Feasibility study of microbial ecosystem therapeutics (MET-4) to evaluate effects of fecal microbiome in patients on immunotherapy (MET4-IO).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. TPS2664-TPS2664
Author(s):  
Tira Jing Ying Tan ◽  
Marcus O. Butler ◽  
Aaron Richard Hansen ◽  
David Hogg ◽  
Adrian G. Sacher ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Solid Tumors ◽  
Alpha Diversity ◽  
Nucleic Acid Detection ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Shotgun Metagenomics ◽  
Fecal Microbiome ◽  
Significant Difference ◽  
Group B

TPS2664 Background: Differences in microbiome diversity and composition in immune checkpoint inhibitor (ICI)-responders vs non-responders have been demonstrated. Transplantation of responder feces in mouse models recapitulated the ICI-responsive phenotype. MET-4 is an oral alternative to fecal transplant consisting a well-defined mixture of intestinal bacteria isolated from healthy donor stool sample. We hypothesize that co-administration of MET-4 with ICI is safe and results in alterations of the gut microbiota. Methods: Three cohorts (n = 65) of subjects with any advanced solid tumor type treated with monotherapy anti- PD1/PD-L1 antibody outside of a therapeutic clinical trial will be enrolled. Group A: safety cohort of 5 subjects already on ICI will receive MET-4 in addition to standard of care (SOC) ICI. If < 2 subjects report adverse events of CTCAE grade ≥3 within 4 weeks at least possibly related to MET-4, this dose will be declared safe and groups B/C may start enrolling. Group B (n = 40): subjects with advanced solid tumors starting on ICI, randomized 3:1 to MET-4 plus SOC vs. SOC. Group C (n = 20): subjects with advanced solid tumors already on ICI with first unconfirmed disease progression randomized 1:1 to MET-4 plus ICI continuation vs. continuing ICI. Serial stool samples will be collected for taxonomic composition, diversity, metagenomics content and MET-4 species abundance. We anticipate the following analyses: 16S rRNA sequencing, shotgun metagenomics sequencing, qPCR, Nanostring nucleic acid detection and metabolomics profiling. Serial blood sampling for flow cytometry/CyTOF. Immune microenvironment of tumor specimen will be examined using immunohistochemistry. Other major inclusion criteria: willingness to provide correlative samples, RECIST v1.1 measurable disease and ECOG 0-2. Subjects unable to swallow oral medications are excluded. For the primary objective of cumulative relative abundance and changes of ICI-responsiveness associated species between baseline and day 12 MET-4, assuming a change of 0.5 standard deviation (SD) of microbial alpha diversity, our study will have ≥84% power to identify a significant difference given a significance level at 0.05 in group B. Assuming a change of 0.9 SD of microbial alpha diversity, we will have ≥83% power to identify a significant difference in group C. Response rates and progression free survival will be assessed per RECIST v1.1 and compared with historical data. Clinical trial information: NCT03686202.

Trial in progress: A phase 1-2 multicenter, open-label, dose-escalation and dose-expansion study to evaluate the safety, pharmacokinetics, pharmacodynamics, and antitumor activity of ABN401 in patients with advanced solid tumors.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS3157-TPS3157
Author(s):  
Dae Ho Lee ◽  
Aflah Roohullah ◽  
Byoung Chul Cho ◽  
Charlotte Rose Lemech ◽  
Paul L. de Souza ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Solid Tumors ◽  
Dose Escalation ◽  
Phase 1 ◽  
Locally Advanced ◽  
Local Therapy ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Phase 2 ◽  
Open Label

