Padeliporfin VTP for Lung Cancer
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
Sponsor: Impact Biotech Ltd
Must not be taking: Anticoagulants, Antiplatelets, Antibiotics, others
Disqualifiers: Pregnancy, Heart failure, Hypoxia, others
No Placebo Group
Approved in 1 Jurisdiction
Trial Summary
What is the purpose of this trial?Phase 1/1b, safety, feasibility, and light dose titration study followed by further study of therapeutic ablation effects.
Patients with high risk of peripheral primary lung cancer, stage 1A1/1A2, for whom surgical treatment is planned, will be recruited. Surgery will be performed at 5-21 days following the VTP procedure.
Study intervention: robotic assisted bronchoscopic Padeliporfin VTP lung ablation: vascular targeted photodynamic therapy using Padeliporfin photosensitizer.
Do I have to stop taking my current medications for the trial?
The trial protocol does not specify if you need to stop taking your current medications. However, you must be able to stop anticoagulation or anti-platelet therapy around the time of the procedure.
What data supports the effectiveness of the treatment Padeliporfin VTP for lung cancer?
Padeliporfin VTP has shown promise in treating localized prostate cancer and upper tract urothelial carcinoma by targeting blood vessels in tumors, which suggests it might be effective for other cancers like lung cancer. This treatment uses a special light-activated drug to destroy cancer cells, and its success in other cancers provides hope for its potential use in lung cancer.
12345Is Padeliporfin VTP safe for use in humans?
Padeliporfin VTP has been evaluated for safety in clinical trials for localized prostate cancer and upper tract urothelial carcinoma, showing it to be a minimally invasive treatment with a focus on safety and quality of life. While specific safety data for lung cancer is not available, its use in other conditions suggests it is generally safe in humans.
12456What makes the drug Padeliporfin VTP unique for treating lung cancer?
Padeliporfin VTP is unique because it uses a light-activated process called photodynamic therapy, which targets cancer cells with a special drug that becomes active when exposed to light, causing the cancer cells to die. This approach is different from traditional treatments like chemotherapy, which affect both cancerous and healthy cells.
7891011Eligibility Criteria
This trial is for adults with early-stage peripheral lung cancer, who are high-risk surgical candidates. Eligible patients must have a tumor ≤3cm based on CT scans and confirmed malignancy via biopsy. The tumor should be accessible by robotic bronchoscopy, not too close to the central airways or pleura, and without nodal involvement of cancer.Inclusion Criteria
I am 18 years old or older.
I am at high risk for lung cancer due to a primary lung lesion.
My cancer was confirmed malignant with a biopsy during surgery.
+7 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Treatment
Robotic assisted bronchoscopic Padeliporfin VTP lung ablation with light dose escalation to determine MTD/RP2D
1 day
1 visit (in-person)
Surgery
Surgery performed 5-21 days following the VTP procedure to assess feasibility and safety
5-21 days
Follow-up
Participants are monitored for safety and effectiveness after treatment, including evaluation of treatment-related adverse events
30 days
Participant Groups
The study tests Padeliporfin Vascular Targeted Photodynamic (VTP) therapy using robotic-assisted bronchoscopy in patients with peripheral lung tumors. It's a Phase 1/1b trial focusing on safety and optimal light dose before surgery scheduled within 5-21 days post-VTP.
2Treatment groups
Experimental Treatment
Group I: Part BExperimental Treatment1 Intervention
will be a dose expansion part at MTD/RP2D dose level identified in Part A to further assess the safety, tolerability, and treatment effect of the MTD and/ or RP2D
Group II: Part AExperimental Treatment1 Intervention
will be a monotherapy light dose escalation with single dose of Padeliporfin at light laser doses of 150, 250 and 400 mW/cm for 20 minutes.
Part A will proceed with light dose escalation and will continue until the maximum tolerated light dose (MTD) and/or recommended phase 2 dose (RP2D) is defined.
Padeliporfin VTP is already approved in European Union for the following indications:
🇪🇺 Approved in European Union as Tookad for:
- Low-risk prostate cancer
- Upper tract urothelial carcinoma (UTUC)
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Johns Hopkins University School of MedicineBaltimore, MD
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Who Is Running the Clinical Trial?
Impact Biotech LtdLead Sponsor
Steba Biotech S.A.Lead Sponsor
Impact biotech Ltd.Collaborator
References
Vascular targeted photochemotherapy using padoporfin and padeliporfin as a method of the focal treatment of localised prostate cancer - clinician's insight. [2020]Vascular targeted photochemotherapy (VTP) holds promise as a novel strategy of the focal treatment of localised prostate cancer (LPCa). It is convenient to perform, minimally invasive and can be conduct in ambulatory conditions. In this review, methodologic aspects of padoporfin- and padeliporfin-mediated VTP and its clinical application in focal treatment of LPCa as well as future perspective of this method were presented. Physicochemical and pharmacokinetic parameters of padoporphin and padeliporfin using as VTP photosensitizers were described, as well as methodologic question of radiation delivery and dosimetry, and oxygen monitoring in cancer tissue in context of VTP safety and efficiency of LPCa focal therapy were discussed. The results of clinical trials concerning application of padoporfin- and padeliporfin-mediated VTP in LPCa were also presented. The future of VTP is development of protocols, founded on the real-time feedback and rules-based approach to make this strategy a standard procedure in LPCa treatment. To evaluate clinical potential of this procedure, a cost-effectiveness analysis is also necessary.
