Safety of Silk-elastin Sponges in Patients with Chronic Skin Ulcers: A Phase I/II, Single-center, Open-label, Single-arm Clinical Trial

Abstract H3 K27M-mutant gliomas often manifest as midline gliomas, have a dismal prognosis, and have no effective treatments. ONC201 efficacy has been shown in high-grade glioma preclinical models and durable responses with single agent ONC201 have been reported in adults with recurrent H3 K27M-mutant gliomas. These observations led to a Phase I pediatric clinical trial of ONC201 dosed by body weight. This multi-center, open-label, 3 + 3 dose-escalation and dose-expansion clinical trial (NCT03416530) for H3 K27M-mutant glioma or non-biopsied DIPG has 6 arms: arms A and E determine the RP2D in pediatric post-radiation (recurrent or not-recurrent) H3 K27M-mutant glioma patients with ONC201 administered as an oral capsule as well as a liquid formulation, respectively. Both arms have completed accrual. The study is currently enrolling newly diagnosed DIPG patients to determine the RP2D for ONC201 in combination with radiation (arm B). Dedicated assessment of intratumoral ONC201 concentrations in midline gliomas patients (arm C) and the effects of ONC201 in H3K27M DNA levels in circulating CSF (arm D) are currently enrolling patients. ONC201 as a single agent in patients with progressive H3K27M mutant tumors following irradiation (excluding DIPG/spinal cord tumors) was recently opened (arm F). Once the RP2D is confirmed, there is a dose-expansion cohort to confirm the safety, radiographic efficacy and survival with ONC201. The primary endpoints of arms A, B, and E have been established with the RP2D of 625mg scaled by body weight as a capsule or liquid formulation administered alone or in combination with radiation without incidence of dose-limiting toxicity.

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Melatonin reduces the mortality of severely-infected COVID-19 patients

Melatonin Research ◽

10.32794/mr112500115 ◽

2021 ◽

Vol 4 (4) ◽

pp. 613-616

Author(s):

Dun-Xian Tan ◽

Russel J Reiter

Keyword(s):

Clinical Trial ◽

Clinical Trials ◽

Mortality Rate ◽

Randomized Clinical Trial ◽

Control Group ◽

Mortality Reduction ◽

Single Center ◽

Open Label ◽

Melatonin Treatment ◽

The World

SARS-CoV-2 has ravaged the population of the world for two years. Scientists have not yet identified an effective therapy to reduce the mortality of severe COVID-19 patients. In a single-center, open-label, randomized clinical trial, it was observed that melatonin treatment lowered the mortality rate by 93% in severely-infected COVID-19 patients compared with the control group (see below). This is seemingly the first report to show such a huge mortality reduction in severe COVID-19 infected individuals with a simple treatment. If this observation is confirmed by more rigorous clinical trials, melatonin could become an important weapon to combat this pandemic.

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30. Open-label Phase I/II clinical trial of pyrimethamine for the treatment of chronic GM2 gangliosidosis

Molecular Genetics and Metabolism ◽

10.1016/j.ymgme.2009.10.047 ◽

2010 ◽

Vol 99 (2) ◽

pp. S14 ◽

Cited By ~ 1

Author(s):

Joe Clarke ◽

Edwin Kolodny ◽

Don Mahuran ◽

Maria Fuller ◽

Michael Tropak ◽

...

Keyword(s):

Clinical Trial ◽

Phase I ◽

Gm2 Gangliosidosis ◽

Open Label ◽

Open Label Phase

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Safety and Efficacy of Bis-Glyceryl Ascorbate (Amitose DGA) to Prevent Hand-Foot Skin Reaction in Patients With Renal Cell Carcinoma Receiving Sunitinib Therapy: Protocol for a Phase I/II, Uncontrolled, Single-Arm, Open-Label Trial (Preprint)

10.2196/preprints.14636 ◽

2019 ◽

Author(s):

Kazuhiro Yamamoto ◽

Takeshi Ioroi ◽

Kenichi Harada ◽

Satoshi Nishiyama ◽

Chikako Nishigori ◽

...

