Intratumoral PH-762 for Skin Cancer
Recruiting in Palo Alto (17 mi)
+6 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Phio Pharmaceuticals Inc.
Must not be taking: Chemotherapy, Radiation, Immunotherapy, others
Disqualifiers: Other malignancy, Auto-immune disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?This trial tests PH-762 injections in adults with certain skin cancers. The treatment helps the immune system recognize and fight the cancer by stopping it from hiding. Patients will receive injections over a period of weeks.
Will I have to stop taking my current medications?
The trial does not specify if you need to stop taking your current medications, but you cannot be on current cancer treatments like chemotherapy, radiation, or immunotherapy.
What makes the drug PH-762 unique for treating skin cancer?
PH-762 is unique because it is administered directly into the tumor (intratumoral), which may enhance its effectiveness by targeting the cancer cells more precisely compared to other treatments that are applied systemically or topically.
12345Eligibility Criteria
This trial is for adults with certain skin cancers: squamous cell carcinoma, melanoma, or Merkel cell carcinoma. They must have at least one tumor between 1 and 3 cm that can be injected and removed surgically. People with other recent cancers, current cancer treatments, serious medical conditions like auto-immune diseases, or who are pregnant/breastfeeding cannot join.Inclusion Criteria
I have been diagnosed with a specific type of skin cancer.
I have a tumor between 1.0 cm and 3.0 cm that can be reached for treatment.
Exclusion Criteria
I have not had any other cancer in the last 3 years, with some exceptions.
I do not have any serious illnesses that could worsen by joining this study.
I am not pregnant or breastfeeding.
+1 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Participants receive four intratumoral injections of PH-762 at weekly intervals into a single tumor, followed by surgical removal of the tumor approximately two weeks after the last injection
6 weeks
4 visits (in-person)
Follow-up
Participants are monitored for safety and effectiveness after treatment
11 weeks
Participant Groups
The trial tests PH-762's safety by giving participants four weekly injections directly into a single tumor on the skin. After these injections, the treated tumor will be surgically removed to study how it responded to PH-762 and what happens to the drug in the body.
1Treatment groups
Experimental Treatment
Group I: Sequential escalating doses of PH-762.Experimental Treatment1 Intervention
Escalating doses of PH-762 are to be tested, with an observation period between doses.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
UPMC Department of DermatologyPittsburgh, PA
Paradigm Clinical ResearchSan Diego, CA
Phio Pharmaceuticals Corp.Marlborough, MA
Banner MD Anderson Cancer CenterGilbert, AZ
More Trial Locations
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Who Is Running the Clinical Trial?
Phio Pharmaceuticals Inc.Lead Sponsor
Prosoft ClinicalCollaborator
References
Photodynamic therapy and fluorescence diagnosis of skin cancers. [2019]In several countries throughout the world the photosensitizer porfimer-sodium has been approved for systemic photodynamic therapy (PDT) for different oncological indications. However, owing to the prolonged photosensitization entailed, the use of this porphyrin derivative is restricted. Currently, the most promising sensitizers in dermatology that can be applied topically are 5-aminolevulinic acid (ALA) or ester derivatives that are precursors of heme biosynthesis. ALA has shown good clinical and excellent cosmetic results in superficial skin cancer and precancerous conditions, e.g. superficial basal cell carcinoma (BCC), or actinic keratoses (AK): phase III studies have demonstrated its efficacy especially in Bowen's disease and AK. ALA-PDT for AK was therefore approved by the FDA in late 1999, and the corresponding registration process is currently in train in Europe. Besides its usefulness in oncological therapy, ALA also has a unique feature that can be exploited for diagnostic purposes: after topical or systemic application protoporphyrin IX is induced rather selectively in epithelial tumors, with a high tumor-to-surrounding tissue ratio, which can be visualized after excitation with light. By using a CCD camera system together with digital imaging, the contrast of the acquired fluorescence images can be significantly enhanced and allows the determination of a threshold, which can be utilized either for a directed biopsy or for preoperative planning when Mohs' surgery is scheduled. At present, the routine employment of such systems is being assessed in prospective studies.
pH effects on the cellular uptake of four photosensitizing drugs evaluated for use in photodynamic therapy of cancer. [2019]The difference in extracellular pH in malignant as compared to normal healthy tissues has been proposed to contribute to selective uptake of photosensitizers in tumors. Hematoporphyrin IX (HpIX), disulfonated meso-tetraphenylporphine (TPPS(2a)), meso-tetra(3-hydroxyphenyl)porphine (mTHPP) and meso-tetra(3-hydroxyphenyl)chlorin (mTHPC) were chosen to examine the pH dependence of their cellular drug uptake. The study was performed in the pH range 6.5-8.0 and showed that significantly higher amounts of the drug are taken up by T-47D cells at low pH values only in the case of HpIX. The pH value of the incubation medium did not influence the cellular uptake of mTHPP, mTHPC and TPPS(2a) significantly. The present work indicates that tumor selectivity of dyes, which get more lipophilic with decreasing pH value, may be related to the low extracellular pH value.
