Risks and Benefits of Phase 1 Clinical Trial Participation

Mahipal, Amit; Nguyen, Danny

doi:10.1177/107327481402100303

Cited by 18 publications

(13 citation statements)

References 31 publications

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“…The Mayo Clinic GTB experience of a Clinical Benefit Rate of 8% (13/165) on an intent to treat basis (Tables 3 and 4) is comparable to the 6% response rate expected in phase I clinical studies [12]. Some patients received testing before exhausting standard of care (SOC) options (14/92), thus elected to continue SOC treatment before targeted therapy (Table 3).…”

Section: Resultsmentioning

confidence: 83%

Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery

et al. 2017

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BackgroundThe ability to analyze the genomics of malignancies has opened up new possibilities for off-label targeted therapy in cancers that are refractory to standard therapy. At Mayo Clinic these efforts are organized through the Center for Individualized Medicine (CIM).ResultsPrior to GTB, datasets were analyzed and integrated by a team of bioinformaticians and cancer biologists. Therapeutically actionable mutations were identified in 65% (92/141) of the patients tested with 32% (29/92) receiving genomically targeted therapy with FDA approved drugs or in an independent clinical trial with 45% (13/29) responding. Standard of care (SOC) options were continued by 15% (14/92) of patients tested before exhausting SOC options, with 71% (10/14) responding to treatment. Over 35% (34/92) of patients with actionable targets were not treated with 65% (22/34) choosing comfort measures or passing away.Materials and MethodsPatients (N = 165) were referred to the CIM Clinic between October 2012 and December 2015. All patients received clinical genomic panel testing with selected subsets receiving array comparative genomic hybridization and clinical whole exome sequencing to complement and validate panel findings. A genomic tumor board (GTB) reviewed results and, when possible, developed treatment recommendations.ConclusionsTreatment decisions driven by tumor genomic analysis can lead to significant clinical benefit in a minority of patients. The success of genomically driven therapy depends both on access to drugs and robustness of bioinformatics analysis. While novel clinical trial designs are increasing the utility of genomic testing, robust data sharing of outcomes is needed to optimize clinical benefit for all patients.

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Section: Resultsmentioning

confidence: 83%

Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery

et al. 2017

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“…Given that molecular-targeted or 323 324 325 326 327 328 329 330 331 332 333 334 335 336 337 338 339 340 341 342 343 344 345 346 347 348 349 350 351 352 353 354 355 356 357 358 359 360 361 362 363 364 365 366 367 368 369 370 371 372 373 374 375 376 377 378 379 380 381 382 383 384 385 386 387 388 389 390 391 392 393 394 395 396 397 398 399 400 401 402 403 404 405 406 407 408 409 410 411 412 413 414 415 416 417 418 419 420 421 422 423 424 425 426 427 428 429 biological agents do not exert any toxicity-related effects, therapeutic benefits, even in small dosages, as well as any unexpected adverse events of such therapies could be conceivably anticipated in FIH research. 57,58 However, early exposure to a subtherapeutic dose of an intervention with immunerelated features during a developmental phase may result in the development of antibodies in the subjects' bodies which in turn may lead to a loss of response when an optimal therapeutic dose is later proven. 59 Gene transfer and pluripotent stem cells therapies are some other novel therapies which pose an e...…”

Section: Risk-benefit Assessmentmentioning

confidence: 98%

Ethical considerations and challenges in first-in-human research

Koonrungsesomboon

Laothavorn

Karbwang

2016

Translational Research

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“…Since new molecules, often high-risk drugs, are tested for the first time on humans in phase I CTs, the ethical aspect of these studies has always been subject to discussion 5–7 ; for this reason, it has been deemed essential to take careful precautions and to comply with rigorous quality standards to protect the rights, safety, and well-being of the participants. 8…”

Section: Introductionmentioning

confidence: 99%

Phase I studies: a test bench for Italian clinical research

Cagnazzo

Nanni

Arizio

et al. 2019

Tumori

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Background: The Agenzia Italiana del Farmaco (AIFA) Determination 809/2015 sets all the requirements that clinical units and laboratories must meet in order to conduct phase I studies. Requirements include buildings, equipment, personnel, emergency management, as well as quality requirements defined in a set of standard operating procedures. Methods: In September 2018, the Italian Association of Medical Oncology working group, Clinical Research Coordinator, created an anonymous survey addressed to 51 medical directors of oncologic/hematologic clinical phase I units and all medical directors of generic and transversal units located in Italy and listed at the AIFA website. Results: Questionnaires from 24 institutions were collected, 9 previously inspected by competent authorities. All surveyed structures are certified to conduct profit studies and 1 is authorized to include healthy volunteers; 15 units implemented a Clinical Trial Quality Team in order to conduct nonprofit studies. At the time of data collection, a total of 398 proposals for phase I trials have been received, more than 50% coming from 3 institutes. A total of 144 phase I studies were active, with a median of 2.5 (Q1–Q3=0–6) studies for each center and asymmetric distribution of proposals. Conclusion: The considerable number of proposals received from the interviewed centers indicates that Italy plays an important role in the international pharmaceutical scene, despite bureaucratic procedures that threaten exclusion from decision-making. The AIFA Determination will be an important opportunity to acquire a competitive working approach.

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Risks and Benefits of Phase 1 Clinical Trial Participation

Cited by 18 publications

References 31 publications

Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery

Experience with precision genomics and tumor board, indicates frequent target identification, but barriers to delivery

Ethical considerations and challenges in first-in-human research

Phase I studies: a test bench for Italian clinical research

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