Phase I trial of cancer vaccine with multiple peptides derived from novel onco-antigen and anti-angiogenic antigens for patients with advanced non-small cell lung cancer (NSCLC).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e13015-e13015
Author(s):  
Hiroyuki Suzuki ◽  
Takeo Hasegawa ◽  
Jun Ohsugi ◽  
Mika Hoshino ◽  
Mitsunori Higuchi ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Phase I Trial ◽  
Survival Rates ◽  
Peptide Vaccine ◽  
Phase I Clinical Trials ◽  
Two Phase ◽  
Immunological Responses ◽  
Clinical Responses

e13015 Background: Two phase I clinical trials were conducted on patients with advanced or recurrent NSCLC to evaluate the safety, immunogenicity and clinical response of a multiple peptide vaccine that incorporates four epitope peptides. This vaccine is comprised of novel HLA-A24-restricted oncoantigens, including two of the following three peptides; up-regulated lung cancer 10 (URLC10), TTK protein kinase (TTK) and cell division associated 1 (CDCA1), in addition to peptides derived from vascular endothelial growth factor receptor 1 (VEGFR1) and 2 (VEGFR2). Methods: Peptides derived from URLC10, TTK, VEGFR1 and VEGFR2 were tested in Trial 1, while peptides derived from URLC10, CDCA1, VEGFR1 and VEGFR2 were tested in Trial 2. Fifteen HLA-24-positive patients with NSCLC who had not responded to standard therapy were enrolled in this classic 3 patient per dose per cohort phase I trial, designed with varying dosages (Trial 1; 0.5mg, 1mg and 3mg, Trial 2; 1mg, 3mg). Vaccines were administered weekly by subcutaneous injection into patients’ axillary region with Montanide ISA-51 incomplete Freund’s adjuvant until progressive disease occurred and/or patients refused further treatment. Immunological responses were evaluated by INF-gamma ELiSPOT assays. Results: Vaccinations were well-tolerated withno severe treatment-associated adverse events. Specific T cell responses were induced in all patients against at least one epitope peptide. However, weak immunological responses were found in the 0.5mg group compared with the 1mg and 3mg groups in Trial 1, therefore the 0.5mg group was excluded in Trial 2. In terms of clinical responses, no complete and partial responses were found, however 9 of 15 patients (60 %) were categorized with stable disease. The median overall survival time was 13.2 months, while 1- and 2-year survival rates were 52.5% and 32.8% respectively. Conclusions: Multiple peptide vaccination therapy using four novel peptides was safe, and could possibly be effective in extending the patients’ survival. These encouraging immunological and clinical responses could provide a case for further stages of clinical trials.

scholarly journals Provider Recommendations for Phase I Clinical Trials Within a Shared Decision-Making Model in Phase I Cancer Clinical Trial Discussions

2020 ◽  
Vol 16 (9) ◽  
pp. e859-e867
Author(s):  
Rachel S. Hianik ◽  
Gavin P. Campbell ◽  
Eli Abernethy ◽  
Colleen Lewis ◽  
Christina S. Wu ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Decision Making ◽  
Clinical Trials ◽  
Phase I ◽  
Shared Decision Making ◽  
Phase I Trial ◽  
Performance Status ◽  
Shared Decision ◽  
Phase I Clinical Trials ◽  
Decision Making Model

PURPOSE: Debate continues over whether explicit recommendations for a clinical trial should be included as an element of shared decision making within oncology. We aimed to determine if and how providers make explicit recommendations in the setting of phase I cancer clinical trials. METHODS: Twenty-three patient/provider conversations about phase I trials were analyzed to determine how recommendations are made and how the conversations align with a shared decision-making framework. In addition, 19 providers (9 of whose patient encounters were observed) were interviewed about the factors they consider when deciding whether to recommend a phase I trial. RESULTS: We found that providers are comprehensive in the factors they consider when recommending clinical trials. The two most frequently stated factors were performance status (89%) and patient preferences (84%). Providers made explicit recommendations in 19 conversations (83%), with 12 of those being for a phase I trial (12 [63%] of 19). They made these recommendations in a manner consistent with a shared decision-making model; 18 (95%) of the 19 conversations during which a recommendation was made included all steps, or all but 1 step, of shared decision making, as did 11 of the 12 conversations during which a phase I trial was recommended. In 7 (58%) of these later conversations, providers also emphasized the importance of the patient’s opinion. CONCLUSION: We suggest that providers not hesitate to make explicit recommendations for phase I clinical trials, because they are able to do so in a manner consistent with shared decision making. With further research, these results can be applied to other clinical trial settings.

