
facility: Hospital Notre-Dame
state: Quebec
city: Grosshansdorf
country: Germany
facility: Krankenhaus Grosshansdorf
state: Hamburg
city: Gauting
country: Germany
facility: Asklepios Klinik Gauting GmbH
state: Munich
city: Munchen
country: Germany
facility: Klinikum rechts der Isar der TU München
state: Munich
city: Frankfurt
country: Germany
facility: Krankenhaus Nordwest
city: Mainz
country: Germany
facility: Universitaetsklinikum Mainz
Study officials:
affiliation: University of Texas
name: Joan Schiller, MD
role: PRINCIPAL_INVESTIGATOR
References: