Association of serious adverse events with type and sponsorship of clinical trials in patients with lymphoma

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 6576-6576
Author(s):  
T. L. Koeneke ◽  
J. O. Armitage ◽  
P. J. Bierman ◽  
R. Bociek ◽  
J. M. Vose ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Phase Ii ◽  
Medical Center ◽  
Stage Iv ◽  
Large Cell ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Early Phase Clinical Trials

6576 Background: Arguments have been made against early phase clinical trials (CTs) as possibly being unethical because its risk may outweigh its potential benefits. Whether this is true in the light of newer biological treatment for cancer is unknown. We therefore examined the association between the incidence of serious adverse events according to type and sponsorship of CTs in pts with lymphoma. Methods: All IRB approved CTs at the University of Nebraska Medical Center from Jan 2000-June 2005 classified as therapeutic for lymphoma involving a biological agent were included. CTs were classified in two ways: by type of CTs (phase I vs II vs III) and sponsorship (Investigator-initiated vs Industry-initiated. Multivariate logistic regression was used to evaluate the association between types/sponsorship of CTs with the incidence of IRB serious adverse events (SAE; no vs yes) and fatal adverse events (FAE; no vs yes) while adjusting for age, sex, race, lymphoma type and stage, interval from dx to tx, co-morbid conditions, and previous tx. Results: 357 pts with lymphoma enrolled in 29 CTs were included. The median age of pt was 54y (21–88). 41% of the pts had follicular lymphoma, 36% diffuse large cell, 14% mantle cell and 9% were other types. 59% had Stage IV lymphoma. 71% of the pts participated in investigator-initiated CTs, while 29% participated in industry-initiated CTs. 21% of pts were enrolled in phase I, 65% in phase II and 14% in phase III studies. SAEs were seen in 49 pts (14%), while FAEs occurred in 13 pts (4%). Multivariate analysis showed the risk of having SAE was independent of the type or sponsor of CTs. Additionally, the risk of FAEs was not associated with the type of CTs. However, the risk of having FAEs was less in investigator- iniatiated CTs than in industry-iniatiated trials (Odds Ratio: 0.13 (95% CI, 0.03–0.61, p = 0.01). Conclusions: Our study showed that in CTs involving biological treatments, the incidence of SAEs was not associated with the type or sponsor of CTs suggesting that use of biological agents in phase I studies may have similar risks to phase II/III trials. Further studies should be done in other types of malignancies to evaluate further the decrease frequency of FAEs seen in investigator-initiated trials. No significant financial relationships to disclose.

scholarly journals Unconventional Anticancer Agents: A Systematic Review of Clinical Trials

2006 ◽  
Vol 24 (1) ◽  
pp. 136-140 ◽  
Author(s):  
Andrew J. Vickers ◽  
Joyce Kuo ◽  
Barrie R. Cassileth
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Cancer Patients ◽  
Phase Ii ◽  
Dose Finding ◽  
Phase Iii ◽  
High Dose ◽  
Free Text ◽  
Phase Ii Trials ◽  
Off Label

Purpose A substantial number of cancer patients turn to treatments other than those recommended by mainstream oncologists in an effort to sustain tumor remission or halt the spread of cancer. These unconventional approaches include botanicals, high-dose nutritional supplementation, off-label pharmaceuticals, and animal products. The objective of this study was to review systematically the methodologies applied in clinical trials of unconventional treatments specifically for cancer. Methods MEDLINE 1966 to 2005 was searched using approximately 200 different medical subject heading terms (eg, alternative medicine) and free text words (eg, laetrile). We sought prospective clinical trials of unconventional treatments in cancer patients, excluding studies with only symptom control or nonclinical (eg, immune) end points. Trial data were extracted by two reviewers using a standardized protocol. Results We identified 14,735 articles, of which 214, describing 198 different clinical trials, were included. Twenty trials were phase I, three were phase I and II, 70 were phase II, and 105 were phase III. Approximately half of the trials investigated fungal products, 20% investigated other botanicals, 10% investigated vitamins and supplements, and 10% investigated off-label pharmaceuticals. Only eight of the phase I trials were dose-finding trials, and a mere 20% of phase II trials reported a statistical design. Of the 27 different agents tested in phase III, only one agent had a prior dose-finding trial, and only for three agents was the definitive study initiated after the publication of phase II data. Conclusion Unconventional cancer treatments have not been subject to appropriate early-phase trial development. Future research on unconventional therapies should involve dose-finding and phase II studies to determine the suitability of definitive trials.