TPS3157 Background: c-MET (hepatocyte growth factor (HGF) receptor) overexpression, either by gene amplification, or mutation is associated with oncogenic transformation in numerous malignancies including lung, gastric, skin, renal, colorectal, and pancreatic cancers. ABN401 inhibits the activation of c-MET by reversibly interfering with the binding of c-Met tyrosine kinase to adenosine triphosphate (ATP) and blocking the receptor's downstream signaling that has demonstrated efficacy in NSCLC and gastric cancer in mouse xenograft and PDx models. This clinical trial is in progress in patients with advanced cancers. Methods: ABN401 is being evaluated in an open-label, non-randomized, dose-escalation (phase 1) study in patients with advanced solid tumors, and dose-expansion (phase 2) in patients with targeted indications and c-MET biomarker expression (NCT04052971). The phase 1 explores ascending daily doses of oral ABN401 monotherapy in 21-day cycles to identify the maximum tolerated dose (MTD) and recommended Phase 2 dose (RP2D). A preplanned extension (pilot expansion) study has been initiated based on predefined positive efficacy signals at intermediate doses up to 10 NSCLC patients who have c-MET alteration. Once RP2D is determined, the phase 2 expansion of up to 10-29 patients in four specific tumor-type cohorts is planned, utilizing a Simon's optimal two-stage design to evaluate the clinical activity of ABN401. ABN401-001 study began enrolling patients in August 2019 and is ongoing in Korean and Australia. Dose escalation up to cohort 4 has been completed, enrollment to cohort 5 began in November 2020. AEs are assessed according to CTCAE v5. Tumor response is determined according to RECIST 1.1 criteria and safety findings reviewed by the DRC, which will determine the RP2D and MTD. Key Phase 1 eligibility criteria include 1) histological or cytological diagnosis of melanoma or any type of carcinoma or sarcoma and 2) refractory metastatic disease, or refractory locally advanced disease not amenable to local therapy. For the extension (pilot expansion) study, patients must have NSCLC with MET exon 14 skipping, MET amplification and/or c-MET overexpression. An exploratory study is being conducted for co-development of a companion diagnostic (CDx) system including a CTC device and ddPCR kit through liquid biopsy. Clinical trial information: NCT04052971.

Suboptimal clinician awareness of appropriate NTRK fusion testing and TRK inhibitor use in solid tumors.

2021 ◽  
Vol 39 (28_suppl) ◽  
pp. 229-229
Author(s):  
Ryan P. Topping ◽  
Krista Marcello ◽  
Terrence Fagan ◽  
Timothy A. Quill ◽  
Todd Michael Bauer ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Progressive Disease ◽  
Inhibitor Therapy ◽  
Tumor Type ◽  
Advanced Solid Tumors ◽  
Educational Activities ◽  
Time Period ◽  
Trk Inhibitors ◽  
Therapeutic Alternatives ◽  
Selection Of

229 Background: Since late 2018, 2 TRK inhibitors—larotrectinib and entrectinib—have been approved by the EMA and FDA for treating patients with advanced solid tumors harboring an NTRK fusion and progressive disease or no therapeutic alternatives. It is recommended that testing for NTRK fusions occur as early as possible after a diagnosis of advanced disease in patients with solid tumors to inform potential use of TRK inhibitors. Methods: Between April 2018 and April 2021, we conducted multiple live and online educational activities for oncology healthcare professionals (HCPs) on NTRK fusion testing and/or TRK inhibitor treatment for varied solid tumors. Each activity included polling questions designed to assess HCP knowledge and practice patterns. In this analysis, we assessed HCP responses to these questions to evaluate awareness of expert recommendations on NTRK fusion testing and the selection of TRK inhibitor therapy for appropriate patients. Results: In 6 live and online activities with data from April 2018 to April 2021, 29% of HCPs (n = 844) indicated that they ordered molecular profiling to test for NTRK fusions in all solid tumors in their current practice. Of note, low rates of testing were reported in TRK inhibitor/ NTRK testing-focused activities throughout this time period, with no significant increase over time. In assessing different patient cases across 8 activities where experts recommended TRK inhibitor therapy as optimal, many HCPs did not select a TRK inhibitor, with considerable variance by tumor type (Table). *For all cases, experts selected larotrectinib and/or entrectinib as optimal treatment. †HCP respondents. GBM, glioblastoma; GI, gastrointestinal; MSI-H, microsatellite instability-high; PD, progressive disease; PTC, papillary thyroid cancer.Conclusions: The rate of broad testing for NTRK fusions across patients with solid tumors remains low, and many HCPs lack awareness of when to consider a TRK inhibitor. Educational activities designed to address these deficiencies would be of clear benefit to HCPs treating patients with advanced solid tumors. A detailed analysis of HCP trends will be presented.[Table: see text]

