Single Dose Investigator Initiated Pilot Study to Investigate CYTALUX (Pafolacianine) for Intraoperative Detection of Malignant Tissue in Subjects Undergoing Surgical Resection for Cancer.
For patients and families
In plain language
An automatic summary of structured registry data. It is an orientation aid, not a substitute for the official protocol or a physician assessment.
- What is being studied
- The protocol lists: CYTALUX™ (pafolacianine) injection preoperatively.
- Who it may be relevant to
- Registry conditions: Esophageal Cancer, Gastrointestinal Cancers, Gynecologic Cancers. Basic parameters: from 18 years · All.
- What needs checking
- Age, condition and sex are only basic indicators. Prior treatment, laboratory values and other mandatory requirements appear in the eligibility criteria below.
- Where it takes place
- United States
- Next step
- Save the trial, show it to the treating physician, and confirm current recruitment with the study center. Costs, documents and travel →
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Overview
The goal of clinical trial is to test an FDA approved drug called Pafolacianine that attaches to cancer cells and lights up when seen through a special camera system in adults with a suspected primary diagnosis, or a high clinical suspicion of gastrointestinal, fore gut, pancreatic, hepatobiliary, esophageal malignancies and gyn malignancies planned for HIPEC/debulking, warranting surgery. The main question it aims to answer is: • Can CYTALUX™ (pafolacianine) injection used with near-infrared (NIR) fluorescent imaging improve the detection of malignant tissue in subjects undergoing surgical resection for cancer? Participants taking part in this study will receive the study medication. Then, during the surgery the investigator team will turn on the camera to evaluate if the tumor is visible with the help of the study medication. Taking part in this study will last about 2 months.
Detailed description
Background and Rationale:
Gastroesophageal and pancreatic cancers are aggressive malignancies with limited curative options. Complete surgical resection (R0) remains the cornerstone of curative intent. However, current intraoperative tools-visual inspection, palpation, and endoscopy-are limited in accurately delineating tumor margins and detecting occult lesions. High recurrence rates after surgery suggest a need for improved intraoperative detection techniques.
Folate receptor-alpha (FRα) is overexpressed in a variety of epithelial tumors, including gastric and pancreatic cancers. Recent studies have demonstrated that over one-third of gastric cancers and a subset of peritoneal metastases from gastrointestinal tumors overexpress FRα, making them amenable to targeted imaging. Pafolacianine is a folate analog conjugated to a near-infrared fluorescent dye designed to bind to FRα, enabling real-time intraoperative visualization of cancerous tissue using NIR imaging systems.
Investigational Product:
CYTALUX™ (pafolacianine) is an intravenously administered imaging agent developed by On Target Laboratories, Inc. It consists of OTL0038, a folate analog conjugated to an indole-cyanine green-like dye. The agent selectively binds FRα and emits fluorescence in the NIR spectrum (excitation: 760-785 nm; emission: 790-815 nm), providing high-contrast imaging during surgery.
Mechanism of Action:
Following IV administration, pafolacianine distributes systemically and is cleared rapidly from normal tissues. In FRα-expressing tumor cells, the agent is retained due to receptor-mediated endocytosis. Upon NIR illumination, malignant tissues fluoresce, allowing surgeons to visualize tumors, metastatic nodules, and lymph nodes intraoperatively. This mechanism supports improved tumor localization, identification of positive margins, and enhanced detection of otherwise occult lesions.
Preclinical and Clinical Data:
Preclinical studies in KB human carcinoma cell lines and murine xenograft models have shown high binding affinity to FRα (KD = 10.4 nM) and specific tumor fluorescence. Safety evaluations in rats and dogs demonstrated no phototoxicity or systemic toxicity. Pafolacianine has been evaluated in completed Phase 1, 2, and 3 trials in ovarian and lung cancers (e.g., NCT03180307), where it identified additional malignant lesions or positive margins in 25-40% of patients, reinforcing its clinical utility.
Clinical Need and Future Application:
There is a substantial unmet need for real-time intraoperative tools that enhance surgical decision-making in gastrointestinal oncology. Pafolacianine offers potential benefits in:
Identifying primary and metastatic lesions in gastroesophageal and pancreatic cancer
Assessing peritoneal carcinomatosis in advanced gastric and appendiceal malignancies
Improving accuracy in cytoreductive surgeries and guiding HIPEC decisions
Given the expression profile of FRα in gastrointestinal and other epithelial malignancies, CYTALUX is anticipated to be beneficial for a broader spectrum of tumors beyond ovarian and lung cancers.
Imaging Protocol:
Participants will receive a single IV dose of pafolacianine prior to surgery. NIR imaging will be conducted intraoperatively using a compatible device. Fluorescent lesions will be documented and evaluated for correlation with histopathology. Standard-of-care surgical procedures (e.g., resection, lymphadenectomy) will proceed per usual protocol, supplemented by fluorescent signal guidance.
Endpoints:
Primary: Proportion of additional malignant lesions detected with NIR imaging not identified through standard visualization techniques.
Secondary: Rate of complete (R0) resections, correlation of fluorescence with histologically confirmed malignancy, adverse events related to pafolacianine administration.
Safety Considerations:
CYTALUX has demonstrated a favorable safety profile with no significant toxicity observed in preclinical or clinical settings. The agent is not associated with phototoxicity, and systemic clearance is rapid in non-target tissues.
Interventions
- Drug CYTALUX™ (pafolacianine) injection preoperatively
CYTALUX™ (pafolacianine) injection: folate analog ligand conjugated with an indole cyanine green-like dye as a solution in vials containing 1.6 mL at 2 mg/mL. Each subject will be administered a single intravenous dose of not less than 1 hours before and not more than 24 hours before initiation of intraoperative NIR fluorescent imaging.
Primary outcome measures
- Proportion of subjects with one or more NIR fluorescence positive lesion not detected under normal light and/or palpation [Time frame: Day 1 intra-operatively post intervention]
Secondary outcome measures (1)
- Number of lesions that are simultaneously fluorescence positive and cancer positive [Time frame: Day 1 intra-operatively post intervention]
Eligibility criteria
Inclusion criteria
- Male and Female patients 18 years of age and older
- Have a primary diagnosis, or a high clinical suspicion, of gastrointestinal, fore gut, pancreatic, hepatobiliary, esophageal malignancies and gyn malignancies planned for HIPEC/debulking, warranting surgery.
- Are scheduled to undergo surgical intervention for tumor resection or diagnostic laparoscopy for assessment of disease burden.
- Willingness to stop the use of folate, folic acid, or folate-containing supplements within 48 hours before administration of Cytalux
- Willingness of research participant or legal guardian/representative to give written informed consent.
Exclusion criteria
- Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the subject
- History of anaphylactic reactions to products containing indocyanine green for near infrared imaging. Subjects with a medical history of 'idiopathic anaphylaxis' will require evaluation.
- History of allergy to any of the components of CYTALUX™ (pafolacianine) injection
- Presence of any psychological, familial, sociological condition or geographical challenges potentially hampering compliance with the study protocol or follow-up schedule
Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.
Healthy volunteers: No
Study design
- Allocation
- N/A
- Model
- Single group
- Masking
- Open label
- Primary purpose
- Treatment
Study locations
United States · 1 center
- Clemments University Hospital — Dallas
Identifiers
NCT: NCT07039526 · STU20250049