scholarly journals Focusing on the Treatment of COVID-19: A Comprehensive Analysis of 226 Trials Registered on Clinicaltrials.gov and ChiCTR

2021 ◽  
Author(s):  
Jincai Guo ◽  
Hui Xie ◽  
Hao Wu
Keyword(s):  
Clinical Trials ◽  
Chinese Medicine ◽  
Phase I ◽  
Phase Ii ◽  
Western Medicine ◽  
Phase Iii ◽  
Phase Ii Trials ◽  
Double Blind ◽  
Intervention Measures ◽  
Chinese Medicine Treatment

Abstract Background: The purpose of this study is to analyze the registered clinical trials of COVID-19, and to provide a reference for the clinical treatment of COVID-19. Methods: Chinese ClinicalTrial Registry (ChiCTR) and Clinicaltrials.gov databases were searched for clinical trials of COVID-19, which were registered from inception to February 29, 2020, to screen out the clinical trials on the treatment of COVID-19, and the research units and regions, sample size, study types, study stages, and intervention measures were analyzed. Results: There were 226 clinical trials on COVID-19 in the 2 databases, and all of them were registered by research units in China. The top five registered areas were Hubei, Beijing, Shanghai, Guangdong, and Zhejiang. The study type was as follows: interventional study (207, 91.6%) and observational study (18, 8.0%). Clinical trial staging was as follows: exploratory studies/preliminary trials (91, 40.3%), phase I trials (4, 1.8%), phase II trials (12, 5.3%), phase III trials (12, 5.3%), phase IV trials (47, 20.8%), phase I/II trials (2, 0.9%), phase II/III trials (5, 2.2%), and other trials (57, 25.2%). Intervention measures were as follows: there were 143 (63.3%) trials of western medicine treatment, 50 (22.1%) trials of Chinese medicine treatment, and 21 (9.3%) trials of integrated Chinese medicine treatment and western medicine treatment. Conclusion: Researchers have registered a large number of clinical trials in a short time. The number of existing patients of COVID-19 is not enough to support hundreds of clinical trials. There is a lack of multicenter, randomized, double-blind, placebo-controlled trials.

scholarly journals Efficacy and Safety of Histone Deacetylase Inhibitors in Multiple Myeloma - a Systematic Review of Early Phase Clinical Trials

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5629-5629
Author(s):  
Sharoon Samuel ◽  
Muhammad Junaid Tariq ◽  
Muhammad Usman ◽  
Amna Khalid ◽  
Muhammad Asad Fraz ◽  
...  
Keyword(s):  
Systematic Review ◽  
Multiple Myeloma ◽  
Clinical Trials ◽  
Adverse Events ◽  
Phase I ◽  
Hdac Inhibitors ◽  
Complete Response ◽  
Number Of Patients ◽  
Grade 3 ◽  
Early Phase Clinical Trials