Esthetic and Clinical Performance of Implant-Supported All-Ceramic Crowns Made with Prefabricated or CAD/CAM Zirconia Abutments: A Randomized, Multicenter Clinical Trial

2016 ◽  
Vol 96 (2) ◽  
pp. 163-170 ◽  
Author(s):  
J.G. Wittneben ◽  
J. Gavric ◽  
U.C. Belser ◽  
M.M. Bornstein ◽  
T. Joda ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Performance ◽  
Multicenter Clinical Trial ◽  
Anterior Maxilla ◽  
Single Crown ◽  
Significant Difference ◽  
All Ceramic ◽  
Cad Cam ◽  
Group A ◽  
Group B

Patients’ esthetic expectations are increasing, and the options of the prosthetic pathways are currently evolving. The objective of this randomized multicenter clinical trial was to assess and compare the esthetic outcome and clinical performance of anterior maxillary all-ceramic implant crowns (ICs) based either on prefabricated zirconia abutments veneered with pressed ceramics or on CAD/CAM zirconia abutments veneered with hand buildup technique. The null hypothesis was that there is no statistically significant difference between the 2 groups. Forty implants were inserted in sites 14 to 24 (FDI) in 40 patients in 2 centers, the Universities of Bern and Geneva, Switzerland. After final impression, 20 patients were randomized into group A, restored with a 1-piece screw-retained single crown made of a prefabricated zirconia abutment with pressed ceramic as the veneering material using the cut-back technique, or group B using an individualized CAD/CAM zirconia abutment (CARES abutment; Institut Straumann AG) with a hand buildup technique. At baseline, 6 mo, and 1 y clinical, esthetic and radiographic parameters were assessed. Group A exhibited 1 dropout patient and 1 failure, resulting in a survival rate of 94.7% after 1 y, in comparison to 100% for group B. No other complications occurred. Clinical parameters presented stable and healthy peri-implant soft tissues. Overall, no or only minimal crestal bone changes were observed with a mean DIB (distance from the implant shoulder to the first bone-to-implant contact) of −0.15 mm (group A) and 0.12 mm (group B) at 1 y. There were no significant differences at baseline, 6 mo, and 1 y for DIB values between the 2 groups. Pink esthetic score (PES) and white esthetic score (WES) values at all 3 examinations indicated stability over time for both groups and pleasing esthetic outcomes. Both implant-supported prosthetic pathways represent a valuable treatment option for the restoration of single ICs in the anterior maxilla ( ClinicalTrials.gov NCT02905838).

Comparing the effectiveness of mulligan mobilization versus cyriax approach in the management of patients with subacute lateral epicondylitis

2020 ◽  
pp. 1-11
Author(s):  
Aqeel Ahmed ◽  
Muhammad Ibrar ◽  
Aatik Arsh ◽  
Sonia Wali ◽  
Shoukat Hayat ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Functional Disability ◽  
Tennis Elbow ◽  
Lateral Epicondylitis ◽  
Evaluation Index ◽  
Pain Subscale ◽  
Significant Difference ◽  
Group A ◽  
Physical Tests ◽  
Group B

