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

NCT02317705 | Completed Phase 2 Results FDA Drug

• 1 other identifier: OTL-2014-OTL38-003
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 4

Brief 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

Conditions

Ovarian Cancer

Outcome Measures

Primary Outcomes (2)

• 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)

• 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)

Study Arms (1)

Patients Receiving OTL38

EXPERIMENTAL

All patients in this arm will receive OTL38 for injection and undergo intraoperative imaging.

Drug: OTL38; Device: Near infrared camera imaging system; Procedure: Laparotomy

Interventions

OTL38 DRUG

Also known as: OTL38 for Injection, CYTALUX™ (pafolacianine) injection

Patients Receiving OTL38

Near infrared camera imaging system DEVICE

Near infrared camera imaging system

Patients Receiving OTL38

Laparotomy PROCEDURE

primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Patients Receiving OTL38

Eligibility Criteria

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

You may qualify if:

• Female patients 18 years of age and older
• 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
• 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
• 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
• 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

You may not qualify if:

• Previous exposure to OTL38
• Known FR alpha-negative ovarian cancer
• Planned surgical approach via laparoscopy or robotic surgery
• Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the patient
• History of anaphylactic reactions or severe allergies
• History of allergy to any of the components of OTL38, including folic acid
• Pregnancy, or positive pregnancy test
• Clinically significant abnormalities on electrocardiogram (ECG)
• Presence of any psychological, familial, sociological or geographical condition potentially hampering compliance with the study protocol and follow-up schedule
• Impaired renal function defined as eGFR\< 50 mL/min/1.73m2
• 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.
• Known Stage IV ovarian cancer with Brain Metastases
• Received an investigational agent in another investigational drug or vaccine trial within 30 days prior to surgery
• Known sensitivity to fluorescent light

Sponsors & Collaborators

• On Target Laboratories, LLC: lead
• SynteractHCR: collaborator

Study Sites (4)

University of CA at Irvine Chao Cancer Center

Orange, California, 92868, United States

Location

Moffitt Cancer Center

Tampa, Florida, 33612, United States

Location

Mayo Clinic-Rochester

Rochester, Minnesota, 55905, United States

Location

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

Related 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;2013(2):CD008765. doi: 10.1002/14651858.CD008765.pub3.

  PMID: 23450588 BACKGROUND

• 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.

  PMID: 21647742 BACKGROUND

• 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.

  PMID: 20065732 BACKGROUND

• 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.

  PMID: 18222534 BACKGROUND

• 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)(Pt 3):855-60. doi: 10.1042/bj2910855.

  PMID: 8387781 BACKGROUND

• 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.

  PMID: 19189636 BACKGROUND

• 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. doi: 10.1016/j.ab.2004.12.026.

  PMID: 15745749 BACKGROUND

• 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. doi: 10.1002/1097-0142(19940501)73:93.0.co;2-s.

  PMID: 7513252 BACKGROUND

• 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.

  PMID: 20613895 BACKGROUND

• 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. doi: 10.1002/(sici)1097-0215(19980417)79:23.0.co;2-v.

  PMID: 9583724 BACKGROUND

• 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-alpha targeting: first in-human results. Nat Med. 2011 Sep 18;17(10):1315-9. doi: 10.1038/nm.2472.

  PMID: 21926976 BACKGROUND

• 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.

  PMID: 1596899 BACKGROUND

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Pafolacianine; Injections; Laparotomy

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Drug Administration Routes; Drug Therapy; Therapeutics; Surgical Procedures, Operative

Results Point of Contact

• Title: Tommy Lee, MSHS, Vice President, Clinical Operations
• Organization: On Target Laboratories

Tlee@ontargetlabs.com

765-588-4547

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

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

Study Record Dates

• First Submitted: November 18, 2014
• First Posted: December 16, 2014
• Study Start: December 1, 2014
• Primary Completion: November 1, 2015
• Study Completion: November 1, 2015
• Last Updated: June 21, 2022
• Results First Posted: June 21, 2022

Record last verified: 2022-05

Locations

US (4)