scholarly journals Ethical Justification of Involving Human Volunteers in Phase 1 Trials

2017 ◽  
Vol 8 (2) ◽  
pp. 19-22
Author(s):  
Zoheb Rafique
Keyword(s):  
Clinical Trials ◽  
Standard Treatment ◽  
Phase 1 ◽  
Treatment Options ◽  
Experimental Treatment ◽  
Human Beings ◽  
Ethical Justification ◽  
Phase 1 Trials ◽  
Medical Benefit ◽  
Human Volunteers

Tremendous development in recent medical science and the consequent discoveries resulting in successful prevention and also cure of different diseases are shared by clinical research involving the human volunteers. Preceding the trials in the human subjects, and to ensure safety, the proposed drug and other interventions are either tested in animals (vivo) or in laboratory (vitro) to evaluate initial safe starting dose for the human beings and to key out the benchmarks for the clinical monitoring for the potential unfavorable effects. These pre human trials might not necessarily protect against the untoward effects in the human beings as happened in the case of thalidomide tragedy, which caused disability and killed thousands of babies born to the mothers, those who took this medicine. Use of healthy human volunteers in the preliminary experiments or phase I clinical trials either reduces or excludes risks of subsequent undesirable effects in the future trails (1). Phase-1 trials are conducted in order to test the safety, reactions and immunogenicity of vaccines in volunteers. Novel treatments for the cancer are first tested in phase 1 trials enrolling the patients with advanced disease, who have exhausted the standard treatment options. Phase-1 oncology trials are the pivot point in the translation of new cancer therapies from bench to bedside. Nevertheless, these trials remain ethically controversial. The controversy stems from the fact that, classically, phase-1 oncology clinical trials involve first-in-human testing of experimental treatment candidates in patients with a terminal diagnosis, who typically have exhausted standard treatment options. Commentators on the ethics of phase-1 clinical trials make diametrically opposed claims about the prospect of direct medical benefit from participation in these trials-benefits that can be attributed to receiving the experimental treatment intervention. One camp of benefit skeptics, inhabited mainly by bioethicists, characterizes this form of research as lacking any reasonable prospect of direct medical benefit. They see an ethical cloud hovering over phase-1 trials, because the vast majority of patients volunteer for phase-1 trials out of a motivation to receive medical benefit. In the view of these skeptics, such patients therefore harbor a ‘therapeutic misconception’ about research participation. This misconception calls into question the validity of informed consent and thereby undercuts the ethical basis of these trials (2). In this paper, I will discuss the ethical justification of the participation of human volunteers in phase-1 trials.

Relapsed Multiple Myeloma

Hematology ◽  
2010 ◽  
Vol 2010 (1) ◽  
pp. 303-309 ◽  
Author(s):  
Sagar Lonial
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Phase 1 ◽  
Treatment Options ◽  
Single Agent ◽  
Great Promise ◽  
New Agents ◽  
Ongoing Work ◽  
The Many

Abstract Advances in treatment options for patients with multiple myeloma have made a significant impact on the overall survival of patients and have helped achieve levels of response and duration of remission previously not achievable with standard chemotherapy-based approaches. These improvements are due, in large part, to the development of the novel agents thalidomide, bortezomib, and lenalidomide, each of which has substantial single-agent activity. In addition, a large number of second-generation agents are also in clinical development, such that the repertoire of available treatment options continues to expand. To better interpret clinical trials performed in the relapsed setting, it is important that definitions of relapse categories are used to help better pinpoint the specific benefit for a given therapy, especially in the combination therapy setting as it aids in determining if ongoing work should be continued or abandoned for a given new agent. Insights from preclinical modeling and in vitro work have identified several new combinations, new targets and second- or third-generation versions of existing targets that hold great promise in the setting of relapsed myeloma. Combinations of thalidomide, bortezomib, and lenalidomide with conventional agents or among each other have resulted in enhanced response rates and efficacy. Clinical trials of agents such as carfilzomib, pomalidomide, vorinostat, panobinostat, and elotuzomab are just a few of the many exciting new compounds that are being tested in phase 1 and phase 2 clinical trials for relapsed patients. Further clinical and translational testing are critical to better understanding how best to combine these new agents, as well as identifying patient populations that may best benefit from treatment with these developing new agents.