Final Results of a Phase I Trial of WST-11 (TOOKAD Soluble) Vascular-targeted Photodynamic Therapy for Upper Tract Urothelial Carcinoma. [2023]Vascular-targeted photodynamic therapy with the intravascular photosensitizing agent padeliporfin (WST-11/TOOKAD-Soluble) has demonstrated therapeutic efficacy as an ablative treatment for localized cancer with potential adaptation for endoscopic management of upper tract urothelial carcinoma. This Phase I trial (NCT03617003) evaluated the safety of vascular-targeted photodynamic therapy with WST-11 in upper tract urothelial carcinoma.
Developments in Vascular-Targeted Photodynamic Therapy for Urologic Malignancies. [2021]With improved understanding of cancer biology and technical advancements in non-invasive management of urological malignancies, there is renewed interest in photodynamic therapy (PDT) as a means of focal cancer treatment. The application of PDT has also broadened as a result of development of better-tolerated and more effective photosensitizers. Vascular-targeted PDT (VTP) using padeliporfin, which is a water-soluble chlorophyll derivative, allows for tumor-specific cytotoxicity and has demonstrated efficacy in the management of urologic malignancies. Herein, we describe the evolution of photodynamic therapy in urologic oncology and the role of VTP in emerging treatment paradigms.
TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy: determination of optimal treatment conditions and assessment of effects in patients with localised prostate cancer. [2014]To evaluate the optimal treatment conditions and effects of TOOKAD(®) Soluble vascular-targeted photodynamic (VTP) therapy in patients with localised prostate cancer. To evaluate the safety and quality of life after TOOKAD(®) Soluble VTP treatment in patients with localised prostate cancer.
The Role of Photoactivated and Non-Photoactivated Verteporfin on Tumor. [2020]Verteporfin (VP) has long been clinically used to treat age-related macular degeneration (AMD) through photodynamic therapy (PDT). Recent studies have reported a significant anti-tumor effect of VP as well. Yes-associated protein (YAP) is a pro-tumorigenic factor that is aberrantly expressed in various cancers and is a central effector of the Hippo signaling pathway that regulates organ size and tumorigenesis. VP can inhibit YAP without photoactivation, along with suppressing autophagy, and downregulating germinal center kinase-like kinase (GLK) and STE20/SPS1-related proline/alanine-rich kinase (SPAK). In addition, VP can induce mitochondrial damage and increase the production of reactive oxygen species (ROS) upon photoactivation, and is an effective photosensitizer (PS) in anti-tumor PDT. We have reviewed the direct and adjuvant therapeutic action of VP as a PS, and its YAP/TEA domain (TEAD)-dependent and independent pharmacological effects in the absence of light activation against cancer cells and solid tumors. Based on the present evidence, VP may be repositioned as a promising anti-cancer chemotherapeutic and adjuvant drug.
Photophysical Characterization and in Vitro Phototoxicity Evaluation of 5,10,15,20-Tetra(quinolin-2-yl)porphyrin as a Potential Sensitizer for Photodynamic Therapy. [2020]Photodynamic therapy (PDT) is a selective and minimally invasive therapeutic approach, involving the combination of a light-sensitive compound, called a photosensitizer (PS), visible light and molecular oxygen. The interaction of these per se harmless agents results in the production of reactive species. This triggers a series of cellular events that culminate in the selective destruction of cancer cells, inside which the photosensitizer preferentially accumulates. The search for ideal PDT photosensitizers has been a very active field of research, with a special focus on porphyrins and porphyrin-related macrocycle molecules. The present study describes the photophysical characterization and in vitro phototoxicity evaluation of 5,10,15,20-tetra(quinolin-2-yl)porphyrin (2-TQP) as a potential PDT photosensitizer. Molar absorption coefficients were determined from the corresponding absorption spectrum, the fluorescence quantum yield was calculated using 5,10,15,20-tetraphenylporphyrin (TPP) as a standard and the quantum yield of singlet oxygen generation was determined by direct phosphorescence measurements. Toxicity evaluations (in the presence and absence of irradiation) were performed against HT29 colorectal adenocarcinoma cancer cells. The results from this preliminary study show that the hydrophobic 2-TQP fulfills several critical requirements for a good PDT photosensitizer, namely a high quantum yield of singlet oxygen generation (Φ∆ 0.62), absence of dark toxicity and significant in vitro phototoxicity for concentrations in the micromolar range.