Abstract Objective: To determine the effectiveness of Mulligan mobilisation versus Cyriax approach in the management of patients with subacute lateral epicondylitis. Methods: The clinical trial was conducted at the District Headquarter Hospital, Bahawalnagar, Pakistan, from September to December 2018, and comprised lateral epicondylitis patients having symptoms for >2 weeks. The diagnosis was confirmed on the basis of physical tests and musculoskeletal ultrasound. The subjects were randomly allocated to two equal groups A and B. Group A received deep transverse friction and Mill’s manipulation according to Cyriax approach, while group B received Mulligan mobilisation with movement techniques. Patient-related tennis elbow evaluation index was used to collect data which was analysed using SPSS 20. Results: Of the 60 patients, there were 30(50%) in each of the two groups. The overall mean age was 35.27±7.30 years, and 38(63.3%) participants were male.  After 4 weeks of treatment sessions, both groups showed significant improvements (p<0.05) in pain and functional disability scores. Group A showed significantly more improvement (p<0.05) in pain subscale scores compared to group B, while group B showed significant improvement (p<0.05) in functional disability subscale scores compared to group A. There was no significant difference (p>0.05) between the groups on total the patient-related tennis elbow evaluation index score. Conclusion: Both Mulligan mobilisation with movement and Cyriax approach decreased pain and improved functional status in lateral epicondylitis patients. Key Words: Elbow, Lateral epicondylitis, Massage, Mobilisation, Physiotherapy. Continuous..,

Dose finding study of the combination of satraplatin and gemcitabine in patients with advanced solid tumors

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e13534-e13534
Author(s):  
E. Donato Di Paola ◽  
S. Alonso ◽  
A. D’Alessio ◽  
R. Giuliani ◽  
F. Calabrò ◽  
...  
Keyword(s):  
Solid Tumors ◽  
Unknown Origin ◽  
Dose Finding ◽  
Advanced Solid Tumors ◽  
Prior Chemotherapy ◽  
Starting Dose ◽  
Finding Study ◽  
Group A ◽  
Level 1 ◽  
Group B

e13534 Background: The potential advantage of combining satraplatin (S) a novel oral platinum with Gem is attractive. MTD and DLT of combination S and Gem in patients (pts) with advanced solid tumors was evaluated. Methods: Cohorts of 3–6 pts (modified Fibonacci) received escalating doses of i.v. Gem on days (d) 1, 8 and 15 Q 28 d followed by oral S on d 1–5. Seventeen pts with metastatic solid tumors were separated into 2 groups: A) Pts that had progressed following cytotoxic therapy and B) Pts who had received no prior chemotherapy. Starting dose was Gem 800 mg in both groups, S 40 mg and 60 mg for A and B respectively. Results: Group A. 6 previously treated pts with 1 or 2 regimens (3 prostate, 1 hepatocarcinoma, 1 bladder and 1 thymic ca) received 25 cycles, median 2 (2–12). 2 DLTs (G3 transaminases) were observed in 6 pts treated at level 1. Other G3 major toxicities were: thrombocytopenia (1 pt) and diarrhea (1 pt). 2 pts had PSA declines, with TTP of 630 days in 1 of them. Group B. 11 pts with no prior chemotherapy (4 hepatocarcinoma, 4 pancreas, 1 renal, 1 unknown origin and 1 gallbladder), received 38 cycles, median 2 (1–12). 1 DLT (G3 diarrhea) was observed in 8 pts treated at level 1 (2 not evaluable; received Gem d1 only), DLT (G3 thrombocytopenia) was observed in 3 pts treated at level 2 (Gem 1000, S 60). Other G3 toxicities were: thrombocytopenia (3 pts) and neutropenia (3 pts). 1 CR (pancreas) and 1 PR (gallbladder) were observed. Gem d8 or d15 was omitted in 11 of 17 pts during the 1st cycle. Conclusions: In this study the combination of S and Gem showed a clinically acceptable toxicity profile with promising antitumor activity. However, since in cycle 1, it was not possible to administer Gem on both d8 and d15 on 11 occasions, a 2nd study was initiated with S d1–3 and Gem d1 and 8 given on a Q 21 d schedule. Sponsored by GPC Biotech No significant financial relationships to disclose.

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