scholarly journals EPCT-09. CLR 131 IN PATIENTS WITH RELAPSED OR REFRACTORY PEDIATRIC MALIGNANCIES

2020 ◽  
Vol 22 (Supplement_3) ◽  
pp. iii305-iii305
Author(s):  
Diane Puccetti ◽  
Mario Otto ◽  
Daniel Morgenstern ◽  
Kenneth DeSantes ◽  
Steven Cho ◽  
...  
Keyword(s):  
Brain Tumors ◽  
Dose Level ◽  
Standard Treatment ◽  
Phase 1 ◽  
Treatment Options ◽  
Malignant Cells ◽  
Single Infusion ◽  
Eligibility Criteria ◽  
Pediatric Malignancies ◽  
Normal Tissues

Abstract BACKGROUND CLR 131 is a novel targeted radiotherapeutic that exploits the selective uptake and retention of phospholipid ethers by malignant cells. CLR 131 selectively delivers radiation to malignant tumor cells, thus minimizing radiation exposure to normal tissues. OBJECTIVE CLR 131 is being examined in a Phase 1 trial, CLOVER-2 (NCT03478462), to determine the safety, tolerability, and initial efficacy of CLR 131 in children and adolescents with relapsed/refractory malignancies. METHODS Eligibility criteria include children with relapsed or refractory solid tumors or malignant brain tumors for which there are no standard treatment options with curative potential. Subjects must be between ages 2 and 21 with no limit to the number of prior therapies. CLR 131 is administered as a single infusion in escalating doses beginning at 15 mCi/m2. Adverse events (AEs) are graded by NCI-CTCAE v5. RESULTS As of 10Jan2020, four subjects with brain tumors have received CLR 131; one at 15 mCi/m2 and three at 30 mCi/m2. Diagnoses included DIPG (2), glioblastoma (1), and medulloblastoma (1). Median age is 13 years (range 10–15) and patients received a median of two prior therapies (range 1 to 8). There were no treatment emergent AEs at the 15 mCi/m2 dose level attributed to CLR 131 by the investigator. Assessment of the 30 mCi/m2 dose level is ongoing. CONCLUSIONS CLR 131 is a unique, first in class targeted radiotherapeutic for pediatric malignancies. Preliminary data shows an acceptable and expected safety profile in this patient population. Dose escalation to determine the highest tolerated dose is ongoing.

Survival and signals of response in advanced sarcoma patients enrolled on phase 1 trials in the era of precision oncology and novel immunotherapies.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11063-11063
Author(s):  
Shiraj Sen ◽  
Kenneth R. Hess ◽  
David S. Hong ◽  
Gerald Steven Falchook ◽  
Roberto Pestana ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Soft Tissue ◽  
Ewing’S Sarcoma ◽  
Ewing's Sarcoma ◽  
Phase 1 ◽  
Phase 1 Trials ◽  
Best Response ◽  
Bone Sarcomas ◽  
Us Fda ◽  
Advanced Sarcoma

