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

Non-small Cell Lung Cancer Clinical Trial

Official title:

A Randomized Phase II Study of Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy for Advance Non-small Cell Lung Cancer(NSCLC)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01137968
• Other study ID #: CP14B012
• Status: Completed
• Phase: Phase 2
• First received: June 3, 2010
• Last updated: December 22, 2015
• Start date: May 2010
• Est. completion date: September 2013

Study information

• Verified date: March 2015
• Source: Geron Corporation
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 116
• Est. completion date: September 2013
• Est. primary completion date: September 2013
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-small Cell Lung Cancer

Intervention

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.
• 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.

Locations

Country	Name	City	State
Canada	Hôpital Charles Lemoyne	Greenfield Park	Quebec
Canada	Hospital Notre-Dame	Montreal	Quebec
Germany	Krankenhaus Nordwest	Frankfurt
Germany	Asklepios Klinik Gauting GmbH	Gauting	Munich
Germany	Krankenhaus Grosshansdorf	Grosshansdorf	Hamburg
Germany	Universitaetsklinikum Mainz	Mainz
Germany	Klinikum rechts der Isar der TU München	Munchen	Munich
United States	Pacific Cancer Medical Center, Inc.	Anaheim	California
United States	University of Colorado Denver School of Medicine	Aurora	Colorado
United States	Auerbach Hematology Oncology	Baltimore	Maryland
United States	Hematology Oncology Centers	Billings	Montana
United States	Achieve Clinical Research, Llc	Birmingham	Alabama
United States	Blumenthal Cancer Center	Charlotte	North Carolina
United States	South Carolina Oncology Associates	Columbia	South Carolina
United States	UT Southwestern Medical Center	Dallas	Texas
United States	Karmanos Cancer Institute	Detroit	Michigan
United States	Florida Cancer Specialists	Fort Myers	Florida
United States	Cancer Care Associates of Fresno Medical Group Inc	Fresno	California
United States	The Jones Clinic	Germantown	Tennessee
United States	Ingalls Memorial Hospital	Harvey	Illinois
United States	Clearview Cancer Institute	Huntsville	Alabama
United States	Integrated Community Oncology Network	Jacksonville	Florida
United States	University of Wisconsin	Madison	Wisconsin
United States	Montgomery Cancer Center	Mt. Sterling	Kentucky
United States	Sarah Cannon Research Institute	Nashville	Tennessee
United States	St. Joseph's Hospital	Orange	California
United States	Kaiser Northwest	Portland	Oregon
United States	Swedish Cancer Institute	Seattle	Washington
United States	Northwest Medical Specialties	Tacoma	Washington
United States	H. Moffitt Lee Cancer Center	Tampa	Florida
United States	Scott and White Memorial Hospital (Texas A & M)	Temple	Texas
United States	Kaiser Permanente Medical Center	Vallejo	California
United States	Cancer Center of Kansas	Wichita	Kansas

Sponsors (1)

Lead Sponsor	Collaborator
Geron Corporation

Countries where clinical trial is conducted

United States,  Canada,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	No
Secondary	Objective response	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.	Occurring post randomization through end of study period (8 mos. after the last participant is randomized)	No
Secondary	Time to all-cause mortality	Defined as the time from the date of radomization to death from any cause during the study period.	From the date of randomization through end of study period (8 mos. after the last participant is randomized)	No
Secondary	Safety and tolerability	Safety and tolerability will be assessed by the incidence, nature, and severity of adverse events, laboratory abnormalities, and vital signs.	From the date of randomization through the end of the study period (8 mos. after the last participant is randomized)	Yes