Abstract Introduction Recent studies in novel therapies have created opportunities for new treatment regimens to be used in the management of multiple myeloma. Histone deacetylase (HDAC) inhibitors lead to epigenetic manipulation of multiple myeloma (MM) cells by reducing resistance to pro-apoptotic signals. Panobinostat is an FDA approved HDAC inhibitor for multiple myeloma. The aim of this article is to study the safety, efficacy and dose limiting toxicities of HDAC inhibitors in the early phase clinical trials in multiple myeloma. Methods We performed a comprehensive literature search for phase I & I/II trials of HDAC inhibitors during last ten years using following databases: PubMed, Embase, AdisInsight, and Clinicaltrials.gov. Studies involving HDAC inhibitors in multiple myeloma other than panobinostat irrespective of the age, sex or specific eligibility criteria were included. Results Out of 2537 studies, we included 25 trials (23 phase I, 2 phase I/II) of HDAC inhibitors in this systematic review having a total of 518 patients. Of these, 471(90.9%) patients were evaluable for response. Vorinostat (Vor) is the most studied drug used in 13 trials (n=281). Two trials had Vor-only regimen and the remaining 11 had combination regimens mostly with lenalidomide and bortezomib. Vor, in combination with lenalidomide (R), bortezomib (V) and dexamethasone (d) has showed 100% overall response rate (ORR) in 30 newly diagnosed multiple myeloma (NDMM) patients, (Kaufmann et al., 2016), fifty two percent patients achieved very good partial response (VGPR) and 28% patients showed complete response (CR). Another study using Vor + R regimen after autologous stem cell transplant in 16 NDMM patients showed VGPR in 7, stringent complete response (sCR) in 4, partial response (PR) in 2 and CR in 3 patients (Sborov et al.). Grade 3 neutropenia was seen in 1 patient in this study. Richter et al, 2011 showed an ORR of 24% in 29 relapsed refractory multiple myeloma (RRMM) patients with Vor only regimen. Another study (Kaufmann et al., 2012) with Vor only regimen used in 10 RRMM patients showed stable disease (SD) in 9 and minimal response (MR) in 1 patient. ORR of 65% was achieved in 31 RRMM patients receiving Vor in combination with doxorubicin & bortezomib (Vorhees et al, 2017). Thrombocytopenia & neutropenia were reported in 94% and 59% patients respectively. Ricolinostat in combination with Rd and Vd achieved an ORR of 55% and 29% respectively in two studies with 38 and 57 evaluable patients (NCT01583283, NCT01323751). Another ricolinostat regimen with pomalidomide & dexamethasone achieved ≥PR in 6/11 RRMM patients (Madan et al., 2016). Table 1 illustrates the efficacy, number of patients and regimens used in all the studies in this systematic review. Quisinostat in a 2017 study by Moreau P et al. (NCT01464112) showed an ORR of 88% in a combination regimen with Vd in RRMM patients (N=18). Drug related adverse events were seen in 13 patients, thrombocytopenia being most common in 11 patients, 2 patients had grade 3 cardiac disorders and 1 patient had a cardiac arrest. Romidepsin in a phase I/II study (Harrison et al., 2011) combined with Vd was used in 25 RRMM patients. ORR was 60% with VGPR n=7, CR n=2, PR n=6, SD n=5 and PD n=1. Grade ≥3 thrombocytopenia in 16, neutropenia in 9 and peripheral neuropathy in 2 patients was seen. Popat et al used combination of two HDAC inhibitors CHR 3996 and tosedostat in 20 RRMM patients. ORR was 10% and SD was seen in 30% patients. Grade 3/4 toxicities seen were thrombocytopenia (n=12), leukopenia (n=6) and diarrhea (n=5). A phase I study on AR-42 drug in 17 RRMM patients (Sborov et al., 2017) showed SD in 10, PD in 4, MR in 3 patients with progression free survival (PFS) of 8.2 months. Thrombocytopenia, neutropenia and lymphopenia were seen in 11, 10 and 6 patients respectively. A detail of all grade 3 and higher adverse events along with dose limiting toxicity is given in table 2. Three trials (NCT02576496, NCT01947140, NCT03051841) of Edo-S101, romidepsin and CKD-581 are currently recruiting with 84, 93 and 18 planned number of patients. Conclusion Regimens containing vorinostat have shown an ORR up to 100% in NDMM patients. HDAC inhibitors have also shown promising efficacy up to 88% ORR in RRMM population. Majority of the patients developed cytopenias as hematological adverse events. Disclosures No relevant conflicts of interest to declare.

Established and In-trial GPCR Families in Clinical Trials: A Review for Target Selection

2019 ◽  
Vol 20 (5) ◽  
pp. 522-539 ◽  
Author(s):  
Surovi Saikia ◽  
Manobjyoti Bordoloi ◽  
Rajeev Sarmah
Keyword(s):  
Clinical Trials ◽  
Drug Discovery ◽  
Phase I ◽  
Human Genome ◽  
Phase Ii ◽  
Drug Targets ◽  
Complex Diseases ◽  
Phase Iii ◽  
Computational Techniques ◽  
Receptor Complexes