11063 Background: Few effective US FDA approved therapies exist for refractory, metastatic sarcomas. Many of these patients therefore enroll onto phase 1 clinical trials. Because tumor-specific outcomes are not always reported in less common cancers such as sarcomas, outcomes of sarcoma patients treated with novel immunotherapy and targeted therapy approaches remains unknown. Methods: We analyzed clinical and next generation sequencing data from all sarcoma patients treated on phase 1 trials at MD Anderson Cancer Center (MDACC) and performed logistic and Cox proportional hazards regression analyses to evaluate response rate (RR), median time to progression (mTTP), clinical benefit rate (CBR; defined as CR, PR, or SD > 6 months), and median overall survival (OS). Results: Among the 406 patients with advanced sarcomas (321 soft tissue sarcoma, 85 bone sarcomas) treated on phase 1 trials at MDACC from May 2006 to May 2018, median age was 53 (range 11-84), 48% were female, with a median 3 prior lines of therapy (range 0-9). The most commonly treated soft tissue sarcoma subtypes included leiomyosarcoma (n = 66; 16%), liposarcoma (n = 52; 13%), GIST (n = 44; 11%), UPS (n = 14; 3%), and synovial sarcoma (n = 11; 3%) and most commonly treated bone sarcomas included osteosarcoma (n = 34; 8%), chondrosarcoma (n = 28; 7%), and Ewing’s sarcoma (n = 25; 6%). RR was 7% (95% CI 5, 10), mTTP was 2.9 months (95%CI 2.6, 3.1), CBR was 24% (95% CI 20, 29), mOS was 17.2 months (95% CI 13.8, 20.8). 2 patients had a CR as best response, 1 chondrosarcoma patient treated with an anti-APO2L/Trail agent and 1 Ewing’s sarcoma patient treated with the combination of an IGF1R inhibitor plus mTOR inhibitor. 26 patients (6%) had a PR as best response using novel immunotherapies targeting PD1, PDL1 plus CCR4, CTLA4 plus KIT, and TLR7/8 and novel targeted therapies against TRK, LRRC15, cMET, mTOR, VEGF, MDM2, KIT/PDGFRA, and FGFR. Responses were seen across sarcoma subtypes - ASPS, UPS, myxoid sarcoma, liposarcoma, GIST, carcinosarcoma, clear cell sarcoma, embryonal rhabdomyosarcoma, epitheliod sarcoma, fibrious histiosarcoma, and Ewing’s sarcoma. Conclusions: Our analysis identifies a reasonable survival in heavily pretreated, metastatic refractory sarcoma patients with responses seen with novel targeted therapies and immunotherapies that are not yet US-FDA approved. Biomarker analysis is ongoing to help identify the subset of responders in our cohort. Advanced sarcoma patients should be considered for molecular profiling and early phase clinical trials.

scholarly journals Non-Peutz–Jeghers syndrome-associated ovarian sex cord tumor with annular tubules treated by radiotherapy: a case report and literature review

2021 ◽  
Vol 49 (3) ◽  
pp. 030006052199656
Author(s):  
Cheng Li ◽  
Reyida Aishajiang ◽  
Yongliang Teng ◽  
Tiankai Xu ◽  
Lijuan Ding ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Case Report ◽  
Literature Review ◽  
Large Scale ◽  
Standard Treatment ◽  
Treatment Options ◽  
High Serum ◽  
Serum Estradiol ◽  
Sharp Reduction ◽  
Peutz Jeghers Syndrome

There are no standard treatment options for metastatic and recurrent non-Peutz–Jeghers syndrome (PJS)-associated sex cord tumor with annular tubules (SCTAT). The effects of chemotherapy and/or radiotherapy are still not well-defined. Herein, we present a case of a metastatic and recurrent non-PJS-associated SCTAT showing high serum estradiol and progesterone concentrations after surgery and chemotherapy. Radiotherapy (50 Gy/25 fractions) triggered a sharp reduction in the sizes of the metastatic and recurrent masses, and estradiol and progesterone concentrations. Accordingly, we consider that radiotherapy might be effective and safe for metastatic and recurrent SCTAT. The roles of radiotherapy in non-PJS SCTAT should be further validated in large-scale prospective clinical trials.

scholarly journals What do patients with unmet medical needs want? A qualitative study of patients’ views and experiences with expanded access to unapproved, investigational treatments in the Netherlands

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Eline M. Bunnik ◽  
Nikkie Aarts
Keyword(s):  
Clinical Trials ◽  
Qualitative Study ◽  
Standard Treatment ◽  
Treatment Options ◽  
Safety And Efficacy ◽  
Expanded Access ◽  
Medical Needs ◽  
Investigational Drugs ◽  
Unmet Medical Needs ◽  
Access Programs

