Phase 2 Study of OTL38 for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer

Ovarian Cancer Clinical Trial

Official title:

A Phase 2, Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection (OTL38) for Intra-operative Imaging of Folate Receptor-alpha Positive Ovarian Cancer

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02317705
• Other study ID #: OTL-2014-OTL38-003
• Status: Completed
• Phase: Phase 2
• Start date: December 2014
• Est. completion date: November 2015

Study information

• Verified date: May 2022
• Source: On Target Laboratories, LLC
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study is being done to:

• test the safety of OTL38

• see if OTL38 helps light up the cancer when viewed with the special camera system

• test the safety of the special camera system for use along with OTL38 during surgery

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: November 2015
• Est. primary completion date: November 2015
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

1. Female patients 18 years of age and older

2. Have a primary diagnosis, or at high clinical suspicion, of primary ovarian cancer (of epithelial type), planned for primary debulking or interval debulking surgery, and:

• Who are scheduled to undergo laparotomy for the debulking surgery OR

• Who are scheduled to undergo laparoscopy and pre-authorized to undergo laparotomy for the debulking surgery, if cancer is detected on the laparoscopy

3. A negative serum pregnancy test at Screening followed by a negative urine pregnancy test on the day of surgery or day of admission for female patients of childbearing potential

4. Female patients of childbearing potential or less than 2 years postmenopausal agree to use an acceptable form of contraception from the time of signing informed consent until 30 days after study completion

5. Ability to understand the requirements of the study, provide written informed consent and authorization of use and disclosure of protected health information, and agree to abide by the study restrictions and to return for the required assessments

Exclusion Criteria:

1. Previous exposure to OTL38

2. Known FR alpha-negative ovarian cancer

3. Planned surgical approach via laparoscopy or robotic surgery

4. Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient

5. History of anaphylactic reactions or severe allergies

6. History of allergy to any of the components of OTL38, including folic acid

7. Pregnancy, or positive pregnancy test

8. Clinically significant abnormalities on electrocardiogram (ECG)

9. Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule

10. Impaired renal function defined as eGFR< 50 mL/min/1.73m2

11. Impaired liver function defined as values > 3x the upper limit of normal (ULN) for alanine aminotransferase (ALT) or aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin.

12. Known Stage IV ovarian cancer with Brain Metastases

13. Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to surgery

14. Known sensitivity to fluorescent light

Related Conditions & MeSH terms

• Carcinoma, Ovarian Epithelial
• Ovarian Cancer
• Ovarian Neoplasms

Intervention

Drug:
• OTL38

Device:
• Near infrared camera imaging system
Near infrared camera imaging system

Procedure:
• Laparotomy
primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Locations

Country	Name	City	State
United States	University of CA at Irvine Chao Cancer Center	Orange	California
United States	University of Pennsylvania	Philadelphia	Pennsylvania
United States	Mayo Clinic-Rochester	Rochester	Minnesota
United States	Moffitt Cancer Center	Tampa	Florida

Sponsors (2)

Lead Sponsor	Collaborator
On Target Laboratories, LLC	SynteractHCR

Country where clinical trial is conducted

United States, 

References & Publications (12)

Al Rawahi T, Lopes AD, Bristow RE, Bryant A, Elattar A, Chattopadhyay S, Galaal K. Surgical cytoreduction for recurrent epithelial ovarian cancer. Cochrane Database Syst Rev. 2013 Feb 28;(2):CD008765. doi: 10.1002/14651858.CD008765.pub3. Review. — View Citation

Crane LM, Arts HJ, van Oosten M, Low PS, van der Zee AG, van Dam GM, Bart J. The effect of chemotherapy on expression of folate receptor-alpha in ovarian cancer. Cell Oncol (Dordr). 2012 Feb;35(1):9-18. doi: 10.1007/s13402-011-0052-6. Epub 2011 Jun 7. Erratum in: Cell Oncol (Dordr). 2012 Jun;35(3):229. — View Citation

