Cathepsin Activatable Fluorescent Probe (LUM015)

• ClinicalTrials.gov Identifier: NCT01626066
• Recruitment Status: Completed
• First Posted: June 22, 2012
• Last Update Posted: December 9, 2015
• Sponsor: David Kirsch
• Collaborator: American Society of Clinical Oncology
• Information provided by (Responsible Party): David Kirsch, Duke University

Tracking Information

• First Submitted Date: June 20, 2012
• First Posted Date: June 22, 2012
• Last Update Posted Date: December 9, 2015
• Study Start Date: June 2012
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: June 20, 2012)

Dose of LUM015 in mg [ Time Frame: 24 hours ]

Dose of LUM015 in mg that is tolerated and labels tumors

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: October 21, 2013)

• Mean number of fluorescence counts per second per square centimeter [ Time Frame: At time of surgery ]
• To obtain PK/PD information regarding LUM015 when administered IV in patients. [ Time Frame: Two years ]
  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.
• To analyze cathepsin protease expression in tumors. [ Time Frame: 2 Years ]
  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.

• Original Secondary Outcome Measures (submitted: June 20, 2012): Mean number of fluorescence counts per second per square centimeter [ Time Frame: At time of surgery ]
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Cathepsin Activatable Fluorescent Probe
• Official Title: A Phase I Study of the Safety and Activation of a Cathepsin-Activatable Fluorescent Cancer Specific Probe LUM015
• Brief Summary: 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.
• Detailed Description: Not Provided
• Study Type: Interventional
• Study Phase: Phase 1
• Study Design: Allocation: N/A; Intervention Model: Single Group Assignment; Masking: None (Open Label); Primary Purpose: Diagnostic

Condition

• Sarcoma
• Soft Tissue Sarcoma
• Breast Cancer

Intervention

Drug: LUM015

LUM015 assigned dose given once by IV push

Study Arms

Experimental: LUM015

Receive single dose of LUM015 through a vein in the arm the day prior to surgery

Intervention: Drug: LUM015

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: June 20, 2012): 15
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: August 2015
• Actual Primary Completion Date: August 2014 (Final data collection date for primary outcome measure)

Eligibility Criteria

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 74 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: United States

Administrative Information

• NCT Number: NCT01626066
• Other Study ID Numbers: Pro00035444
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Responsible Party: David Kirsch, Duke University
• Study Sponsor: David Kirsch
• Collaborators: American Society of Clinical Oncology

Investigators

• Principal Investigator: Brian Brigman, MD; Duke University

• PRS Account: Duke University
• Verification Date: December 2015