Cathepsin Activatable Fluorescent Probe (LUM015)

A Phase I Study of the Safety and Activation of a Cathepsin-Activatable Fluorescent Cancer Specific Probe LUM015

Real-time detection of cancer cells during surgical removal of a tumor is important. Currently when tissue is removed at the time of surgery, the removed tissue goes to pathology when the margins (edges of the tissue) are examined to see if cancer cells are present. This may take a few to several days. Patients tissue with positive (cancer cells present) margins may require additional therapies including surgery. The purpose of this study is to determine a safe dose of a new imaging agent (LUM015), like a fluorescent contrast agent or dye, that will show in the tumor area during surgery and may help facilitate visualization of tumor for its removal.

Study Overview

• Status: Completed
• Conditions: Sarcoma; Soft Tissue Sarcoma; Breast Cancer
• Intervention / Treatment: Drug: LUM015

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 1

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27710
      • Duke University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 74 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 18 years of age or older
• Diagnosis of soft tissue sarcoma and breast cancer patients scheduled for a lumpectomy or mastectomy.
• Subjects must be scheduled for surgical resection of a tumor at least 1 cm in size.
• Performance status of 0 or 1
• Able to read, understand and sign an informed consent form
• Must be able and willing to follow study procedures and instructions including a possible overnight stay before surgery
• Otherwise healthy except for the diagnosis of cancer
• ALT, AST, and total bilirubin within 1.5x institutional upper normal limits; and alkaline phosphatase within 2.5x institutional upper normal limits
• Serum creatinine of 1.5 mg or less; creatinine clearance greater than 30 ml/min
• May have previously received pre-operative external beam radiation therapy for this sarcoma

Exclusion Criteria:

• Pregnant or lactating
• Prolonged QT interval: corrected QT interval (QTc) > 480 msec
• Insulin dependent diabetes
• History of anaphylactic reactions to any drug or contrast agent
• Asthma under medical management
• Uncontrolled high blood pressure
• Severe, active co-morbidity
• Known substance addiction
• Sexually active and not willing/able to use medically acceptable forms of contraception.
• Obesity defined as BMI as body mass index greater than 35 kg/meter squared.
• Atopy or atopic syndrome
• Known AIDS
• Cannot have taken an investigational drug within 30 days of coming onto this study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: DIAGNOSTIC
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: LUM015; Receive single dose of LUM015 through a vein in the arm the day prior to surgery	Drug: LUM015; LUM015 assigned dose given once by IV push

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Dose of LUM015 in mg	Dose of LUM015 in mg that is tolerated and labels tumors	24 hours

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mean number of fluorescence counts per second per square centimeter		At time of surgery
To obtain PK/PD information regarding LUM015 when administered IV in patients.	The pharmacokinetic parameters to be measured will include: area under the curve (AUCt), maximum concentration (Cmax), time to maximum concentration (tmax) and first-order terminal (elimination) rate constant. Secondary (derived) parameters will include: terminal half-life (t1/2), clearance (CL), mean residence time (MRT), and apparent volume of distribution during the terminal phase (Vz). The distribution of these parameters will be described for each dose cohort separately; breast and sarcoma patients will be combined.	Two years
To analyze cathepsin protease expression in tumors.	Cathepsin expression in tumors, measured in arbitrary units by Real-Time PCR compared to adjacent normal tissue when available, will be assessed in sarcomas and breast tumors. For each tissue specimen the expression of cathepsin will be compared to the imaging signal. Scatterplots of cathepsin level against imaging signal will be made according to tissue type within each dose cohort.	2 Years

Collaborators and Investigators

• Sponsor: David Kirsch
• Collaborators: American Society of Clinical Oncology
• Investigators: Principal Investigator: Brian Brigman, MD, Duke University

Study record dates

Study Major Dates

• Study Start: June 1, 2012
• Primary Completion (ACTUAL): August 1, 2014
• Study Completion (ACTUAL): August 1, 2015

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: June 20, 2012
• First Posted (ESTIMATE): June 22, 2012

Study Record Updates

• Last Update Posted (ESTIMATE): December 9, 2015
• Last Update Submitted That Met QC Criteria: December 8, 2015
• Last Verified: December 1, 2015

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms, Connective and Soft Tissue; Neoplasms by Histologic Type; Neoplasms; Sarcoma
• Other Study ID Numbers: Pro00035444