OTL38 for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer

• Sponsor: On Target Laboratories, LLC (Industry)
• Overall Status: Completed
• CT.gov ID: NCT03180307
• Collaborator: SynteractHCR (Industry)
• Enrollment: 140
• Locations: 11
• Arms: 2
• Actual Duration (Months): 32.7
• Patients Per Site: 12.7
• Patients Per Site Per Month: 0.4

Study Details

Study Description

Brief Summary

This is a phase 3, randomized, multi-center, single dose, open label, pivotal study in patients diagnosed with, or with high clinical suspicion of, ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery.

Condition or Disease	Intervention/Treatment	Phase
Ovarian Cancer	Drug: OTL38; Device: near infrared camera imaging system; Procedure: laparotomy	Phase 3

Detailed Description

The Phase 3 study is to confirm the efficacy of OTL38 in combination with fluorescent light to detect additional Folate Receptor-positive (FR+) ovarian cancer lesions not detected by palpation and visualization under normal light in patients with FR+ ovarian cancer scheduled to undergo primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Study Design

• Study Type: Interventional
• Actual Enrollment: 140 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: A Phase 3, Randomized, Single Dose, Open-Label Study to Investigate the Safety and Efficacy of OTL38 Injection (OTL38) for Intra-operative Imaging of Folate Receptor Positive Ovarian Cancer
• Actual Study Start Date: Jan 26, 2018
• Actual Primary Completion Date: Apr 16, 2020
• Actual Study Completion Date: Oct 16, 2020

Arms and Interventions

Arm	Intervention/Treatment
Sham Comparator: no fluorescent imaging Patient injected with OTL38, but does not undergo fluorescent imaging	Drug: OTL38; 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes; Other Names: OTL38 for Injection ; Procedure: laparotomy; primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery
Experimental: near infrared imaging arm Patient injected with OTL38 and undergoes near infrared imaging	Drug: OTL38; 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes; Other Names: OTL38 for Injection ; Device: near infrared camera imaging system; Infrared imaging used to excite OTL38 for fluorescence; Other Names: Near IR imaging ; Procedure: laparotomy; primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery

Outcome Measures

Primary Outcome Measures

1. Efficacy Patient Level [30 days]

   Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set)

Secondary Outcome Measures

1. Patient False Positive Rate [30 days]

   False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 85 Years
• Sexes Eligible for Study: Female
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 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 surgical cytoreduction, interval debulking, or have recurrent ovarian cancer 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 for participation in the study 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:

• Previous exposure to OTL38

• Known FR-negative ovarian cancer

• Planned surgical debulking via laparoscopy or robotic surgery, with no intent of laparotomy.

• Patients with known ovarian cancer miliary disease determined preoperatively to be inoperable.

• Any medical condition that, in the opinion of the investigators, could potentially jeopardize the safety of the patient

• History of anaphylactic reactions

• 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), aspartate aminotransferase (AST), alkaline phosphatase (ALP), or total bilirubin.

• Known Stage IV ovarian cancer with brain metastases

• Received an investigational agent in another clinical trial within 30 days prior to surgery

• Known sensitivity to fluorescent light

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	The Mayo Clinic - Phoenix	Phoenix	Arizona	United States	85054
2	University of Arizona	Tucson	Arizona	United States	85724
3	City of Hope Medical Center	Duarte	California	United States	91010
4	University of CA at Irvine Chao Cancer Center	Orange	California	United States	92868
5	Moffitt Cancer Center	Tampa	Florida	United States	33612
6	Karmanos Cancer Institutes	Detroit	Michigan	United States	48201
7	Mayo Clinic-Rochester	Rochester	Minnesota	United States	55905
8	Washington University School of Medicine	Saint Louis	Missouri	United States	63108
9	Kettering Medical Center	Kettering	Ohio	United States	45427
10	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
11	Leiden University Medical Center	Leiden	South Holland	Netherlands	2333 ZA

Sponsors and Collaborators

• On Target Laboratories, LLC
• SynteractHCR

Investigators

• Principal Investigator: Janos Tanyi, MD, University of Pennsylvania

Study Documents (Full-Text)

• Study Protocol - Nov 27, 2018
• Statistical Analysis Plan - May 16, 2017

More Information

Publications

None provided.

