A Randomized Phase II Study of Imetelstat as Maintenance Therapy After Initial Induction Chemotherapy for Advance Non-small Cell Lung Cancer(NSCLC)
- 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
- 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
- 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
- Males must agree to use effective birth control for themselves or their partner
during and for 12 weeks after the last treatment with imetelstat.
Patients who meet any of the following criteria will be excluded from screening and study
- Patients who are not eligible for induction therapy with a platinum based
- Patients who have received, or are scheduled to receive pemetrexed or erlotinib as
- 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
- 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
- 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.