Multi-Institutional Phase I Trials of Anticancer Agents

Dowlati, Afshin; Manda, Sudhir; Gibbons, Joseph; Remick, Scot C.; Patrick, Lauren; Fu, Pingfu

doi:10.1200/jco.2007.13.3793

Cited by 26 publications

(15 citation statements)

References 4 publications

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“…Only few and old studies address the issue of the crucial animal-man transfer [16,17]. As previously reported [18], the present analysis suggests that the number of study centers do not significantly modify the accrual period. The concept of increasing the number of study centers to speed up accrual remains purely theoretical.…”

Section: Discussionsupporting

confidence: 60%

Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trials

et al. 2009

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Section: Discussionsupporting

confidence: 60%

Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trials

et al. 2009

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“…The involvement of more than three study sites, however, should be discouraged, since each investigator may only manage a limited number of patients, which dilutes valuable individual experience. 11 Thus, multiple factors need to be considered when determining the number of required study sites. The feasibility process should include a discussion concerning the balance of timelines and quality.…”

mentioning

confidence: 99%

First-in-human Phase 1 Studies in Oncology: The New Challenge for Investigative Sites

Salzberg¹

2012

RMMJ

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Abbreviations: FIH, first-in-human; IRRs, infusion-related reactions; MTD, maximum tolerated dose; PhRMA, Pharmaceutical Research and Manufacturers of America; RP2D, recommended phase 2 dose. Citation ABSTRACTPhase 1 first-in-human studies with anti-cancer products differ from other phase 1 studies in that they are evaluated in patients rather than healthy volunteers. The rationale design of targeted drugs triggers changes in the design of these studies. Patient populations are more precisely defined and pose a challenge to the efficient inclusion of study patients. Objectives shift from the definition of a maximum tolerated dose to the evaluation of a recommended phase 2 dose. Other challenges related to the efficacy and safety profile of novel targeted anti-cancer drugs call for changes in designing first-in-human studies, such as definitions of biological doses, collection of fresh tumor tissue for surrogate marker analyses, and the management of infusion-related reactions with monoclonal antibodies.Consequently, the conduct of phase 1 clinical trials in oncology requires changes. Corresponding education with particular focus on phase 1 trials and on the complex drug development process needs to be an integrated part of the medical oncology curriculum for physicians and nursing staff. This is a crucial element for institutions to remain or become clinical research sites for phase 1 studies, and to participate in the drug development process of novel anti-cancer compounds in the future.

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“…The “other” category incorporated sarcomas, melanomas, gynecological malignancies and other less common tumors such as carcinoid. This database shows that 59% of published phase I trials during this period were sponsored by the pharmaceutical industry [2]. …”

Section: Methodsmentioning

confidence: 99%

Temporal evolution of patient characteristics enrolled on phase I trials

et al. 2009

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Summary Purpose Phase I trials serve a crucial role in anticancer drug development. Given the explosion in the number of both approved anticancer therapies and agents in development, we hypothesized that the characteristics of patients enrolling on phase I clinical trials is evolving. Patients and Methods We reviewed 476 published phase I trials over the past decade encompassing 15,100 patients and determined the following characteristics for patients enrolled: age; percentage with ECOG PS of 0, 1, or 2; sex; race; and number of prior chemotherapeutic therapies received: 0, 1, 2 or ≥3. We also identified the major tumor types enrolled: colorectal, lung, renal, breast, head/neck or “other”. The change of patient characteristics over time as well as between the first half of studied period (period 1 = 1998–2001) and the second half period (period 2 = 2002– 2006) was analyzed. Results Colorectal and lung cancer patients together comprise ~35% of all patients enrolled on phase I trials and this has not changed over the past decade. The contribution of “other” malignancies has however significantly increased over time. The proportion of patients with PS2 has declined while that of PS1 has increased. The proportion of patients with ≥3 prior therapies prior to study enrollment has also significantly increased. Conclusion The shifting of patient characteristics especially as related to tumor types enrolled and number of prior therapies has important implications for future design of studies and inadequate attention to these issues may slow the accrual process.

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Multi-Institutional Phase I Trials of Anticancer Agents

Abstract: Multi-institutional phase I studies do not decrease the time to study completion and result in an increase in number of patients per trial. One third of trials with targeted agents failed to determine an MTD.

Cited by 26 publications

References 4 publications

Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trials

Justification of the starting dose as the main determinant of accrual time in dose-seeking oncology phase 1 trials

First-in-human Phase 1 Studies in Oncology: The New Challenge for Investigative Sites

Temporal evolution of patient characteristics enrolled on phase I trials

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