A Phase 2 Study of ASONEP™ to Treat Unresectable and Refractory Renal Cell Carcinoma

• Status: Terminated
• Trial end date: 2015-09-01
• Target enrollment: 0
• Participant gender: All

Summary

This Phase 2a study will investigate the efficacy, safety and tolerability of ASONEP™ (sonepcizumab/LT1009) when administered intravenously once a week, every 4 weeks (or cycle), to subjects with refractory renal cell carcinoma (RCC) until the disease progresses. Subjects who have failed 3 prior treatments for RCC including vascular endothelial growth factor (VEGF) and/or mammalian target of rapamycin (mTOR) inhibitors or who have tumors that cannot be surgically removed will be eligible for screening.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Lpath, Inc.

Criteria

Inclusion Criteria:

• Unresectable, locally advanced recurrent or metastatic RCC

• Histological or cytological confirmation of clear cell RCC - core tissue biopsy of either primary tumor or metastatic lesion with paraffin-embedded tissue specimens if no prior nephrectomy

• Measurable disease by RECIST 1.1

• Had one prior therapy for unresectable RCC with a VEGF/VEGFR targeted therapy (sunitinib, sorafenib, other VEGFR TKI or bevacizumab) - One prior treatment with an mTOR inhibitor (everolimus, temsirolimus or sirolimus) for unresectable disease permitted-Prior immunotherapy (immunomodulators such as cytokines, interleukins, vaccines, etc.) such as IL-2 also permitted

• Male or non-pregnant, non-nursing female

• Life expectancy ≥3 months

• ECOG performance status of 0, 1 or 2

• Must not be receiving any concurrent anticancer therapy

• Baseline CT or MRI scans of measurable disease sites by RECIST 1.1 performed within 2 weeks of Day 0 - For subjects with bone metastases, baseline bone scan performed within 4 weeks of study entry

• Adequate organ and immune function (within 7 days of Day 0):

Hemoglobin >9 g/dL-Absolute neutrophil count >1500 cells/uL without growth factors-Platelet count ≥100x10^9/L without transfusion-Serum creatinine <2.0x ULN or creatinine clearance >40 mL/min-Total bilirubin <1.5x ULN-AST/ALT <2.5x ULN (or <5.0x ULN if liver metastases present)-INR and aPTT <1.5x ULN

• Subject lesions for arterial spin labeling (ASL) MRI ≥2.5cm by CT imaging

• Must understand, be able and willing to fully comply with study procedures

Exclusion Criteria:

• Prior treatment with >3 VEGF pathway and/or mTOR inhibitors for RC cancer

• History of other CNS disease (spinal cord compression, or evidence of symptomatic brain or leptomeningeal carcinomatosis)

• Major surgery within 4 weeks of Day 0

• Radiation therapy within 4 weeks of baseline/infusion. Prior palliative radiation to metastatic lesions is acceptable if there is at least one measurable, non-radiated lesion

• Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection requiring parenteral antibiotics on Day 0

• Known or suspected intolerance or hypersensitivity to study materials or any excipients

• Evidence of bowel obstruction because of theoretical possibility of GI perforation with an anti-angiogenesis agent

• Severe hemorrhage within 4 weeks of screening

• History of GI perforation

• History of non-healing wounds including ulcer or delayed bone fractures

• Prolonged QTc interval on baseline ECG (>450 msec for males or >470 msec for females), cardiac dysrhythmias including atrial fibrillation, torsade de pointes, ventricular tachycardia or fibrillation, pathologic sinus bradycardia (<60 bpm), heart block (excluding 1st degree block, being PR interval prolongation only), congenital long QT syndrome or new ST segment elevation or depression or new Q wave on ECG

• Secondary malignancy within the last 5 years, except for adequately-treated basal cell carcinoma, squamous cell skin cancer, superficial bladder tumors, or in situ cervical cancer

• Previously enrolled in an sonepcizumab study or into this study and subsequently withdrawn

• History of alcohol or other substance abuse within the last year

• Use of corticosteroids or other immunosuppression (if taking systemic steroids [vs. topical], at least 4 weeks must have passed since the last dose)

• Growth factors within 1 week of screening

• Serious medical conditions that might be aggravated by treatment or limit compliance

• Cerebrovascular accident or transient ischemic attack, or pulmonary embolism within 6 months prior to screening

• Participation in another clinical trial

• Other severe or intercurrent acute or chronic medical or psychiatric condition or laboratory abnormality that may increase risk associated with study participation or study drug administration