The largest family of drug targets in clinical trials constitute of GPCRs (G-protein coupled receptors) which accounts for about 34% of FDA (Food and Drug Administration) approved drugs acting on 108 unique GPCRs. Factors such as readily identifiable conserved motif in structures, 127 orphan GPCRs despite various de-orphaning techniques, directed functional antibodies for validation as drug targets, etc. has widened their therapeutic windows. The availability of 44 crystal structures of unique receptors, unexplored non-olfactory GPCRs (encoded by 50% of the human genome) and 205 ligand receptor complexes now present a strong foundation for structure-based drug discovery and design. The growing impact of polypharmacology for complex diseases like schizophrenia, cancer etc. warrants the need for novel targets and considering the undiscriminating and selectivity of GPCRs, they can fulfill this purpose. Again, natural genetic variations within the human genome sometimes delude the therapeutic expectations of some drugs, resulting in medication response differences and ADRs (adverse drug reactions). Around ~30 billion US dollars are dumped annually for poor accounting of ADRs in the US alone. To curb such undesirable reactions, the knowledge of established and currently in clinical trials GPCRs families can offer huge understanding towards the drug designing prospects including “off-target” effects reducing economical resource and time. The druggability of GPCR protein families and critical roles played by them in complex diseases are explained. Class A, class B1, class C and class F are generally established family and GPCRs in phase I (19%), phase II(29%), phase III(52%) studies are also reviewed. From the phase I studies, frizzled receptors accounted for the highest in trial targets, neuropeptides in phase II and melanocortin in phase III studies. Also, the bioapplications for nanoparticles along with future prospects for both nanomedicine and GPCR drug industry are discussed. Further, the use of computational techniques and methods employed for different target validations are also reviewed along with their future potential for the GPCR based drug discovery.

Pacritinib, a Dual JAK2/FLT3 Inhibitor: An Integrated Efficacy and Safety Analysis Of Phase II Trial Data In Patients With Primary and Secondary Myelofibrosis (MF) and Platelet Counts ≤100,000/µl

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 395-395 ◽  
Author(s):  
Srdan Verstovsek ◽  
James P. Dean ◽  
Paul Cernohous ◽  
Rami S Komrokji ◽  
John F. Seymour ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Platelet Count ◽  
Adverse Events ◽  
Phase I ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Spleen Volume ◽  
Myeloid Malignancies ◽  
Platelet Counts ◽  
Flt3 Inhibitor

Abstract Background and Aims A platelet count ≤100,000/µL is regarded as an independent prognostic marker for the development of leukemia and is associated with inferior survival in myelofibrosis (MF) (Huang et al. 2008). The approved JAK2 inhibitor, ruxolitinib, is associated with treatment-emergent thrombocytopenia, and patients with platelets ≤100,000/µL were excluded from the phase III COMFORT trials. Efficacy and safety data are limited in patients with MF and platelets ≤100,000/µL treated with ruxolitinib. Pacritinib (SB1518), an oral JAK2/FLT3 inhibitor, did not appear to be associated with clinically significant treatment emergent anemia or thrombocytopenia during early phase studies in patients with myeloid and lymphoid malignancies. This integrated analysis was performed to further evaluate the safety and efficacy of pacritinib in MF patients with baseline platelet counts of ≤100,000/µL. Methods The databases from 2 phase I/II clinical trials of pacritinib in advanced myeloid malignancies and MF were integrated to evaluate the rate of adverse events (AEs) and favorable spleen responses in patients with MF and thrombocytopenia. Results One hundred twenty-nine patients with advanced myeloid malignancies and MF were treated with pacritinib in phase I and II clinical trials. Sixty-five patients with MF were treated with 400 mg orally once daily in 2 phase II studies. Of these, 28 patients with MF [21 primary MF (75%), 5 post-polycythemia vera-MF, 2 post-essential thrombocytosis-MF] had baseline platelet counts of ≤100,000/µL (median: 58,500/µL, range: 15,000/µL – 97,000/µL). The median age was 69 years. Twenty three (82%) patients had the JAK2V617F mutation. During the phase 2 studies, spleen volume responses were assessed by MRI and are shown for all patients (Figure 1) and for patients with platelets ≤100,000/µL (Figure 2). Thirty-seven percent and 43% of all evaluable patients and patients with ≤100,000/µL platelets, respectively, had ≥35% reduction in spleen volume from baseline (Table). Among the 21 informative patients with allelic JAK2V617F quantification at more than 1 study visit, 3, including 2 patients with homozygous mutations, had ≥35% reduction in spleen volume and substantial reductions in allelic burden from baseline (mean reduction 64%, range 44 to 88%). In the 11 (17%) patients with MF and baseline platelet counts ≤50,000/μL, overall spleen volume reduction was 38% (3/8) in evaluable patients and the median decline in platelet count observed at study end was 6,000/µL. Integrated safety analysis for all 129 patients with advanced myeloid malignancies showed the most common adverse events (AEs) were gastrointestinal (GI), predominantly diarrhea, and most of these were grade 1 (43%) and grade 2 (26%). The time to onset of diarrhea was ≤30 days in the majority of those affected, but only 2% had drug discontinuation as a consequence. Among the 129 patients in the phase 1 and 2 trials, 57 patients had ≤100,000 platelets; of these 26 (46%) had no CTC grade change in hemoglobin (Hb) and platelet counts from baseline values. Hb and platelet counts improved by one grade in 16% and 18% of patients, respectively. One grade worsening was seen in 28% and 30% in Hb and platelet counts, respectively. Conclusions Pacritinib was well-tolerated in patients with MF, regardless of their baseline platelet counts. Grade 1 or 2 GI toxicities, particularly diarrhea, were the most common AEs. Spleen responses were similar in patients regardless of baseline platelet counts (≥100,000/µL vs. ≤100,000/µL). Notably, even patients with initial platelet counts ≤50,000/µL tolerated therapy and the majority maintained stable hemoglobin and platelet counts. A phase III trial will evaluate pacritinib versus best available therapies in patients with MF and platelet counts ≤100,000/µL. Disclosures: Dean: Cell Therapeutics, Inc: Employment. Cernohous:Cell Therapeutics, Inc: Employment. Mesa:Incyte, CTI, Gilead, Celgene, Genetech, NS Pharma, Lilly: Research Funding. Campbell:Cell Therapeutics, Inc: Employment. Caldwell:Cell Therapeutics, Inc: Employment. Wang:Cell Therapeutics, Inc.: Employment. Myint:Cell Therapeutics, Inc: Employment.

