A Randomized, Phase 2, Study to Assess the Safety and Activity of CRLX101, a Nanoparticle Formulation of Camptothecin, in Patients With Advanced Non-Small Cell Lung Cancer Who Have Failed One or Two Previous Regimens of Chemotherapy
- Male or female patients who are ≥ 18-years of age.
- Histologically or cytologically confirmed, locally advanced or metastatic NSCLC
(adenocarcinoma, bronchoalveolar, squamous cell, large cell, or mixed carcinoma) that
is not amendable to surgical treatment and patient has have failed 1 or 2 different
lines of chemotherapy.
- Measureable disease and evidence of progression on the previous therapy. Progression
may be clinical or radiological.
- ECOG performance status of 0 or 1.
- Life expectancy of at least 3 months.
- Hemoglobin ≥ 10 g/dL.
- Absolute neutrophil count (ANC) ≥ 1500 cells/µL without growth factor support.
- Platelet count ≥ 100,000 cells/µL without support.
- Adequate hepatic and renal function including the following: Total bilirubin < 2 ×
ULN, AST or ALT ≤ 2.5 × ULN or ≤ 5 × ULN for patients with liver metastasis, PTT
within normal limits, INR ≤ 1.5, Serum Creatinine <1.5 ULN
- At least 4 weeks post any radiotherapy or biological therapy; at least 6 weeks post
- Full recovery from diagnostic or therapeutic surgery (i.e., complete wound healing)
and at least 30 days have elapsed prior to initial dosing.
- Full recovery from the toxic effects of prior therapy (i.e., Common Toxicity Criteria
[CTC] Grade 1 or less with the exception of Grade 2 alopecia).
- Women of childbearing potential must have adequate pregnancy test. If
postmenopausal, must be ≥ 12 months since last menses.
- Women of childbearing potential and men must agree to use an effective form of
contraception during the study and for 60 days after the last dose of study drug.
- CNS metastases by radiologic evidence or histology, unless clinically stable (must
have been treated by resection or radiation) for at least 4 weeks prior to first dose
of study drug. Patients may not be receiving dexamethasone for control of CSF
- Concurrent therapeutic anticoagulation: PTT less than or equal to 1.5 × ULN or low
dose aspirin and low-weight heparin only are allowed.
- More than 2 previous lines of chemotherapy for lung cancer. This includes biologic
- History of previous cerebrovascular accident (CVA) or history transient ischemic
attack (TIA) within 6 months of study entry.
- History of prior malignancy not cured by excision. Patients with non-melanoma skin
cancer or carcinoma in situ of the cervix are not excluded, but patients with other
prior malignancies must have had at least 2-year disease free interval.
- Recent history (within 6 months of screening) of unstable angina, myocardial
infarction, or NYHA Class III or IV congestive heart failure
- History of cardiac arrhythmia requiring medical or electrical therapy.
- QTc > 450 msec for males and > 470 msec for females.
- Any major surgery within 30 days or minor surgery within 10 days of study entry, or
patient not recovered from surgery.
- History of organ or bone marrow transplant.
- Known active and/or uncontrolled infection, including HIV and are not stable on
- Any investigational therapy within 28 days of study entry.
- Pregnant or nursing.
- Anyone who in the judgment of the investigator cannot comply with the protocol,
provide truly informed consent, or is likely to live < 90 days
- Severe or significant allergy to any chemotherapy or premedication.
- Clinically evident ascites (e.g., abdominal distention, bulging and/or fluid wave) or
Grade 3 peripheral edema.
- Any prior cancer treatment with a topoisomerase I inhibitor.