scholarly journals De‐risking Clinical Trials: The BIAL Phase I Trial in Foresight

2021 ◽  
Author(s):  
Adam F. Cohen ◽  
Jeroen van Smeden ◽  
David J. Webb
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase I Trial

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.

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.

Acceptability of tenofovir gel as a vaginal microbicide among women in a phase I trial a mixed-methods study,

2020 ◽  
Author(s):  
Lungwani Muungo
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Phase I Trial ◽  
Hiv Transmission ◽  
Sexual Transmission ◽  
Initial Product ◽  
Vaginal Microbicides ◽  
Tenofovir Gel ◽  
Gender Based ◽  
Sexual Transmission Of Hiv

THE GLOBAL HIV EPIDEMIC increasingly affectswomen.1 For most, the only risk factor for becominginfected is the behavior of their male sexualpartners.1 Condoms often are unacceptableand insufficiently used,2–4 gender-based powerimbalances can make them difficult to negotiate,4–7 and religious beliefs, fertility needs, fear ofimplied infidelity, and preferences for sex withouta barrier are challenges to their acceptabilityand use. Women-initiated HIV prevention methodsare urgently needed, making the developmentof vaginal microbicides that reduce the likelihoodof sexual transmission of HIV a majorpublic health priority.First-generation vaginal microbicides will mostlikely be topical gels inserted into the vagina withan applicator. A variety of microbicides is currentlyunder development, and six have enteredlate-stage clinical trials.8–12 Initial product acceptabilityhas been assessed in clinical trials,13–16 surveysof product attributes among potentialusers17,18 and their partners,19 and studies that useover-the-counter (OTC) surrogates or placebo gelwith presumed similar formulation and applicationcharacteristics as eventual products.20–23 Acceptabilityassessments in early clinical trials areespecially important because their findings can influencefurther development of the product.Here, we report on acceptability data amongwomen participating in a phase I trial of tenofovirgel, a candidate microbicide that inhibits HIV reversetranscriptase. Details of the trial are reportedelsewhere,24 as is acceptability amongmale partners of trial participants.25 This was thefirst human trial of a topical antiretroviral thatspecifically inhibits a necessary replication stepin the HIV life cycle. Interest in this approach toHIV prevention has increased in recent yearssince efficacy trials of a topical surfactant(nonoxynyl-9) and a nonspecific inhibitor of HIVbinding (cellulose sulfate) indicated that thesetwo types of compounds were not protective andpotentially increased HIV transmission in womenwho had frequent sexual exposures to HIV. Severallarger-scale, expanded safety and proof-ofconcepttrials of tenofovir gel are now underway,based in part on the safety, tolerability, and acceptabilityof this microbicide demonstrated inthe study described in this paper.

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.

Ingested Type I Interferon: State of the Art as Treatment for Autoimmunity

2002 ◽  
Vol 227 (11) ◽  
pp. 981-988 ◽  
Author(s):  
Staley A. Brod
Keyword(s):  
Rheumatoid Arthritis ◽  
Multiple Sclerosis ◽  
Clinical Trials ◽  
Type 1 Diabetes ◽  
Phase I ◽  
Phase I Trial ◽  
Type I Interferon ◽  
Type I ◽  
Ifn Γ

We have proposed a unifying hypothesis of the etiopathogenesis of autoimmunity that defines autoimmunity as a type I interferon (IFN) immunodeficiency syndrome. We have examined toxicity and potential efficacy in three phase I (type 1 diabetes, rheumatoid arthritis, multiple sclerosis) and one phase II clinical trials in multiple sclerosis. In a phase I open-label trial in type 1 diabetes, ingested IFN-α preserved residual β-cell function in recent onset patients. In a second phase I trial, treatment of rheumatoid arthritis with ingested IFN-α reduced the secretion of interleukin (IL)-1, a pro-inflammatory cytokine. In a third phase I trial in multiple sclerosis, there was a significant decrease in peripheral blood mononuclear cell IL-2 and IFN-γ production after ingesting IFN-α. In a phase II randomized, placebo-controlled, double-blind trial in multiple sclerosis, 10,000 IU ingested IFN-α significantly decreased gadolinium enhancements compared with the placebo group at month 5. Tumor necrosis factor-α and IFN-γ cytokine secretion in the 10,000 IU group at month 5 showed a significant decrease that corresponded with the effect of ingested IFN-α on decreasing gadolinium enhancements. Ingested IFN-α was not toxic in any of these clinical trials. These studies suggest that ingested IFN-α may have a potential role in the treatment of autoimmunity.