Pharmacokinetic and tumour-photosensitizing properties of the cationic porphyrin meso-tetra(4N-methylpyridyl)porphine. [2019]The pharmacokinetic behaviour and the photodynamic properties of the cationic porphyrin meso-tetra(4N-methylpyridyl)porphine (T4MPyP 2.1 mg/kg) were examined in Balb/c mice bearing an MS-2 fibrosarcoma. The porphyrin shows good tumour localizing properties; 24 h after drug administration the tumour concentration of T4MPyP was approximately 1.2 ng/mg, while the concentrations in normal tissues were substantially lower, except for liver and spleen. In the serum, T4MPyP is preferentially transported by albumin and globulins (80.5%), while minor amounts are associated to lipoproteins (19.5%). The phototherapeutic efficiency of T4MPyP was tested by following the growth curves of fibrosarcoma irradiated by 600-680 nm (450 J/cm2) 24 h after the i.v. injection of T4MPyP (2.1 mg/kg). PDT-treated tumours showed a temporary delay in their growth compared with control tumours. The excellent selectivity of T4MPyP and its antitumour activity on photoexcitation encourage further studies for assessing the usefulness of this porphyrin in photodynamic therapy.
Combined chemotherapeutic and photodynamic treatment on human bladder cells by hematoporphyrin-platinum(II) conjugates. [2019]Four porphyrin-platinum complexes, conceived as a new approach in cancer therapy by combining the cytostatic activity of cisplatin or oxaliplatin and the photodynamic effect of hematoporphyrin in the same molecule, were studied in detail with respect to solubility and stability in cell culture medium as well as in terms of cytotoxicity and phototoxicity against J82 bladder cancer cells and UROtsa, normal urothelial cells. This study demonstrated that the most active and promising compound among the porphyrin-platinum conjugates investigated was the water-soluble porphyrin-platinum complex 4 (diammine[7,12-bis[1-(polyethyleneglycol-750-monomethylether-1-yl)ethyl]-3,8,13,17-tetramethylporphyrin-2,18-dipropionato]platinum(II)) which exhibited a synergistic antiproliferative effect compared to cisplatin and hematoporphyrin alone or a combination of the drugs.
Lipophilic cationic porphyrins as photodynamic sensitisers-Synthesis and structure-activity relationships. [2014]A convenient synthesis of a range of phosphorous and nitrogen centred lipophilic cationic porphyrins is described. In vitro assays for photodynamic activity against human colorectal adenocarcinoma cells (HT-29) reveal significant differences based on substituents around the cation centres.
Photosensitizing properties of palladium-tetraphenylporphycene on cultured tumour cells. [2006]In this study we describe photokilling properties and effects on the mitotic index (MI) of cultured HeLa cells induced by palladium(II)-tetraphenylporphycene (PdTPP(0)). The drug was synthesized by refluxing tetraphenylporphycene (TPP(0)) and PdCl2 in dimethylformamide, followed by evaporation and purification by chromatography. Cells were treated with different concentrations of PdTPPo incorporated into dipalmitoylphosphatidylcholine liposomes, and red light irradiation (lambda > 600 nm) was performed at 21 mW/cm2. No dark toxicity was found when the drug was applied under our experimental conditions. Using lethal (LD(100)) treatments, cells showed the immediate occurrence of bubbles on the plasma membrane, whereas homogeneous nuclear condensation and loss of cytoplasm appeared 3-24 h later. An increased MI was found 6-8 h after sublethal LD(25) and LD(40) treatments as well as a high proportion of abnormal metaphases with altered spindle microtubules. Chromatin condensation and fragmentation were observed 8 h after LD(75) treatments. These results show that in comparison with TPP(0), the new sensitizer PdTPPo has more efficient photokilling properties which could be very valuable for the photodynamic therapy of cancer.
Necrotic cell death induced by photodynamic treatment of human lung adenocarcinoma A-549 cells with palladium(II)-tetraphenylporphycene. [2019]In this study we describe photodamaging and photokilling effects of palladium(II)-tetraphenylporphycene (PdTPPo) (previously incorporated into dipalmitoylphosphatidylcholine liposomes) on the human lung adenocarcinoma A-549 cell line. No dark cytotoxicity was found when the drug was applied at 10(-6) M or 5 x 10(-7) M for 1 or 18 h, respectively. After 1-h treatment with 10(-7) M or 5 x 10(-7) M PdTPPo followed by red light irradiation for variable times, dose-dependent lethal effects were observed in A-549 cells. Apoptosis was not found after the above photodynamic treatments or under even milder sublethal conditions. In contrast to HeLa cells subjected to PdTPPo photosensitization where either apoptosis or necrosis were induced, morphological analysis and electrophoretical DNA pattern of A-549 cells always revealed a clearly necrotic death mechanism. However, A-549 cells died by apoptosis after serum and L-glutamine deprivation, indicating that only the photodynamically induced apoptosis was inhibited. Immunofluorescent labeling revealed that microtubules and actin microfilaments were immediately and strongly damaged by photodynamic treatments with PdTPPo. No metaphase arrest and/or mitotic alterations were observed after phototreatments. Present results show that the cell type plays a fundamental role in relation to the apoptotic or necrotic response to photosensitization, and that cytoskeletal components are important targets implicated in cell death processes.