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

Phase 2

Completed

• Conditions: Non-small Cell Lung Cancer
• Interventions: Drug: Bevacizumab; Drug: imetelstat

• Registration Number: NCT01137968
• Lead Sponsor: Geron Corporation

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2010-05
• Study First Submitted: 2010-06-03
• Study First Submitted QC: 2010-06-04
• Study First Posted: 2010-06-07
• Primary Completion: 2013-09
• Study Completion: 2013-09
• Status Verified: 2015-03
• Disposition First Submitted: 2015-03-13
• Disposition First Submitted QC: 2015-03-13
• Disposition First Posted: 2015-04-02
• Last Update Submitted: 2015-12-22
• Last Update Posted: 2016-01-26

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 116

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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Standard of care	Bevacizumab	Bevacizumab or observation
imetelstat plus standard of care	imetelstat	imetelstat plus standard of care (bevacizumab or observation)
imetelstat plus standard of care	Bevacizumab	imetelstat plus standard of care (bevacizumab or observation)

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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.
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.
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.

Trial Locations

Locations (33)

Integrated Community Oncology Network; 🇺🇸 Jacksonville, Florida, United States

Cancer Center of Kansas; 🇺🇸 Wichita, Kansas, United States

Ingalls Memorial Hospital; 🇺🇸 Harvey, Illinois, United States

Hematology Oncology Centers; 🇺🇸 Billings, Montana, United States

University of Wisconsin; 🇺🇸 Madison, Wisconsin, United States

Hospital Notre-Dame; 🇨🇦 Montreal, Quebec, Canada

Hôpital Charles Lemoyne; 🇨🇦 Greenfield Park, Quebec, Canada

Klinikum rechts der Isar der TU München; 🇩🇪 Munchen, Munich, Germany

Krankenhaus Grosshansdorf; 🇩🇪 Grosshansdorf, Hamburg, Germany

Asklepios Klinik Gauting GmbH; 🇩🇪 Gauting, Munich, Germany

Krankenhaus Nordwest; 🇩🇪 Frankfurt, Germany

Universitaetsklinikum Mainz; 🇩🇪 Mainz, Germany

Achieve Clinical Research, Llc; 🇺🇸 Birmingham, Alabama, United States

Clearview Cancer Institute; 🇺🇸 Huntsville, Alabama, United States

St. Joseph's Hospital; 🇺🇸 Orange, California, United States

Montgomery Cancer Center; 🇺🇸 Mt. Sterling, Kentucky, United States

Blumenthal Cancer Center; 🇺🇸 Charlotte, North Carolina, United States

Northwest Medical Specialties; 🇺🇸 Tacoma, Washington, United States

Scott and White Memorial Hospital (Texas A & M); 🇺🇸 Temple, Texas, United States

Pacific Cancer Medical Center, Inc.; 🇺🇸 Anaheim, California, United States

Cancer Care Associates of Fresno Medical Group Inc; 🇺🇸 Fresno, California, United States

Kaiser Permanente Medical Center; 🇺🇸 Vallejo, California, United States

Auerbach Hematology Oncology; 🇺🇸 Baltimore, Maryland, United States

South Carolina Oncology Associates; 🇺🇸 Columbia, South Carolina, United States

Sarah Cannon Research Institute; 🇺🇸 Nashville, Tennessee, United States

UT Southwestern Medical Center; 🇺🇸 Dallas, Texas, United States

Swedish Cancer Institute; 🇺🇸 Seattle, Washington, United States

Karmanos Cancer Institute; 🇺🇸 Detroit, Michigan, United States

H. Moffitt Lee Cancer Center; 🇺🇸 Tampa, Florida, United States

University of Colorado Denver School of Medicine; 🇺🇸 Aurora, Colorado, United States

Kaiser Northwest; 🇺🇸 Portland, Oregon, United States

Florida Cancer Specialists; 🇺🇸 Fort Myers, Florida, United States

The Jones Clinic; 🇺🇸 Germantown, Tennessee, United States