Assessment of quality of life using FACT-G survey in a phase I trial in cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e20709-e20709
Author(s):  
G. Jung ◽  
D. Knight ◽  
A. Moadel ◽  
K. Desai ◽  
I. Chaudhary ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Clinical Trial ◽  
Clinical Trials ◽  
Phase I ◽  
Phase I Trial ◽  
Statistical Significance ◽  
Well Being ◽  
Phase I Clinical Trials ◽  
The Mean

e20709 Background: Quality of life (QoL) assessment in clinical trials has been gaining more attention. FACT-G surveys have been validated to assess QoL in clinical trials involving oncology patient (Cella DF et al, J Clin Oncol 11:570–579, 1993). However, there is paucity of evaluation of QoL in patients with advanced cancer participating in Phase I clinical trials. Methods: FACT-G surveys were conducted within the context of a Phase I trial to identify a safe dose and potential drug-drug interations of capecitabine and irinotecan combination (Goel, S et al, Invest New Drugs 25:237–245, 2007). The FACT-G survey consists of 28 questions in 5 sections, namely, physical well-being, social/family well-being, emotional well-being, relationship with doctor, and functional well-being). Patients were requested to complete the FACT-G surveys at baseline and every two cycles thereafter (each cycle of 3 weeks duration). Results: Forty-one of 47 patients with advanced solid tumors who participated in the clinical trial completed FACT-G surveys. Mean scores were calculated for each time point. The mean QoL scores at baseline and post cycle 2 were 53 and 58, respectively (p = 0.1). Post cycle 4, the mean QoL score was 62 [p = 0.01, (vs. baseline)]. Following cycle 4, the number of respondents decreased to the extent where we were unable to ascertain any further changes in the QoL scores. Conclusions: It is feasible to use FACT-G survey as a tool to assess QoL in patients participating in an oncology phase I clinical trial. Although the sample size of the patient population was not powered for any statistical significance, there was a trend toward improving QoL based on FACT-G survey scores. This suggests that phase I clinical trials may provide improvement of QoL for some patients. FACT-G is a useful tool in assessing QoL in oncology phase I trial study population. No significant financial relationships to disclose.

Targeted agents matched with tumor molecular aberrations: Review of 160 patients with advanced melanoma treated in a phase I clinic.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8551-8551
Author(s):  
Haby Adel Henary ◽  
David S. Hong ◽  
Gerald Steven Falchook ◽  
Apostolia Maria Tsimberidou ◽  
Goldy George ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Systemic Therapy ◽  
Phase I Trial ◽  
Phase 1 ◽  
Targeted Agents ◽  
Phase I Clinical Trials ◽  
Kit Mutation ◽  
Targeted Agent ◽  
Molecular Aberrations

8551 Background: Identification of activating mutations in melanoma has increased the number of novel targeted agents for this disease. Methods: Weretrospectively reviewed clinical outcomes of 160 consecutive metastatic melanoma patients (pts) treated in the Dept of Investigational Cancer Therapeutics (Phase I program) at M. D. Anderson since 2008, and compared their median progression free survival (PFS) to their first and last standard systemic therapy PFS. In addition, we compared those pts’ outcomes tested for tumor molecular aberrations on a phase I trial with a matched targeted agent with those of pts who were treated without regard for their molecular profiles. Results: Of 160 pts treated on 35 different phase 1 clinical trials, 110 pts (69%) had ≥ 1 molecular aberration. Of those pts who had adequate tissue for molecular analysis, 63% (85/134) pts had BRAF mutation, 20% (22/109) NRAS mutation, 20% (1/5) GNAQ mutation, 11% (1/9) P53 mutation, 2.5% (1/39) PIK3CA and 1.3% (1/76) had KIT mutation. 77 (48%) pts were treated on a phase I trial with a matched targeted agent and 83 (52%) pts were treated on a non-matched phase 1 trial. The overall response rate was 39% (complete response [CR], 9%; partial response [PR], 30%) in the 77 pts treated with matched therapy and 9% (all PRs) in the 83 pts treated without matched therapy (P = 0.0018). 139 (87%) pts received at least one systemic therapy before referral to phase I, median PFS was longer on phase 1 therapy than on last line standard therapy prior to referral to phase 1 (4.2 vs. 2.8 months, P = 0.002). Median PFS was greater for pts on matched vs. non-matched therapy (5.3 vs. 3.7 months, log rank P = 0.004). Also, median PFS was longer on phase 1 matched trial than on first standard treatment (5.3 vs. 3.9 months, log rank P = 0.045).PFS did not differ between first standard and non-matched phase 1 study. Univariate analyses with the log rank test revealed that matched therapy (P = 0.004) was positively associated with longer PFS on phase I clinical trials. Conclusions: Matching melanoma pts with targeted drugsbased on specific molecular aberrations in the phase I setting can be associated with superior outcomes compared to prior standard systemic therapies.

scholarly journals Novel Therapies for the Treatment of Patients with Relapsed/Refractory Multiple Myeloma: A Review of Clinical Trials

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 43-44
Author(s):  
Ahmad Iftikhar ◽  
Muhammad Ahmad ◽  
Pranali Pachika ◽  
Faryal Razzaq ◽  
Muhammad Ashar Ashar Ali ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
T Cell ◽  
Cell Therapy ◽  
Phase I ◽  
Phase I Trial ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T Cell Therapy ◽  
Car T

