Studies on the choice of subjects in clinical phase I tests. With emphasison evaluation of tranaminase levels prior to testing. 2.

Background: CD-13 targeted tissue factor tTF-NGR is a fusion protein selectively inducing occlusion of tumor vasculature with resulting tumor infarction. Mechanistic and pharmacodynamic studies have shown broad anti-tumor therapeutic effects in xenograft models. Methods: After successful Good Manufacturing Practice (GMP) production and before translation into clinical phase I, ICH S9 (S6) guideline-conforming animal safety, toxicology, and pharmacokinetic (PK) studies were requested by the federal drug authority in accordance with European and US regulations. Results: These studies were performed in mice, rats, guinea pigs, and beagle dogs. Results of the recently completed clinical phase I trial in end-stage cancer patients showed only limited predictive value of these non-clinical studies for patient tolerability and safety in phase I. Conclusions: Although this experience cannot be generalized, alternative pathways with seamless clinical phase 0 microdosing—phase I dose escalation studies are endorsed for anticancer drug development and translation into the clinic.

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DAVANAT®(GM-CT-01) and Colon Cancer: Preclinical and Clinical (Phase I and II) Studies

ACS Symposium Series - Glycobiology and Drug Design ◽

10.1021/bk-2012-1102.ch004 ◽

2012 ◽

pp. 89-130 ◽

Cited By ~ 7

Author(s):

Anatole Klyosov ◽

Eliezer Zomer ◽

David Platt

Keyword(s):

Colon Cancer ◽

Phase I ◽

Clinical Phase ◽

Phase I And Ii

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Toxicology Program to Support Initiation of a Clinical Phase I Program for a New Medicine

Early Drug Development ◽

10.1002/9780470613191.ch7 ◽

2010 ◽

pp. 281-307

Author(s):

Hugh E. Black ◽

Stephen B. Montgomery ◽

Ronald W. Moch

Keyword(s):

Phase I ◽

Clinical Phase

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Abstract A221: Results of preclinical and clinical phase I/II open‐label dose‐ranging trial with HE3235, a synthetic adrenal hormone, in castrate‐resistant prostate cancer

10.1158/1535-7163.targ-09-a221 ◽

2009 ◽

Cited By ~ 2

Author(s):

Bruce Montgomery ◽

Michael Morris ◽

Charles Ryan ◽

Eva Corey ◽

Dwight Stickney ◽

...

Keyword(s):

Prostate Cancer ◽

Phase I ◽

Open Label ◽

Clinical Phase ◽

Adrenal Hormone ◽

Label Dose ◽

Castrate Resistant Prostate Cancer ◽

Dose Ranging ◽

Castrate Resistant

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OptimalTTF-1: Enhancing tumor treating fields therapy with skull remodeling surgery. A clinical phase I trial in adult recurrent glioblastoma

Neuro-Oncology Advances ◽

10.1093/noajnl/vdaa121 ◽

2020 ◽

Vol 2 (1) ◽

Author(s):

Anders Rosendal Korshoej ◽

Slavka Lukacova ◽

Yasmin Lassen-Ramshad ◽

Christian Rahbek ◽

Kåre Eg Severinsen ◽

...

Keyword(s):

Phase I ◽

Compliance Rate ◽

Progression Free Survival ◽

Recurrent Glioblastoma ◽

Oncological Treatment ◽

Clinical Phase ◽

Tumor Treating Fields ◽

Skull Defects ◽

Secondary Endpoints ◽

First Recurrence

Abstract Background Preclinical studies suggest that skull remodeling surgery (SR-surgery) increases the dose of tumor treating fields (TTFields) in glioblastoma (GBM) and prevents wasteful current shunting through the skin. SR-surgery introduces minor skull defects to focus the cancer-inhibiting currents toward the tumor and increase the treatment dose. This study aimed to test the safety and feasibility of this concept in a phase I setting. Methods Fifteen adult patients with the first recurrence of GBM were treated with personalized SR-surgery, TTFields, and physician’s choice oncological therapy. The primary endpoint was toxicity and secondary endpoints included standard efficacy outcomes. Results SR-surgery resulted in a mean skull defect area of 10.6 cm2 producing a median TTFields enhancement of 32% (range 25–59%). The median TTFields treatment duration was 6.8 months and the median compliance rate 90%. Patients received either bevacizumab, bevacizumab/irinotecan, or temozolomide rechallenge. We observed 71 adverse events (AEs) of grades 1 (52%), 2 (35%), and 3 (13%). There were no grade 4 or 5 AEs or intervention-related serious AEs. Six patients experienced minor TTFields-induced skin rash. The median progression-free survival (PFS) was 4.6 months and the PFS rate at 6 months was 36%. The median overall survival (OS) was 15.5 months and the OS rate at 12 months was 55%. Conclusions TTFields therapy combined with SR-surgery and medical oncological treatment is safe and nontoxic and holds the potential to improve the outcome for GBM patients through focal dose enhancement in the tumor.

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Clinical research on new drugs (Phase I). Profile of scientific publications: data from the pre-clinical phase and bioethical aspects

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502008000600010 ◽

2008 ◽

Vol 23 (6) ◽

pp. 531-535 ◽

Cited By ~ 1

Author(s):

Vanessa de Souza Brick ◽

William Saad Hossne ◽

Rogério Saad Hossne

Keyword(s):

Data Collection ◽

Phase I ◽

New Drugs ◽

Human Beings ◽

Scientific Publications ◽

Future Studies ◽

Clinical Phase ◽

Sample Characteristics ◽

Phase Data ◽

Phase Phase

PURPOSE: To trace a profile of scientific publications, phase I, in order to know whether or not they show pre-clinical phase data, emphasizing bioethical aspects. METHODS: Sixty-one scientific articles, published in 2007, involving research in human beings using new drugs, medicines and vaccines during phase I were analysed. A schedule for data collection was elaborated in which it would be possible to analyse and evaluate those articles. The schedule included items related to the pre-clinical phase associated to the clinical phase, and items related to the sample characteristics. RESULTS: Most of research works were carried out in USA. Taking into consideration that a large number of works have been dedicated to oncologic affections, most of them were carried out in voluntary ill individuals. Information on the pre-clinical phase, phase I, was very poor or absent. Even though some authors consider the phase I research as a promising one and also suggest some future studies on phase II, the reader is not able to consider the same way, as long as there is a shortage of information on the pre-clinical phase. CONCLUSION: The profile of scientific publications showed that data deserve some reflections and analysis to better evaluate the publications on phase I.

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