The safety profile of eltrombopag, a novel oral platelet growth factor, in thrombocytopenic patients and healthy subjects

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 18596-18596 ◽  
Author(s):  
D. Provan ◽  
M. Saleh ◽  
S. Goodison ◽  
R. Rafi ◽  
N. Stone ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Phase Ii ◽  
Platelet Function ◽  
Healthy Subjects ◽  
Clinical Laboratory ◽  
Serious Adverse Events ◽  
Parallel Group ◽  
Apparent Relationship ◽  
Tolerability Data

18596 Background: Eltrombopag (SB-497115) is an oral, non-peptide, small molecule, thrombopoietin receptor agonist being tested as a potential treatment for thrombocytopenia. Eltrombopag has been shown to increase platelet counts in both healthy subjects and thrombocytopenic patients. Methods: Safety and tolerability data for eltrombopag (3–75 mg for up to 6 weeks) is presented from randomized, placebo-controlled, parallel group clinical trials involving 115 healthy subjects and 104 immune thrombocytopenic purpura (ITP) patients. Safety and tolerability endpoints involved assessment of adverse events (AE) and clinical laboratory parameters, including ECGs and platelet function. Results: In 3 Phase I trials, 98 healthy males received active eltrombopag QD for up to 10 days at 3–75 mg. In the Phase II dose ranging study, 78 chronic ITP patients (28 male/50 female) received active eltrombopag QD for 6 weeks at doses of 30–75 mg. There was no apparent relationship between active and control arms, the dose of eltrombopag and the incidence or severity of AEs, changes in laboratory values, platelet function or cardiac parameters in any of the studies. There were no serious adverse events (SAEs) reported by subjects in the 3 Phase I studies. 5 SAEs were reported in 1 patient in the ITP study that were considered by the investigator as possibly associated with administration of 50 mg eltrombopag. No SAEs were related to 30 mg or 75 mg eltrombopag, and 2 SAEs in 2 patients were related to placebo. Conclusions: There was no apparent relationship between eltrombopag dose and safety endpoints in these studies. These encouraging safety and tolerability data support the further testing of eltrombopag in phase II and III studies involving patients with ITP and chronic liver disease, and cancer patients receiving thrombocytopenic chemotherapy. [Table: see text]

A phase I trial of a local delivery of siRNA against k-ras in combination with chemotherapy for locally advanced pancreatic adenocarcinoma.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 4037-4037 ◽  
Author(s):  
Talia Golan ◽  
Ayala Hubert ◽  
Amotz Shemi ◽  
Amiel Segal ◽  
Alan Dancour ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase I ◽  
Pancreatic Adenocarcinoma ◽  
Phase Ii ◽  
Locally Advanced ◽  
Primary Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Line Setting

