Due to the subject's lack of conventional treatment options, a treatment plan usingX-PACT administered intra-tumorally is proposed.X-PACT (X-ray Psoralen Activated Cancer Therapy) is comprised of a phosphor device (anenergy modulation agent), methoxsalen sterile solution (a psoralen), X-ray energy andrepresents a potential new approach for the treatment of solid tumors.Methoxsalen is a psoralen found in the seeds of the Ammi majus (Umbelliferae) plant.Importantly, methoxsalen (whether formulated as the sterile solution [Uvadex®] or as ahard gelatin capsule [8-MOP®]) can promote a strong long-term clinical response, asobserved in the treatment of cutaneous T cell lymphoma (CTCL) utilizing extracorporealphotopheresis (ECP) and is approved by the United States Food and Drug Administration [USFDA] for this indication. In ECP, malignant CTCL cells are irradiated with UVA light inthe presence of methoxsalen and then re-administered to the patient.X-PACT may offer the potential for local control of primary or metastatic disease viaadministration of the combination product of methoxsalen and powerful energy converters(Phosphors) when activated by x-ray beam. In addition, there is numerous data in supportof an immunogenic role for activated methoxsalen. The cytotoxic and immunogenic effectsof psoralens are often attributed to psoralen mediated photo-adduct DNA damage [1]. Aprinciple mechanism underlying the long term immunogenic clinical response likely derivesfrom psoralen induced tumor cell cytotoxicity and uptake of the apoptotic cells byimmature dendritic cells, in the presence of inflammatory cytokines [2, 3 4, 5]. However,photochemical modification of proteins and other cellular components can also impact theantigenicity and potential immunogenicity of treated cells [6]. The diversity and potencyof psoralen application is further illustrated by recent success using psoralen in thedevelopment of virus vaccines [7]. The immunogenic activity of methoxsalen supports apotential abscopal effect for X-PACT particularly as it incorporates both radiation andan immunotherapeutic.
Not Provided
Combination Product: X-PACT
X-PACT is comprised of a phosphor device, the drug methoxsalen sterile solution and X-ray
energy. The dose of methoxsalen sterile solution per injection will vary per patient and
will remained fixed across injections within each patient as it is based on the
applicable tumor volume at baseline. Immediately after each injection of the combination
product, patients will be exposed to an X-ray beam delivered via a LINAC (and thus
targeted at the tumor) at a fixed dose to activate the combination product.
Inclusion Criteria:
The patient is willing and able to provide informed consent. Only the patient for whom
this clinical study/experimental treatment was designed will be given the investigational
drug under the treatment of the PI. No other patient is authorized to participate in or
to receive treatment under this treatment protocol.
Exclusion Criteria:
Not applicable
Kimmel Cancer Center at Johns Hopkins at Sibley Memorial Hospital
Washington, District of Columbia, United States
Panagis Galiatsatos, MD
4103672014
pgaliat1@jhmi.edu
Panagis Galiatsatos, MD, Principal Investigator
Johns Hopkins University