Abstract Background Patients with unmet medical needs sometimes resort to non-standard treatment options, including the use of unapproved, investigational drugs in the context of clinical trials, compassionate use or named-patient programs. The views and experiences of patients with unmet medical needs regarding unapproved, investigational drugs have not yet been examined empirically. Methods In this qualitative study, exploratory interviews and focus groups were held with patients with chronic or life-threatening diseases (n = 39), about topics related to non-standard treatment options, such as the search for non-standard treatment options, patients’ views of the moral obligations of doctors, and the conditions under which they would or would not wish to use non-standard treatment options, including expanded access to unapproved, investigational drugs. Results Respondents had very little knowledge about and/or experience with existing opportunities for expanded access to investigational drugs, although some respondents were actively looking for non-standard treatment options. They had high expectations of their treating physicians, assuming them to be aware of non-standard treatment options, including clinical trials elsewhere and expanded access programs, and assuming that they would inform their patients about such options. Respondents carefully weighed the risks and potential benefits of pursuing expanded access, citing concerns related to the scientific evidence of the safety and efficacy of the drug, side effects, drug-drug interactions, and the maintaining of good quality of life. Respondents stressed the importance of education and assertiveness to obtain access to good-quality health care, and were willing to pay out of pocket for investigational drugs. Patients expressed concerns about equal access to new and/or non-standard treatment options. Conclusion When the end of a standard treatment trajectory comes into view, patients may prefer that treating physicians discuss non-standard treatment options with them, including opportunities for expanded access to unapproved, investigational drugs. Although our respondents had varying levels of understanding of expanded access programs, they seemed capable of making well-considered choices with regard to non-standard treatment options and had realistic expectations with regard to the safety and efficacy of such options. Dutch patients might be less likely to fall prey to false hope than often presumed.

Communication about standard treatment options and clinical trials: can we teach doctors new skills to improve patient outcomes?

2011 ◽  
Vol 21 (12) ◽  
pp. 1265-1274 ◽  
Author(s):  
Jürg Bernhard ◽  
Phyllis Butow ◽  
Julie Aldridge ◽  
Ilona Juraskova ◽  
Karin Ribi ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Patient Outcomes ◽  
Standard Treatment ◽  
Treatment Options ◽  
Improve Patient

scholarly journals Integration of new or experimental treatment options and new approaches to clinical trials

2005 ◽  
Vol 16 ◽  
pp. viii30-viii35 ◽  
Author(s):  
M. Quinn ◽  
J. Pfisterer ◽  
E. Avall-Lundqvist ◽  
M. Bookman ◽  
D. Bowtell ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Treatment Options ◽  
Experimental Treatment ◽  
New Approaches

Randomized Trial of Informed Consent and Recruitment for Clinical Trials in the Immediate Preoperative Period 

1999 ◽  
Vol 91 (4) ◽  
pp. 969-969 ◽  
Author(s):  
Paul S. Myles ◽  
Helen E. Fletcher ◽  
Sesto Cairo ◽  
Hilary Madder ◽  
Roderick McRae ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Informed Consent ◽  
Standard Treatment ◽  
Elective Surgery ◽  
Experimental Treatment ◽  
Treatment Allocation ◽  
Institutional Ethics ◽  
Significant Difference ◽  
Male Patients ◽  
English Speaking

Background The standard process of obtaining informed consent sometimes prevents physicians or patients from participating in clinical trials, partly because they are concerned about eventual treatment allocation or the physician is concerned the patient might harbor some uncertainty about the best treatment. Alternative randomization methods have been advocated that may address these and other concerns. Methods After institutional ethics committee gave its approval, the authors interviewed 770 patients before operation and asked them to consider enrolling in a mock anesthesia trial. Patients were allocated randomly to one of five methods of randomization and consent: one-sided informed consent (the most common approach), prerandomized consent to experimental treatment, prerandomized consent to standard treatment, one-sided physician-modified informed consent, or one-sided patient-modified informed consent. Recruitment rates were compared and sociodemographic and perioperative predictors of recruitment were identified. Results The randomization method did not result in any significant difference in recruitment rates: one-sided informed consent, 55.6%; prerandomized consent to experimental treatment, 53.3%; prerandomized consent to standard treatment, 53%; one-sided physician-modified informed consent, 60.7%; and one-sided patient-modified informed consent, 56.7% (P = 0.66). Multivariate predictors of recruitment were patient age >45 yr (odds ratio, 1.44; 95% confidence interval [CI], 1.08 to 1.93), English-speaking at home (1.49; 1.0 to 2.21), and male researcher-male patient interaction (1.37; 1.20 to 1.57). Conclusions No evidence emerged that alternative randomization and consent designs resulted in increased recruitment rates compared with simple one-sided informed consent for a sham anesthesia trial in patients awaiting elective surgery. Older, male patients were more likely to provide consent.

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