4037 Background:K-Ras mutation G12D is most prevalent in pancreatic adenocarcinoma (PDAC). siRNA against the K-RasG12D(siG12D) mutant had showed significant preclinical anti-tumor effects. siG12D LODER - miniature biodegradable polymeric matrix that encompasses anti-K-RasG12D siRNA drug, is placed with Endoscopic US biopsy and designed to continuously release the drug regionally over a period of 4 months. Methods: Open label phase I study of patients with locally advanced non-operable PDAC in the first-line setting. Patients were assigned to receive siG12D LODERs in dose escalation cohorts: 0.025mg, 0.75mg and 3.0mg. Gemcitabine 1000 mg/m2IV was given weekly, following siG12D LODER insertion. The RP2D (recommended phase II dose) was further examined in 3.0 mg dose cohort in combination with modified Folfirinox (Oxaliplatin 85mg/m2, Irinotecan 150mg/m2, Fluorouracil infusion 2,400mg/m2 46 hours, every 2 weeks). Follow up period was 8 weeks and survival follow up until death. Primary study objectives were to determine the dose-limiting toxicities (DLT) and maximum tolerated doses (MTD). Results:15 patients have been enrolled. 2 patients were omitted from study due to metastatic disease detected on day 1 post siG12D LODER implant imaging . Median age = 70 (range 52-85); male:female 8:7. Among 13 treated patients, the most frequent adverse events observed in the study were typically grade 1- 2 in severity; 4 patients experienced serious adverse events (SAE), one procedure related. No DLTs were observed. MTD was not reached. CT performed 8-10 weeks following the procedure showed stable disease in all patients. Reduction in tumor marker CA 19-9 was observed in 64% (7/11) of patients. The median survival of 13 patients was 16 months ( 8/13 patients still alive at analysis). Conclusions: The combination of siG12D LODER and chemotherapy is well tolerated. The combination has demonstrated promising efficacy in locally advanced PDAC with durable responses. Phamocodynamic endpoints are currently being examined in an expansion cohort in operable patients. A phase II randomized trial is planned in order to investigate efficacy of siG12D LODER in locally advanced non-operable PDAC. Clinical trial information: NCT01188785.

Pooled safety analysis of single-agent lurbinectedin versus topotecan (Results from a randomized phase III trial CORAIL and a phase II basket trial).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3635-3635
Author(s):  
Alexandra Leary ◽  
Stephanie Gaillard ◽  
Ignace Vergote ◽  
Jose Trigo ◽  
Carmen Maria Kahatt ◽  
...  
Keyword(s):  
Adverse Events ◽  
Phase Ii ◽  
Single Agent ◽  
Primary Prophylaxis ◽  
Safety Analysis ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Active Transcription ◽  
Basket Trial ◽  
Grade 3

3635 Background: Lurbinectedin (L), an inhibitor of active transcription, has shown activity in second-line (2L) small cell lung cancer (SCLC) (ASCO 2019). Topotecan (T) is the only approved drug in 2L SCLC and is also used in platinum resistant ovarian cancer (PROC). Methods: This pooled safety analysis includes data from 554 patients (pts) treated with L at 3.2 mg/m2 Day 1 q3wk 1-h (no primary prophylaxis with G-CSF required): 335 with selected solid tumors (9 indications, including 105 pts with SCLC) from a phase II Basket study and 219 with PROC in the phase III CORAIL study. An indirect exploratory comparison (pooled data from CORAIL + Basket) and a direct comparison (data from CORAIL) of L vs. T are presented. Results: Most common adverse events with L were grade 1/2 fatigue, nausea and vomiting. Treatment-related (L/T): dose reductions: 22.9/48.3%, delays: 25.8/52.9%, grade ≥3 serious adverse events (SAEs): 15.0/32.2%, discontinuations: 3.2/5.7%, deaths: 1.3/1.5%, G-CSF use: 23.8/70.1%, and transfusions: 15.9/52.9%. Conclusions: Lurbinectedin has a predictable and manageable safety profile. A significant safety advantage was observed when lurbinectedin was compared with topotecan in the CORAIL trial in terms of hematological toxicities. With the limitations of indirect comparisons, in the pooled safety analysis, fewer lurbinectedin-treated pts had severe hematological toxicities, SAEs, dose adjustments, treatment discontinuations and use of supportive treatments than topotecan-treated pts. Clinical trial information: NCT02421588 and NCT02454972 . [Table: see text]

scholarly journals Therapeutic outcome of early-phase clinical trials in multiple myeloma: a meta-analysis