Keyword(s):

Renal Cell Carcinoma ◽

Ascorbic Acid ◽

Phase I ◽

Cell Carcinoma ◽

Skin Reaction ◽

Renal Cell ◽

Single Center ◽

Open Label ◽

Open Label Trial ◽

Hand Foot Skin Reaction

BACKGROUND Hand-foot skin reaction (HFSR) is a serious side effect induced by multiple-tyrosine kinase inhibitors (TKIs). HFSR can cause treatment interruption or decreased dosing. HFSR also markedly decreases quality of life and is associated with the therapeutic efficacy of multiple-TKIs. Therefore, the management and prevention of HFSR is an important issue; however, an effective method for its prevention has not been established. Specific ascorbic acid derivatives can reverse multiple-TKI-induced keratinocyte growth and pathological changes in vitro. OBJECTIVE This study was designed to evaluate the safety of bis-glyceryl ascorbate (Amitose DGA), a novel, hydrosoluble, and moisturizing ascorbic acid derivative, in patients with renal cell carcinoma (RCC) receiving sunitinib therapy. This study was also designed to evaluate Amitose DGA’s preventive efficacy for sunitinib-induced HFSR. METHODS This is a Phase I/II, single-center, uncontrolled, single-arm, open-label trial. We will recruit a total of 30 patients with RCC receiving sunitinib therapy, with a 2-week-on and 1-week-off schedule. The participants will apply Amitose DGA-containing cream over both palmar and plantar surfaces within two treatment cycles (ie, 6 weeks) of sunitinib in combination with a general moisturizing agent, in addition to standard-of-care processes. Safety assessments will include dermatological abnormalities, clinical laboratory tests, and incidence of adverse events. Efficacy assessments will include development of HFSR and therapeutic outcomes associated with sunitinib. RESULTS Recruitment to the study began in August 2017 and is ongoing in Japan. To date, 21 subjects have been recruited. Study completion is expected in 2021. CONCLUSIONS This is the first clinical study of Amitose DGA-containing cream in patients with RCC who are receiving sunitinib therapy. The single-center, single-arm, open-label design was selected to maximize subject exposure and increase the likelihood of achieving our study endpoints. The results will provide valuable and preliminary evidence of the effects of Amitose DGA-containing cream on HFSR. CLINICALTRIAL UMIN Clinical Trials Registry UMIN000027209; https://upload.umin.ac.jp/cgi-open-bin/ctr /ctr_view.cgi?recptno=R000031174 INTERNATIONAL REGISTERED REPOR DERR1-10.2196/14636

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Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: An open-label, single-center, single-arm clinical study.

Journal of Clinical Oncology ◽

10.1200/jco.2021.39.15_suppl.e16117 ◽

2021 ◽

Vol 39 (15_suppl) ◽

pp. e16117-e16117

Author(s):

Jian-Xu Li ◽

Ting-Shi Su ◽

Xiao-Feng Lin ◽

Yi-Tian Chen ◽

Shi-Xiong Liang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Clinical Trial ◽

Radiation Therapy ◽

Clinical Study ◽

Cancer Staging ◽

Advanced Hepatocellular Carcinoma ◽

Single Center ◽

Open Label ◽

Grade 3 ◽

Clinical Trial Information

e16117 Combining radiation therapy with anti-PD-1 for patients with advanced hepatocellular carcinoma: an open-label, single-center, single-arm clinical study Jian-Xu Li, Ting-Shi Su, Xiao-Feng Lin, Yi-Tian Chen, Shi-Xiong Liang, Bang-De Xiang; Guangxi Medical University Cancer Hospital, Nanning, China Abstract Research Funding: Jiangsu Hengrui Pharmaceuticals Co., Ltd., Shanghai, China. Guangxi Medical and Health Appropriate Technology Development and Application Project (No. S2019039), Guangxi, China. Background: Based on the results of recent studies, the PD-1 monoclonal antibodies have been approved to treat the patients with advanced hepatocellular carcinoma (HCC) by the FDA. Radiation therapy (RT) can enhance responsiveness to PD-1 monoclonal antibody by potential mechanisms. A phase Ⅱa study was conducted to assess the safety and the efficacy of combining RT with anti-PD-1 for patients with advanced hepatocellular carcinoma. Methods: Patients with advanced HCC were eligible. Stereotactic body radiation therapy (SBRT) were adopted, and the dose of radiation were Dt-PGTV 30-50 Gy/10fractions. Camrelizumab (200mg) were given intravenously every 3 weeks since the first day of RT until disease progression, or intolerable toxicity. Adverse events (AEs) and objective response rate (ORR) were summarized to assess the safety and efficacy. Results: From April 2020 to November 2020, 17 patients were enrolled (median age 54, range 32-69). 15 (88%) patients were male. 14 (82%) had ECOG performance score of 0. All the patients had Child-Pugh score A. 16 patients staged as Barcelona Clinic Liver Cancer staging C or China Liver Cancer staging Ⅲ. Extrahepatic metastases were identified in 11 (65%) patients. 13 (77%) patients were Hepatitis B virus infected. 15 (88%) patients had previously 2 lines or more chemotherapy. 9 (53%) patients had Alpha-fetoprotein level≥400 ng/ml. The ORR was 47%. The best response assessed by RECIST 1.1 was partial response (8 patients). Four patients had grade 3 immune-related adverse events (irAEs), including increased aspartate aminotransferase and alanine transaminase (n =1)，decreased hemoglobin (n =1)，decreased platelet count (n =1)，decreased neutrophil count (n =1). All grade 3 irAEs were mitigated with proper treatment. None treatment-related deaths occurred. Conclusions: In this study, RT combined with anti-PD-1 had an acceptable safety profile and indicated an effective treatment option in patients with unresectable HCC. Clinical trial information: NCT04193696. Clinical trial information: NCT04193696.