Stereobody radiotherapy for nodal recurrences in oligometastatic patients: a pooled analysis from two phase I clinical trials

2020 ◽  
Vol 37 (4) ◽  
pp. 519-529
Author(s):  
Francesco Deodato ◽  
Milena Ferro ◽  
Savino Cilla ◽  
Anna Ianiro ◽  
Milly Buwenge ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Pooled Analysis ◽  
Phase I Clinical Trials ◽  
Two Phase

scholarly journals Informal professionalization of healthy participants in phase I clinical trials in Russia

2019 ◽  
Vol 16 (6) ◽  
pp. 563-570 ◽  
Author(s):  
Olga Zvonareva ◽  
Igor Pimenov ◽  
Natalia Kutishenko ◽  
Igor Mareev ◽  
Sergey Martsevich ◽  
...  
Keyword(s):  
Phase I ◽  
Phase I Trial ◽  
Trial Participation ◽  
Phase I Trials ◽  
Phase I Clinical Trials ◽  
Skilled Workers ◽  
Structured Interviews ◽  
Two Phase ◽  
Trial Participants ◽  
Healthy Participants

Background: Previous social science research has shown how some healthy phase I trial participants identify themselves as workers and rely on trials as a major source of income. The term “professionalization” has been used to denote this phenomenon. Purpose: We aim to examine a component of healthy trial participants’ professionalization that has not yet been systematically studied: how repeat phase I trial participants develop and claim expertise that distinguishes them from others and makes them uniquely positioned to perform high-quality clinical trial labor. We also aim to explain the significance of these research results for protection of healthy participants in phase I trials. Methods: This qualitative exploratory study was conducted in Russia, in two phase I trial units. It involved semi-structured interviews with 28 healthy trial participants with varying lengths of experience in trials, observations of work done in trial units, and interpretive conversations with investigative staff. Results: Interviewed healthy individuals who repeatedly participate in phase I trials describe developing knowledge and skills that involve appreciating the meaning of trial procedures, coming up with techniques to efficiently follow them, organizing themselves and others in the course of a trial, and sharing tacit ways of doing trial work well with other less experienced participants. Our results suggest that a prerequisite for such expertise-centered professionalization is the emergence of a positive identity linked to seeing value in trial participation work. A crucial component of professionalization thus understood is the development of a work ethic that entails caring about results and being reliable partners for investigators. Limitations: The attitudes and behaviors presented in this article are not suggested to be universally shared among healthy trial participants, but rather represent a particular instance of professionalization that coexists with other views and tactics. Conclusions: A way of better protecting healthy trial participants begins with recognizing their skills, knowledge, and the centrality of the contribution they are making to pharmaceutical research. Currently, the expertise of experienced trial participants is recognized on the work floor only; therefore, the professionalization we described is informal. Yet, the informal professionalization process is inherently risky as it does not involve any change in the formal conditions of trial participants’ work. Instituting formal measures for protecting healthy trial participants as skilled workers combined with recognition of their expertise is essential.

Characteristics and outcomes of patients with gallbladder cancer and cholangiocarcinoma referred to a phase I clinic.

2012 ◽  
Vol 30 (4_suppl) ◽  
pp. 364-364 ◽  
Author(s):  
Ishwaria Mohan Subbiah ◽  
Vivek Subbiah ◽  
Ahmed Omar Kaseb ◽  
Filip Janku ◽  
Jennifer J. Wheler ◽  
...  
Keyword(s):  
Overall Survival ◽  
Clinical Trials ◽  
Phase I ◽  
Median Time ◽  
Median Survival ◽  
Phase I Trial ◽  
Mutational Analysis ◽  
Phase 1 ◽  
Cancer Center ◽  
Phase I Clinical Trials

