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

NCT01762033 | Terminated Phase 2

• 1 other identifier: LT1009-Onc-002
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Renal Cell Carcinoma

Keywords

Renal cell carcinoma; Renal cell cancer; ASONEP; Sonepcizumab

Outcome Measures

Primary Outcomes (1)

• Progression-Free Survival

  The study will use a two-cohort design based on an 8-week PFS rate. Treatment will be considered promising if at least 12 out of the first 22 eligible subjects entered in the Cohort 1 of the study are progression free at Week 8. Enrollment of Cohort 2 will then proceed and be considered worthy of further evaluation if at least 25 out of 39 eligible subjects are progression free at Week 8. If no efficacy signal is observed after enrollment of 22 subjects in Cohort 1, the second cohort will not be enrolled and the clinical study may be stopped.

  8 weeks

Secondary Outcomes (1)

• Safety and Tolerability - Incidence and frequency of adverse events and serious adverse events

  8 weeks

Other Outcomes (4)

• Pharmacokinetics Trough Concentrations

  Pre-dose, weeks 1, 2, 4 of Cycle 1; pre-dose, weeks 2, 4 of Cycle 2

• Tumor Response Rate

  8 weeks

• Changes in Surrogate Markers

  8 weeks

Study Arms (1)

ASONEP

EXPERIMENTAL

ASONEP will be administered by intravenous infusion over 90 minutes at 15 mg/kg once a week every 4 consecutive weeks per cycle

Drug: ASONEP

Interventions

ASONEP DRUG

Intravenous infusion

Also known as: Sonepcizumab, LT1009

ASONEP

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Lpath, Inc.: lead

Study Sites (5)

City of Hope Comprehensive Cancer Center

Duarte, California, 91010, United States

Location

Florida Cancer Specialists

Fort Myers, Florida, 33908, United States

Location

Florida Cancer Specialists

Inverness, Florida, 34453, United States

Location

Medical University of South Carolina

Charleston, South Carolina, 29425, United States

Location

Tennessee Oncology

Nashville, Tennessee, 37203, United States

Location

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

sonepcizumab

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Study Officials

• Susan Hazel

  Lpath, Inc.

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 17, 2012
• First Posted: January 7, 2013
• Study Start: February 1, 2013
• Primary Completion: September 1, 2015
• Study Completion: September 1, 2015
• Last Updated: January 20, 2016

Record last verified: 2016-01

Locations

US (5)