Comparison of photosensitizers in saline and liposomes for tumor photodynamic therapy and skin phototoxicity. [2013]The uptake and distribution, skin phototoxicity, and direct tumor ablative potential of three porphyrin photosensitizers: hematoporphyrin derivative (HPD), dye hematoporphyrin ether (DHE), polyhematoporphyrin esters (PHE), and of Rhodamine-123 (Rh-123) have been studied in the AJ-CR inbred albino female mouse implanted with C-1300 neuroblastoma. Photosensitizer delivery was studied using saline and liposome carriers. The ratio of tumor uptake of the porphyrin compounds compared to the tumor-bed musculature and skin was favorable with both saline and liposome delivery. Rhodamine-123 precipitated in saline but was delivered effectively throughout the body in liposomes. There was no selective uptake by tumor cells of Rh-123 in this tumor model. Skin phototoxicity with the porphyrin compounds was mildly decreased using liposomes carriers while Rh-123 demonstrated no skin phototoxicity. DHE had the greatest tumoricidal effect among the porphyrin compounds. PHE has the potential of increased effect due to the ability to use higher light dosages in the activation of this porphyrin. Rhodamine-123 had no tumor effect in this animal model. Clinical implications of phototherapy with these four compounds are addressed.
Determination of the maximal carcinoma/normal skin ratio after HpD or m-THPC administration in Hairless mice (SKH-1) by fluorescence spectroscopy. [2019]The two major steps in our study on the treatment of skin carcinomas by photochemotherapy (PCT) were the development of a skin tumor model in Hairless mice by a chemical carcinogenesis and the use of fluorescence spectroscopy, a semi-quantitative and non-invasive method, in order to determine the time after i.p. injection of photosensitizer when the tumor/normal skin ratio was the highest. A three-step carcinogenesis protocol provided mice bearing carcinomas and these were used to determine the tumor/normal skin ratios of two photosensitizers by fluorescence spectroscopy. Hematoporphyrin derivative (HpD) (5 mg/kg body weight) and m-tetra(hydroxyphenyl) chlorine (m-THPC) (0.3 mg/kg body weight) were injected i.p., and fluorescence was measured at 1, 4, 8, 12, 24, 48, 72 and 96 h after injection. The best carcinoma/normal skin ratio would be 3.2+/-1.4 for HpD and 2.7+/-2.1 for m-THPC, respectively. The delays required to reach these ratios were 72 h for HpD and 24 h for m-THPC. These results have to be considered with caution due to the high SEs and they must be confirmed by organic extraction. Photodynamic therapy with the same doses of HpD and m-THPC used in this pharmacokinetic study has to be carried out in order to compare the toxicities of the two photosensitizers and to determine which one is the best for this type of tumor.
Phthalocyanine-based photosensitizer with tumor-pH-responsive properties for cancer theranostics. [2020]Photodynamic therapy (PDT) has attracted attention for its potential for tumor destruction. We herein report a pH-responsive photosensitizer, synthesized by conjugating zinc phthalocyanine (ZnPc) with 2,4,6-tris(N,N-dimethylaminomethyl) phenoxy (TAP), which exhibited high phototoxicity at pH 6.5 (slightly acidic condition as in the extracellular tumor microenvironment) but no obvious phototoxicity at physiological pH 7.4. This pH-responsive photosensitizer specifically destroyed mouse mammary carcinoma cells 4T1 with an IC50 of 0.20 μM under a relatively low light dosage (2.5 J cm-2). The subsequent in vivo studies using 4T1-bearing mice demonstrated that this tumor-targeting photosensitizer ZnPc(TAP)4 not only ablated tumor cells photodynamically but also presented clear fluorescence cell imaging of tumor sites. These findings suggest that such a tumor-pH-responsive photosensitizer based on phthalocyanine may open up a new avenue for tumor-targeted and image-guided cancer theranostics in PDT.