Microfluidic Liquid-Liquid Extraction Chip with Integrated Raman Sensors Phase I and Phase II Final Report

2021 ◽  
Author(s):  
Christina Gasbarro
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Liquid Extraction ◽  
Final Report ◽  
Liquid Liquid Extraction

First and final report of a phase II study of the poly(ADP-ribose) polymerase (PARP) inhibitor, AG014699, in combination with temozolomide (TMZ) in patients with metastatic malignant melanoma (MM)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 8013-8013 ◽  
Author(s):  
R. Plummer ◽  
P. Lorigan ◽  
J. Evans ◽  
N. Steven ◽  
M. Middleton ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Phase I Study ◽  
Phase Ii Study ◽  
Excision Repair ◽  
Early Stage ◽  
Single Agent ◽  
Error Rates ◽  
Parp Inhibition ◽  
Final Report

8013 Background: Inhibition of PARP and thus Base Excision Repair has been shown to potentiate the cytotoxicity of DNA damaging agents preclinically. A Phase I study of AG014699 + TMZ reported at ASCO 2005 showed that a full dose of TMZ could be given in the presence of profound PARP inhibition. We report the results of a Phase II study of AG014699 12 mg/m2 and TMZ 200 mg/m2 5x daily q 4 weekly in patients with advanced MM. This Phase II study commenced in March 2005 and completed recruitment in December 2005. Methods: Patients with measurable MM who were chemotherapy naïve, performance status ≤ 2, and had standard blood indices for early trials were recruited. Patients with ocular melanoma or brain metastases were excluded. Treatment was given until progression, with repeat imaging every 2 cycles. A two stage phase II design was used, with the hypothesis to be tested that the response rate to TMZ would be increased to 25%. α and β error rates were set at 0.10. 27 patients were recruited into the first stage with continuation to 40 patients if ≥3 partial responses were observed. Results 40 patients who fulfilled the eligibility criteria were recruited and treated. The required 3 responses were seen at an early stage. More enhancement of TMZ associated myelosuppression by the addition of AG014699 has been observed compared to the phase I study (Grade 4 thrombocytopenia 12% cycles, grade 4 neutropenia 15% to date). There has been one toxic death in cycle 1 (febrile neutropenia), 3 further patients hospitalised with myelosuppression and 12 patients in total requiring dose reduction of TMZ to 150 mg/m2 (1 to 100 mg/m2). All of these patients continued treatment at the reduced dose. Other toxicities have been fatigue and mild nausea. Currently there are 4 confirmed partial responses, 4 prolonged disease stabilisations and 20 patients are too early to evaluate. Conclusions The combination of TMZ and AG014666 shows encouraging activity in MM. Myelosuppression is greater than would be expected with single agent TMZ. PARP expression and activity in blood cells and tumour will be correlated with the mature outcome data from the trial. [Table: see text]

scholarly journals Microgrid Design, Development and Demonstration - Final Report for Phase I and Phase II

2011 ◽  
Author(s):  
Sumit Bose ◽  
Michael Krok
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Final Report ◽  
Design Development ◽  
Microgrid Design

Final report of a phase I/II study of veliparib (Vel) in combination with 5-FU and oxaliplatin (FOLFOX) in patients (pts) with metastatic pancreatic cancer (mPDAC).

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 4015-4015 ◽  
Author(s):  
Michael J. Pishvaian ◽  
Hongkun Wang ◽  
Sarah Parenti ◽  
Aiwu Ruth He ◽  
Jimmy J. Hwang ◽  
...  
Keyword(s):  
Phase I ◽  
Phase Ii ◽  
Parp Inhibitor ◽  
Objective Response ◽  
Progression Free Survival ◽  
Primary Objective ◽  
Final Report ◽  
Cancer Syndrome ◽  
Previously Treated ◽  
Ecog Ps

4015 Background: 17 – 25% of mPDACs harbor DNA damage response (DDR) mutations, the presence of which can be predictive of a response to platinum and PARP inhibitor-based therapy. The PARP inhibitor, Vel is a potent sensitizing agent for, and has been safely combined with DNA-damaging chemotherapies. Methods: We initiated a Phase I/II trial of Vel + FOLFOX in pts with mPDAC. Pts received standard mFOLFOX6 except without the 5FU bolus, Q2 weeks. For the Phase I portion, a 3+3 dose escalation of Vel identified a recommended Phase II dose of 200mg orally BID, days 1-7, Q2 weeks. For the Phase II portion, we enrolled two cohorts: 1) Untreated pts; 2) Previously treated pts. Also, for Phase II, pts were pre-selected if they had either a pathogenic germline or somatic DDR mutation (e.g. BRCA1/2, PALB2, ATM), and/or a family history suggestive of a breast or ovarian cancer syndrome (labelled FH+). Objective response rate (ORR) was the primary objective of the Phase II cohorts; key secondary endpoints were median progression-free survival (PFS) and overall survival (OS). Results: Between 01-2011 and 12-2018, 64 pts received treatment, 31 in Phase I, and 15 untreated and 18 previously treated in Phase II. The combination was well tolerated, with the main Grade 3/4 AEs being myelosuppression (16%) and nausea/vomiting (6%). Of the 64 pts, 55% were male; median age was 64; 95% had an ECOG PS of 1; 78% were platinum-naïve; 69% were FH+; and 27% had a known DDR mutation. 57 pts were evaluable for response, and the ORR, PFS, and OS for the different pt subgroups are detailed below. The Phase II cohorts achieved the primary endpoint of an ORR ≥ 25%. Most notably, plat-naïve, FH+, and DDR mutation+ pts had an ORR of 58%. Conclusions: The combination of Vel + FOLFOX is safe, well tolerated, and shows promising efficacy particularly in plat-naïve pts who are FH+ and/or harbor DDR mutations. A randomized trial to assess the contribution of Vel to the regimen is warranted. Clinical trial information: NCT01489865. [Table: see text]

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