Introduction: Multiple myeloma (MM) is a neoplastic proliferation of plasma cells. It is the second most common hematological malignancy in the US. Although it is associated with poor prognosis, newer therapies have improved outcomes in MM patients. This review aims to describe novel therapies used for the treatment of relapsed/refractory multiple myeloma (RRMM). Methods: A literature search was performed on Embase and clinicaltrials.gov using the keyword "Multiple Myeloma" from 1/1/2016 to 6/25/2020 for identifying ongoing clinical trials in the treatment of RRMM. After detailed scrutiny, we included 23 ongoing clinical trials (N=4362). We excluded case reports, case series, review articles, meta-analysis, and observational studies. Results: We summarized the interim results from ongoing clinical trials evaluating treatment of RRMM under following newer categories of drugs: Immunomodulatory drugs In a phase 1b/IIa trial (NCT02773030, N=51) evaluating the efficacy of a novel immunomodulators, iberdomide CC-220 + dexamethasone (Dex) yielded an overall response rate (ORR) of 31%, clinical benefit (CB) was seen in 51% of the patients, and disease control (DC) in 88% of the patients and it was well tolerated by RRMM patients. There are other ongoing clinical trials evaluating the efficacy of Avadomide (CC-122), CC-92480 in RRMM. Alkylating agents In a phase I/II trial (NCT01897714, N=45), melphalan-flufenamide (melflufan) + Dex yielded an ORR of 31%, it was well tolerated with 49% CB. Phase III OCEAN trial (NCT03151811, N=450) is currently ongoing to compare melflufen + Dex vs. pomalidomide (Pom) + Dex. Apoptotic agents A phase 3 trial BELLINI (NCT02755597, N=291) evaluated the efficacy of veneteclox (Ven, Bcl-2 inhibitor) by randomizing patients to either Ven or Placebo arm. With a median follow up of 28.6 months (m), progression free survival (PFS) was 23.2m in the Ven arm vs. 11.4m in placebo. The interim results from a phase I/II trial (NCT03314181, N=104) of Ven + daratumumab (Dara) + Dex showed ORR of 96% with ≥ very good partial response (VGPR) of 96%. The addition of Bortezomib (Bor) to VenDaraDex had a slightly low ORR of 92%, with ≥VGPR of 79%. Another phase I/II trial (NCT01794520, N=117) is in progress to assess the efficacy and safety of Ven as monotherapy. Monoclonal Antibodies (MoAb) A phase I/II trial (NCT01421186, N=91) evaluated the efficacy of MOR202, which is a novel MoAb. MOR202 was evaluated in three arms; MOR202 + Dex, MOR202 + Lenalidomide (Len) + Dex and MOR202 + Pom + Dex. The interim analysis showed the ORR of 65% with MOR202 + Len + Dex which was better than ORR of 48% with MOR202 + Pom + Dex, while the use of MOR202 + Dex yielded only 28% ORR. Antibody-drug conjugate (ADC) Four ongoing trials are evaluating the efficacy of ADC (belantamab mafodotin), and the interim results are available for two trials. In phase II DREAMM-2 trial (NCT03525678, N=221) evaluating 2 doses of GSK2857916, 2.5mg/kg dose yielded ORR of 31% while 3.4mg/kg showed ORR of 34%. Another phase I trial (NCT02064387, N=79) evaluated belantamab mafodotin in RRMM and other hematologic malignancies expressing B-cell maturation antigen (BCMA). The results were promising with ORR of 60%. Bispecific T-cell engagers (BiTE) Phase I trial of BiTE AMG 420 (NCT02514239, N=43) showed favorable results with ORR 70%, and CR 12%. The interim results from another phase I trial (NCT03486067, N=115) which evaluated the efficacy of BiTE CC-93269 showed 43% ORR and CR 17%. CAR-T Cell therapy CAR-T cell therapy is also being studied in RRMM with JNJ-68284528 directed against BCMA in a phase Ib trial (NCT03548207, N=118). The interim analysis of 29 response evaluable patients out of 118 reported 100% ORR with stringent CR 76%. PK13 Inhibitors In a phase I/II study (NCT00401011, N=84) evaluating perifosine + Bor +/- Dex, ORR of 41% was observed in Bor RR patients, and therapy was well tolerated with PFS of 6.4m and mOS of 25m. Conclusion: This review demonstrates novel and promising therapies which are currently in early phase clinical trials for the treatment of RRMM. Based on interim results, Iberdomide, melflufan, Ven, MoAb MOR202, ADC belantamab mafodotin, BiTE Molecule AMG 420, BCMA CAR-T cell therapy and perifosine have shown promising early activity and safety data in RRMM patients. Additional exploratory clinical trials are needed to confirm the efficacy and safety of these agents. Disclosures Anwer: Incyte, Seattle Genetics, Acetylon Pharmaceuticals, AbbVie Pharma, Astellas Pharma, Celegene, Millennium Pharmaceuticals.: Honoraria, Research Funding, Speakers Bureau.

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