Intraoperative Folate Targeted Fluorescence in Renal Cell Carcinoma

Primary

• To explore the use of OTL38 and fluorescence imaging to detect RCC in partial nephrectomy at the margins of resection, and in lymph node(s) or other metastases during radical nephrectomy.

Study Overview

• Status: Completed
• Conditions: Renal Cell Carcinoma
• Intervention / Treatment: Drug: OTL38; Device: Intraoperative fluorescence imaging system

Detailed Description

Administration of the study drug, OTL38, will begin prior to skin incision in the preoperative area where safety monitoring will occur. The tumor resection occurs approximately 2 hours after being brought back to the operating room and so there is no wait time between infusion and being taken back to operating room. Intraoperative fluorescent imaging will be utilized in parallel with the standard operating procedure to capture images during surgery. Images also will be taken of the excised specimen on the back table. The excised specimen will be sent to the pathology department for fluorescent imaging and immunohistochemistry for FR. Subjects will have a 2-5 day hospital stay (normal nephrectomy recovery period) where safety measurements will be taken. Final safety measurements will be taken at the 10-day and 1-month follow-up visits.

• Study Type: Interventional
• Enrollment (Actual): 14
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Indiana
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Melvin and Bren Simon Cancer Center
    • Indianapolis, Indiana, United States, 46202
      • Indiana University Health Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria for localized RCC treated with partial nephrectomy

To be considered eligible to participate in this study, a patient must meet all the inclusion criteria listed below:

• ≥ 18 years of age.
• Have primary or suspected diagnosis of RCC, with presence of cT1-2 renal mass by diagnostic CT assessment.
• Scheduled for partial nephrectomy of renal mass.
• Expected survival of at least 3 months.
• Written informed consent available.
• ECOG ≤ 1 (Appendix G).
• Negative serum or urine pregnancy test within 24 hours for females of child bearing age
• Recovered from toxicity of any prior therapy to ≥ grade 1.

Inclusion criteria for advanced RCC treated with radical nephrectomy

To be considered eligible to participate in this study, a patient must meet all the inclusion criteria listed below:

• ≥ 18 years of age.
• Have pathologic or suspected diagnosis of RCC with presence of cT1-4 renal mass and evidence of nodal or metastatic involvement by diagnostic CT assessment
• Scheduled for radical nephrectomy and lymph node dissection.
• Expected survival of at least 3 months.
• ECOG ≤ 2.
• Negative serum or urine pregnancy test within 24 hours for females of child bearing age.
• Recovered from toxicity of any prior therapy to ≥ grade 1
• Written informed consent available.

Exclusion criteria for both localized and advanced RCC

• History of any anaphylactic reaction, any severe allergy, or any allergy to folate.
• Brain metastases
• Baseline GFR < 50 mL/min/1.73m2)
• Hepatic toxicity ≥ Grade 2 (using CTCAE version 4 standard definitions).
• Participation in another investigational drug trial either concurrently or 30 days prior to surgery
• Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient, limit the patient's ability to complete the study, and/or compromise the objectives of the study.
• Known sensitivity to fluorescent light

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Partial nephrectomy; OTL38 will be given approximately 2 hours before surgery. Intraoperative fluorescent imaging will utilized in parallel with standard operating procedures for partial nephrectomy. Photographs of the surgery field and tumor (ex-vivo) will be taken under normal light and fluorescent light.	Drug: OTL38; OTL38 is a folate analog conjugated with a fluorescent dye that emits light in the near infrared spectrum. This longer wavelength allows for deeper penetration of the fluorescent light through tissues with the potential to better image tumors beneath adipose tissue or deeper into organ parenchyma.; Device: Intraoperative fluorescence imaging system
Experimental: Radical nephrectomy; OTL38 will be given approximately 2 hours before surgery. Intraoperative fluorescent imaging will utilized in parallel with standard operating procedures for radical nephrectomy. Photographs of the surgery field and tumor (ex-vivo) will be taken under normal light and fluorescent light.	Drug: OTL38; OTL38 is a folate analog conjugated with a fluorescent dye that emits light in the near infrared spectrum. This longer wavelength allows for deeper penetration of the fluorescent light through tissues with the potential to better image tumors beneath adipose tissue or deeper into organ parenchyma.; Device: Intraoperative fluorescence imaging system

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Presence of Fluorescence of cT1 RCC in Partial Nephrectomy Specimens	Pathology results will be compared with immunohistochemistry results for each patient. Fluorescence will be looked for in the margins of resection for partial nephectomy and in regional lymph nodes and metastases for radical nephrectomy.	During procedure, an average of 2 hours

Collaborators and Investigators

• Sponsor: Chandru Sundaram
• Investigators: Principal Investigator: Chandru P. Sundaram, MD, Indiana University School of Medicine, Indiana University Simon Cancer Center

Study record dates

Study Major Dates

• Study Start (Actual): December 29, 2015
• Primary Completion (Actual): March 20, 2018
• Study Completion (Actual): April 2, 2019

Study Registration Dates

• First Submitted: December 8, 2015
• First Submitted That Met QC Criteria: December 30, 2015
• First Posted (Estimate): January 1, 2016

Study Record Updates

• Last Update Posted (Actual): February 25, 2020
• Last Update Submitted That Met QC Criteria: February 16, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Imaging; Partial nephrectomy; Radical nephrectomy; Fluorescence
• Additional Relevant MeSH Terms: Neoplasms by Histologic Type; Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Adenocarcinoma; Neoplasms, Glandular and Epithelial; Kidney Neoplasms; Carcinoma, Renal Cell; Carcinoma
• Other Study ID Numbers: IUSCC-0546