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The anti-CD6 antibody itolizumab provides clinical benefit without lymphopenia in rheumatoid arthritis patients: results from a 6-month, open-label Phase I clinical trial

Clinical & Experimental Immunology ◽

10.1111/cei.13061 ◽

2017 ◽

Vol 191 (2) ◽

pp. 229-239 ◽

Cited By ~ 8

Author(s):

P. C. Rodríguez ◽

D. M. Prada ◽

E. Moreno ◽

L. E. Aira ◽

C. Molinero ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Clinical Trial ◽

Phase I ◽

Clinical Benefit ◽

Phase I Clinical Trial ◽

Open Label ◽

Open Label Phase

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A phase I/II study combining tosedostat with capecitabine in patients with metastatic pancreatic adenocarcinoma.

Journal of Clinical Oncology ◽

10.1200/jco.2016.34.4_suppl.tps471 ◽

2016 ◽

Vol 34 (4_suppl) ◽

pp. TPS471-TPS471

Author(s):

Andrea S. Teague ◽

Manik A. Amin ◽

Kian-Huat Lim ◽

Albert C. Lockhart ◽

Ashiq Masood ◽

...

Keyword(s):

Clinical Trial ◽

Amino Acids ◽

Phase I ◽

Phase Ii ◽

Primary Objective ◽

Cellular Stress Response ◽

Ductal Adenocarcinoma ◽

Open Label ◽

Pancreatic Cancer Cells ◽

Dismal Prognosis

TPS471 Background: Metastatic pancreatic ductal adenocarcinoma (PDAC) has a dismal prognosis. Recent advances with fluorouracil in combination with oxaliplatin and irinotecan (FOLFIRINOX) and nab-paclitaxel combined with gemcitabine (AG) have improved survival in patients with PDAC. A fluorouracil-based regimen is recommended for patients who progress after a gemcitabine-based regimen. Tosedostat is an oral aminopeptidase inhibitor shown to have anti-proliferative effects in malignancies. Aminopeptidase inhibitors disrupt the cleavage of amino acids from peptides downstream of proteasomal degradation, preventing the recycling of amino acids needed for new protein synthesis. This leads to intracellular depletion of amino acids, resulting in a cellular stress response known as the amino acid deprivation response, which leads to apoptosis. Because pancreatic cancer cells frequently upregulate expression of these aminopeptidases, aminopeptidases inhibitors hold therapeutic promise. Methods: This is a single institution phase I/II open-label trial to evaluate the safety and tolerability of tosedostat plus capecitabine in patients with metastatic PDAC that have progressed after a gemcitabine-based regimen. The phase I part will be conducted in a dose de-escalation fashion, with two planned dose levels of tosedostat (120mg or 60mg) p.o. daily on days 1 to 21 with capecitabine 1000 mg/m2 p.o. BID on days 1 to 14 of a 21-day cycle. If more than one patient in the tosedostat (120 mg) cohort experiences a dose limiting toxicity (DLT), then 6 more patient will be enrolled to the tosedostat (60 mg) cohort. A total of 36 patients will be enrolled in the phase II portion. Primary objective of the phase I portion is to determine the maximum tolerated dose and DLTs of tosedostat and capecitabine combination therapy. Primary objective of the phase II portion is to determine the progression-free survival at 3 months. Secondary objectives are to determine the overall response rate, time-to-progression, overall survival and CA 19-9 response. Exploratory objectives are to explore the predictive molecular biomarkers for treatment response and to explore the prognostic biomarkers. Clinical trial: NCT02352831. Clinical trial information: NCT02352831.

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