• Responsible Party: On Target Laboratories, LLC
• ClinicalTrials.gov Identifier: NCT03180307
• Other Study ID Numbers: OTL-2016-OTL38-006
• First Posted: Jun 8, 2017
• Last Update Posted: Feb 4, 2022
• Last Verified: Jan 1, 2022

• Individual Participant Data (IPD) Sharing Statement: No
• Plan to Share IPD: No
• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: Yes
• Additional relevant MeSH terms: Ovarian Neoplasms; Carcinoma, Ovarian Epithelial

Study Results

Participant Flow

Arm/Group Title	Experimental: OTL38 Injection and Near Infrared Imaging	Sham Comparator: OTL38 Injection and No Fluorescent Imaging
Arm/Group Description	Patient injected with OTL38 and undergoes near infrared imaging. Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes Other Names: OTL38 for Injection Device: near infrared camera imaging system Infrared imaging used to excite OTL38 for fluorescence Other Names: Near IR imaging Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery	Patient injected with OTL38, but does not undergo fluorescent imaging. Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes Other Names: OTL38 for Injection Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery
Period Title: Overall Study
STARTED	134	6
Safety Analysis Set	134	16
Full Analysis Set/ Intent to Image Set	134	0
Per Protocol Analysis Set	106	0
Pharmacokinetic Analysis Set	122	6
COMPLETED	128	6
NOT COMPLETED	6	0

Baseline Characteristics

Arm/Group Title	Experimental: OTL38 Injection and Near Infrared Imaging	Sham Comparator: OTL38 Injection and No Fluorescent Imaging	Total
Arm/Group Description	Patient injected with OTL38 and undergoes near infrared imaging. Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes Other Names: OTL38 for Injection Device: near infrared camera imaging system Infrared imaging used to excite OTL38 for fluorescence Other Names: Near IR imaging Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery	Patient injected with OTL38, but does not undergo fluorescent imaging. Drug: OTL38 0.025 mg/kg of OTL38 in 250ml dextrose 5% in water (D5W) infused intravenously over 60 minutes Other Names: OTL38 for Injection Procedure/Surgery: laparotomy primary surgical cytoreduction, interval debulking, or recurrent ovarian cancer surgery	Total of all reporting groups
Overall Participants	134	6	140
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	60.4 (10.91)	62.8 (21.77)	60.8 (11.39)
Sex: Female, Male (Count of Participants)
Female	134 100%	6 100%	140 100%
Male	0 0%	0 0%	0 0%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	15 11.2%	2 33.3%	17 12.1%
Not Hispanic or Latino	116 86.6%	4 66.7%	120 85.7%
Unknown or Not Reported	3 2.2%	0 0%	3 2.1%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	4 3%	0 0%	4 2.9%
Asian	5 3.7%	1 16.7%	6 4.3%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	7 5.2%	0 0%	7 5%
White	114 85.1%	5 83.3%	119 85%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	4 3%	0 0%	4 2.9%

Outcome Measures

1. Primary Outcome

Title	Efficacy Patient Level
Description	Percentage of patients with at least one evaluable FR+ ovarian cancer lesion confirmed by central pathology (Standard of truth) that was detected using the combination of OTL38 and fluorescent light but not under normal light or palpation (Full Analysis Set)
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Full Analysis Set
Arm/Group Description	Patients exposed to OTL38 and who were randomly assigned to undergo NIR fluorescent imaging (OTL38+imaging) and who: Were evaluated under both normal light and NIR fluorescent light imaging Had central pathology and histology confirmation for at least one FR+ ovarian cancer lesion detected under normal light or NIR fluorescent light imaging
Measure Participants	134
Number (95% Confidence Interval) [percentage of participants]	26.9 20.1%