2021 ◽  
Vol 11 (3) ◽  
Author(s):  
Niels van Nieuwenhuijzen ◽  
Rowan Frunt ◽  
Anne M. May ◽  
Monique C. Minnema
Keyword(s):  
Multiple Myeloma ◽  
Clinical Trials ◽  
Phase I ◽  
Phase Ii ◽  
Early Phase ◽  
Meta Analysis ◽  
Cochrane Library ◽  
Phase I Trials ◽  
Phase Ii Trials ◽  
Early Phase Clinical Trials

AbstractGreat progress in the treatment of patients with multiple myeloma (MM) has been made due to the development of novel drugs. Patients with relapsed/refractory MM (RRMM) can be enrolled in early-phase clinical trials, but their performance across the last decade is unknown. We conducted a meta-analysis on the overall response rate (ORR) and toxicity. PubMed, Embase, and Cochrane Library were systematically searched for phase I and phase II trials investigating an experimental compound as a single agent or in combination with dexamethasone, published from January 1, 2010 to July 1, 2020. Eighty-eight articles were included, describing 61 phase I trials involving 1835 patients and 37 phase II trials involving 2644 patients. There was a high degree of heterogeneity. Using a random-effects model, the 95% CIs of the estimated ORR were 8–17% for phase I trials and 18–28% for phase II trials. There were significant subgroup differences in ORR between the years of publication in phase I trials and between drug classes in both phase I and phase II trials. The ORR in early-phase clinical trials in RRMM is substantial, especially in phase II trials, but due to high heterogeneity a general assessment of clinical benefit before participation is difficult to offer to patients.

Sown the seeds: An analysis of published trials in clinical oncology.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 6068-6068
Author(s):  
Natalie M. Spradlin ◽  
David H. Johnson ◽  
Leora Horn
Keyword(s):  
Clinical Trials ◽  
Phase I ◽  
Clin Oncol ◽  
Phase Ii ◽  
High Impact ◽  
Phase Iii ◽  
Major Market ◽  
Therapeutic Class ◽  
Disease Site ◽  
Pubmed Search

6068 Background: Competition in the pharmaceutical marketplace has resulted in “seeding trials” which appear to serve little scientific purpose other than to gain a financial hold in the marketplace. Hallmarks of “seeding” clinical trials [Kessler, et al N Eng J Med 1994] include trial design that does not support stated research goals, industry sponsorship without novel findings or poor scientific rationale, and drugs introduced into an already crowded therapeutic class, i.e. “me too” drugs. We evaluated clinical trials published in high impact oncology journals to ascertain the prevalence of trials bearing the characteristics of a seeding trial. Methods: We conducted a PubMed search using “clinical trial”, “oncology”, published 2/2005 – 2/2010, in Ann Oncol, J Clin Oncol, Lancet, Lancet Oncol, or the N Engl J Med. All phase I/II, II and III studies were included. Phase I, hematology, radiation oncology, and pediatric studies were excluded. Data collected included disease site, phase, funding source, journal, and whether the trial fit criteria for “seeding” as previously defined. Results: 1781 articles have been evaluated to date. 528 met criteria for analysis. 130 were considered seed studies. Seed studies per journal were Ann Oncol 26 of 128, J Clin Oncol 88 of 340, Lancet 8 of 22, Lancet Oncol 5 of 16, and N Engl J Med 3 of 22. Studies published per disease site and percent seed studies were melanoma 19 and 31.6%, breast 106 and 30.2%, GI 126 and 20.6%, lung 101 and 29.7%, GU 65 and 24.6%, gynecology 40 and 30%, head and neck 24 and 12.5%, CNS 24 and 12.5%, sarcoma 11 and 18.2%, and advanced cancer 12 with zero seeds. Overall phase totals were phase I/II 16, phase II 272, and phase III 240. Seed studies per phase were phase II 28.7%, phase III 21.7% and zero for phase I/II. 210 studies were solely industry sponsored, and of these, 37.1% were seed studies. Funding was not listed for 73 studies. Conclusions: The integrity of clinical trials is challenged in the race to claim major market share. Our analysis of clinical trials published in high impact oncology journals found seeding trials account for 24.6% of publications. 37.1% of industry sponsored trials are seed studies. Seed studies are more common among the major disease sites or sites for which targeted therapies exist.

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