Ibeanu OA, Bristow RE. Predicting the outcome of cytoreductive surgery for advanced ovarian cancer: a review. Int J Gynecol Cancer. 2010 Jan;20 Suppl 1:S1-11. doi: 10.1111/IGC.0b013e3181cff38b. Review. — View Citation

Kalli KR, Oberg AL, Keeney GL, Christianson TJ, Low PS, Knutson KL, Hartmann LC. Folate receptor alpha as a tumor target in epithelial ovarian cancer. Gynecol Oncol. 2008 Mar;108(3):619-26. doi: 10.1016/j.ygyno.2007.11.020. Epub 2008 Jan 28. — View Citation

Leamon CP, Low PS. Membrane folate-binding proteins are responsible for folate-protein conjugate endocytosis into cultured cells. Biochem J. 1993 May 1;291 ( Pt 3):855-60. — View Citation

Markert S, Lassmann S, Gabriel B, Klar M, Werner M, Gitsch G, Kratz F, Hasenburg A. Alpha-folate receptor expression in epithelial ovarian carcinoma and non-neoplastic ovarian tissue. Anticancer Res. 2008 Nov-Dec;28(6A):3567-72. — View Citation

Parker N, Turk MJ, Westrick E, Lewis JD, Low PS, Leamon CP. Folate receptor expression in carcinomas and normal tissues determined by a quantitative radioligand binding assay. Anal Biochem. 2005 Mar 15;338(2):284-93. — View Citation

Ross JF, Chaudhuri PK, Ratnam M. Differential regulation of folate receptor isoforms in normal and malignant tissues in vivo and in established cell lines. Physiologic and clinical implications. Cancer. 1994 May 1;73(9):2432-43. — View Citation

Shih KK, Chi DS. Maximal cytoreductive effort in epithelial ovarian cancer surgery. J Gynecol Oncol. 2010 Jun;21(2):75-80. doi: 10.3802/jgo.2010.21.2.75. Epub 2010 Jun 30. — View Citation

Toffoli G, Russo A, Gallo A, Cernigoi C, Miotti S, Sorio R, Tumolo S, Boiocchi M. Expression of folate binding protein as a prognostic factor for response to platinum-containing chemotherapy and survival in human ovarian cancer. Int J Cancer. 1998 Apr 17;79(2):121-6. — View Citation

van Dam GM, Themelis G, Crane LM, Harlaar NJ, Pleijhuis RG, Kelder W, Sarantopoulos A, de Jong JS, Arts HJ, van der Zee AG, Bart J, Low PS, Ntziachristos V. Intraoperative tumor-specific fluorescence imaging in ovarian cancer by folate receptor-a targeting: first in-human results. Nat Med. 2011 Sep 18;17(10):1315-9. doi: 10.1038/nm.2472. — View Citation

Weitman SD, Lark RH, Coney LR, Fort DW, Frasca V, Zurawski VR Jr, Kamen BA. Distribution of the folate receptor GP38 in normal and malignant cell lines and tissues. Cancer Res. 1992 Jun 15;52(12):3396-401. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Sensitivity of OTL38 in Detecting Folate Receptor-alpha Positive Ovarian Cancer During Surgery.	Sensitivity for the detection of folate receptor-alpha positive (FRAP) ovarian cancer lesions is defined as the ratio (multiplied by 100) of the number of FRAO ovarian cancer lesions confirmed by both fluorescent light and the pathology/ and immunohistochemistry lab (TP) over the number of FRAP ovarian cancer lesions confirmed by the pathology/ and immunohistochemistry lab (TP+FN). 95% lower one-sided confidence interval was used.	Day of Surgery (Day 1)
Primary	Positive Predictive Value (PPV) of OTL38 in Detecting Folate Receptor-alpha Positive Ovarian Cancer During Surgery.	PPV for the detection of FRAP ovarian cancer lesions is defined as the ratio (multiplied by 100) of the number of FRAP ovarian cancer lesions confirmed by both fluorescent light and the pathology/ and immunohistochemistry lab (TP) over the number of FRAP ovarian cancer lesions confirmed by fluorescent light (TP + FP).; 95% lower one-sided confidence interval was used.	Day of Surgery (Day 1)