2. Secondary Outcome

Title	Patient False Positive Rate
Description	False Positive Rate at the patient level (FPRp) will be a major secondary efficacy endpoint and is defined as the percentage of women who underwent both normal light and fluorescent light (Intent-to-Image Set)
Time Frame	30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Full Analysis Set
Arm/Group Description	Patients exposed to OTL38 and who were randomly assigned to undergo NIR fluorescent imaging (OTL38+imaging) and who: Were evaluated under both normal light and NIR fluorescent light imaging Had central pathology and histology confirmation for at least one FR+ ovarian cancer lesion detected under normal light or NIR fluorescent light imaging
Measure Participants	134
Number (95% Confidence Interval) [percentage of participants]	20.2 15.1%

Adverse Events

Time Frame	Incidence rates of treatment-emergent AEs (TEAEs), SAEs, and Adverse Device Effects (ADEs) Visit 1 (screening) through Visit 4 (28 days +/- 7 days).
Adverse Event Reporting Description	The "Other Adverse Events" table captures all drug-related treatment-emergent adverse events reported at or above the frequency threshold for reporting.
Arm/Group Title	Safety Analysis Set
Arm/Group Description	The Safety Analysis Set includes all subjects who received any amount of study drug.
All Cause Mortality
	Safety Analysis Set
	Affected / at Risk (%)	# Events
Total	2/150 (1.3%)
Serious Adverse Events
	Safety Analysis Set
	Affected / at Risk (%)	# Events
Total	22/150 (14.7%)
Blood and lymphatic system disorders
Anaemia	1/150 (0.7%)
Cardiac disorders
Sinus tachycardia	1/150 (0.7%)
Supraventricular tachycardia	1/150 (0.7%)
Gastrointestinal disorders
Abdominal pain	1/150 (0.7%)
Diverticular perforation	1/150 (0.7%)
Gastric perforation	1/150 (0.7%)
Vomiting	1/150 (0.7%)
Hepatobiliary disorders
Cholelithiasis	1/150 (0.7%)
Immune system disorders
Postoperative wound infection	1/150 (0.7%)
Infections and infestations
Septic shock	2/150 (1.3%)
Abscess	1/150 (0.7%)
Clostridium difficile infection	1/150 (0.7%)
Peritonitis	1/150 (0.7%)
Pneumonia	1/150 (0.7%)
Sepsis	1/150 (0.7%)
Injury, poisoning and procedural complications
Postoperative ileus	3/150 (2%)
Anastomotic leak	1/150 (0.7%)
Post procedural haemorrhage	1/150 (0.7%)
Vaginal cuff dehiscence	1/150 (0.7%)
Metabolism and nutrition disorders
Hypoalbuminaemia	1/150 (0.7%)
Hyponatraemia	1/150 (0.7%)
Metabolic acidosis	1/150 (0.7%)
Nervous system disorders
Ischaemic stroke	1/150 (0.7%)
Renal and urinary disorders
Acute kidney injury	3/150 (2%)
Renal impairment	1/150 (0.7%)
Respiratory, thoracic and mediastinal disorders
Pleural effusion	2/150 (1.3%)
Acute respiratory distress syndrome	1/150 (0.7%)
Acute respiratory failure	1/150 (0.7%)
Hypoxia	1/150 (0.7%)
Vascular disorders
Hypotension	1/150 (0.7%)
Hypovolaemic shock	1/150 (0.7%)
Other (Not Including Serious) Adverse Events
	Safety Analysis Set
	Affected / at Risk (%)	# Events
Total	34/150 (22.7%)
Gastrointestinal disorders
Nausea	27/150 (18%)
Vomiting	8/150 (5.3%)
Abdominal pain	7/150 (4.7%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.