Safety and Feasibility of Intraoperative Visualization With Cytalux in Children

A Pilot Study of Near-Infrared Imaging Using the Novel Imaging Agent Cytalux for Adolescent Patients With Metastatic Osteosarcoma Undergoing Pulmonary Metastasectomy

Pediatric subjects aged 6-17 with biopsy confirmed cancer and imaging findings suspicious for pulmonary metastatic disease scheduled to undergo pulmonary metastasectomy via and open or minimally invasive approach.

Pulmonary metastasectomy, or surgery to remove cancer which has spread to the lungs, plays a key role in the treatment of children with metastatic solid tumors. Fluorescence-guided surgery (FGS) has been shown to be a promising technique to highlight cancer cells and enable real-time surgical guidance (Stummer 2006, Hernot 2019, Goldstein 2021). Current techniques for fluorescence-guided surgery rely on indocyanine green (ICG), a non-specific fluorescent molecular agent which tends to accumulate in cancer cells because of increased angiogenesis and decreased lymphatic clearance. Molecular agents targeted to tumor-specific receptors offer the hope of increased sensitivity and specificity for detecting even very small metastatic nodules, and thus enhancing surgical clearance of disease.

Many of the tumors which metastasize to the lung are known to express the folate receptor and may therefore benefit from utilizing the tumor imaging agent CYTALUX (pafolacianine). CYTALUX (Pafolacianine) as a diagnostic tool during cancer resection has already been investigated in adults (approved NDA 214907), and no age-specific differences are expected in the pediatric population. Findings from the ELUCIDATE trial in adults demonstrated that intraoperative molecular imaging with CYTALUX (pafolacianine) improves surgical outcomes by identifying occult tumors and close surgical margins and it therefore gained FDA approval for adults with cancer in the lung (both primary and metastatic) as an adjunct with near infrared (NIR) imaging for detection of disease during surgery. We anticipate that this agent will have similar safety and efficacy in children and to similarly demonstrate applicable for all types of metastatic tumors.

This is a pilot study in pediatric subjects aged 6-17 with biopsy confirmed cancer and imaging findings suspicious for pulmonary metastatic disease scheduled to undergo pulmonary metastasectomy via an open or minimally invasive approach.

In the proposed study, subjects and their parents or guardians will give informed consent prior to commencement of any study procedures. Subjects will be dosed with 0.025 mg/kg CYTALUX (pafolacianine) injection intravenously from 4 hours to up to 24 hours prior to surgery. Subjects will be considered evaluable if they are exposed to study drug and/or NIR fluorescent light imaging. During surgery, all subjects will first undergo evaluation by normal surgical techniques (white light, palpation, and/or other localization techniques) and all suspicious nodules and lesions identified under standard surgical approach will be recorded as such. Following standard surgical assessment, subjects will undergo assessment with NIR fluorescent light imaging prior to and after resection.

Inclusion Criteria:

1. Patients 6-17 years of age at the time of study enrollment
2. Willingness of research participant or legal guardian/representative to give written informed consent
3. Willingness of patients (subjects) age 12-17 to provide written adolescent assent
4. Patient weight greater than or equal to 20 kg
5. Histologically confirmed diagnosis of osteosarcoma, synovial sarcoma, hepatoblastoma, rhabdomyosarcoma, Ewing sarcoma, Wilms tumor or other non-rhabdomyosarcoma soft tissue sarcoma
6. Imaging findings highly suspicious for pulmonary metastatic disease based on CT, PET-CT or other imaging and warranting pulmonary surgery based on the judgment of the treating team. At least one nodule ≥4mm measured by preoperative imaging.
7. Female (assigned female at birth) participant is not pregnant and agrees to an acceptable form of contraception from the time of consent through 30 days after study intervention. Confirmed abstinence is an acceptable form of contraception.
8. Female (assigned female at birth) participant must agree to not donate ova from time of consent until 30 days after study intervention
9. Male (assigned male at birth) participant must agree to not donate sperm from time of consent until 30 days after study intervention.

Exclusion Criteria:

1. Any medical condition that in the opinion of the investigators could potentially jeopardize the safety of the subject
2. History of anaphylactic reactions to products containing indocyanine green for near infrared imaging. Subjects with a medical history of 'idiopathic anaphylaxis' will also be excluded.
3. History of allergy to any of the components of CYTALUX™ (PAFOLACIANINE) INJECTION
4. Presence of any psychological, familial, sociological condition or geographical challenges potentially hampering compliance with the study protocol or follow-up schedule
5. Impaired renal function defined as eGFR< 50 mL/min/1.73m2
6. 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 >2x ULN for total bilirubin except in subjects with Gilbert's syndrome.
7. Patient unable or unwilling to discontinue folate, folic acid, or folate-containing supplements 48 hours before study drug administration
8. History of drug-related serious adverse event with prior Cytalux administration will be an exclusion for re-enrollment for contralateral surgery (see section 5.7).
9. Participants will be excluded if their 12th or 18th birthday would occur during study participation
10. Male sex at birth and commitment to acceptable form of contraception from time of consent through 30 days after study intervention with confirmed abstinence as an acceptable form of contraception as an inclusion criterion.