364 Background: The prognosis of cholangiocarcinoma (CC) and gallbladder carcinoma (GC) remains grim. The purpose of this study was to report the presenting characteristics and outcomes of patients with CC and GC treated on phase 1 clinical trials focused on targeted agents at a major cancer center. Methods: We reviewed the records of consecutive patients with GC and CC in the Phase I Clinical Trials Program at the M. D. Anderson Cancer Center from Nov 2004. We assessed the relationship between overall survival, patients' tumor types, and mutations, demographic and clinical characteristics. Results: Fifty-two patients were identified (7 with GC, 45 with CC). The median age was 58 yrs (range, 20-75 yrs). ECOG performance status (PS) was 0, 1, 2, and 3 in 9 (17%), 30 (58%), 7 (13%), and 6 (12%) pts, respectively. Median number of prior therapies was 3 (range 0-17). The median time from diagnosis of metastatic disease to primary Phase I clinic evaluation was 14.6 months. Of 52 patients, 17 (33%) were not enrolled on a Phase I trial due to decline in PS (n=13) or decision to pursue other treatments (n=4). Of 35 patients evaluable for response, 2 (6%) had a partial response (PR), and 3 (9%) had stable disease > 4 months. Prognostic factors analyzed include Hg < 10.5 g/dL, elevated CA 19-9 (>47 ng/mL), ECOG PS > 3, LDH > 618 IU/L, albumin < 3.5 g/dL, platelets < 150 K/UL, and number of metastatic sites. Full analysis including the mutational analysis for PIK3CA, KRAS, BRAF, TP53 is in progress. Median survival since presentation to the Phase I clinic was 4.1 months (range 2.3 - 30.8 months). Median overall survival from diagnosis was 23.9 months. The median survival since enrollment in a Phase I trial was 4.6 months w the median time to disease progression on Phase I treatment was 2.2 months (range 0.6 - 25.6 months). Conclusions: Prognosis of pts with CC and GC referred for phase I studies remains poor. Further analysis including complete mutational profiles of CC and GC patients will be reported.

New immunotherapeutic drugs in advanced non-small cell lung cancer (NSCLC): from preclinical to phase I clinical trials

2020 ◽  
Vol 29 (9) ◽  
pp. 1005-1023
Author(s):  
Danilo Rocco ◽  
Vanesa Gregorc ◽  
Luigi Della Gravara ◽  
Chiara Lazzari ◽  
Giovanni Palazzolo ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Clinical Trials ◽  
Phase I ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase I Clinical Trials ◽  
Small Cell Lung

scholarly journals Tolerogenic dendritic cell-based treatment for multiple sclerosis (MS): a harmonised study protocol for two phase I clinical trials comparing intradermal and intranodal cell administration

BMJ Open ◽  
2019 ◽  
Vol 9 (9) ◽  
pp. e030309 ◽  
Author(s):  
Barbara Willekens ◽  
Silvia Presas-Rodríguez ◽  
MJ Mansilla ◽  
Judith Derdelinckx ◽  
Wai-Ping Lee ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Phase I ◽  
Unmet Need ◽  
Primary Objective ◽  
Attractive Alternative ◽  
Phase I Clinical Trials ◽  
Two Phase ◽  
Link Type

IntroductionBased on the advances in the treatment of multiple sclerosis (MS), currently available disease-modifying treatments (DMT) have positively influenced the disease course of MS. However, the efficacy of DMT is highly variable and increasing treatment efficacy comes with a more severe risk profile. Hence, the unmet need for safer and more selective treatments remains. Specifically restoring immune tolerance towards myelin antigens may provide an attractive alternative. In this respect, antigen-specific tolerisation with autologous tolerogenic dendritic cells (tolDC) is a promising approach.Methods and analysisHere, we will evaluate the clinical use of tolDC in a well-defined population of MS patients in two phase I clinical trials. In doing so, we aim to compare two ways of tolDC administration, namely intradermal and intranodal. The cells will be injected at consecutive intervals in three cohorts receiving incremental doses of tolDC, according to a best-of-five design. The primary objective is to assess the safety and feasibility of tolDC administration. For safety, the number of adverse events including MRI and clinical outcomes will be assessed. For feasibility, successful production of tolDC will be determined. Secondary endpoints include clinical and MRI outcome measures. The patients’ immune profile will be assessed to find presumptive evidence for a tolerogenic effect in vivo.Ethics and disseminationEthics approval was obtained for the two phase I clinical trials. The results of the trials will be disseminated in a peer-reviewed journal, at scientific conferences and to patient associations.Trial registration numbersNCT02618902andNCT02903537; EudraCT numbers: 2015-002975-16 and 2015-003541-26.

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