Combination of dabrafenib plus trametinib for BRAF and MEK inhibitor pretreated patients with advanced BRAFV600-mutant melanoma: an open-label, single arm, dual-centre, phase 2 clinical trial

2017 ◽  
Vol 18 (4) ◽  
pp. 464-472 ◽  
Author(s):  
Max Schreuer ◽  
Yanina Jansen ◽  
Simon Planken ◽  
Ines Chevolet ◽  
Teofila Seremet ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Mek Inhibitor ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Clinical Trial ◽  
Pretreated Patients

scholarly journals A Phase 2 Clinical Trial of Trametinib and Low-Dose Dabrafenib in Patients with Advanced Pretreated NRASQ61R/K/L Mutant Melanoma (TraMel-WT)

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2010
Author(s):  
Gil Awada ◽  
Julia Katharina Schwarze ◽  
Jens Tijtgat ◽  
Giuseppe Fasolino ◽  
Hendrik Everaert ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Low Dose ◽  
Objective Response ◽  
Braf Inhibitor ◽  
Skin Toxicity ◽  
Mek Inhibitor ◽  
Phase 2 ◽  
Cutaneous Toxicity ◽  
Full Dose ◽  
Phase 2 Clinical Trial

Background: MEK-inhibitor monotherapy has activity in advanced NRASQ61R/K/L mutant melanoma but is associated with dose-limiting cutaneous toxicity. The combination of a BRAF- with a MEK-inhibitor at their full dose (as in BRAFV600E/K mutant melanoma) has low cutaneous toxicity. It is unknown whether a low dose of BRAF-inhibitor can mitigate the skin toxicity associated with full-dose MEK-inhibitor treatment in patients with advanced NRASQ61R/K/L mutant melanoma. Methods: This two-stage phase 2 clinical trial investigated trametinib 2 mg once daily in patients with advanced NRASQ61R/K/L mutant melanoma who were pretreated with immune checkpoint inhibitors. In case of trametinib-related cutaneous toxicity, low-dose dabrafenib (50 mg twice daily) was added to prevent recurrent cutaneous toxicity (pre-amendment). Following an amendment, trametinib was combined upfront with low-dose dabrafenib (post-amendment). Objective response rate (ORR) served as the primary endpoint. Results: All 6 patients enrolled pre-amendment developed trametinib-related cutaneous toxicity, necessitating treatment interruption. Combining trametinib with low-dose dabrafenib prevented recurrent skin toxicity thereafter. Trametinib-related skin toxicity was effectively mitigated in all 10 patients post-amendment. In all 16 included patients, the ORR and disease control rate was 6.3% (1 partial response) and 50.0%, respectively. The trial was halted after the first stage. Conclusions: Combining full-dose trametinib with low-dose dabrafenib can mitigate MEK-inhibitor-related skin toxicity but was insufficiently active in this patient population. This combination can be of further interest for the treatment of MEK-inhibitor-sensitive tumors.

scholarly journals 988 An open-label phase 2 clinical trial of topical remetinostat gel for basal cell carcinoma

2019 ◽  
Vol 139 (5) ◽  
pp. S171
Author(s):  
N. Urman ◽  
S. Eichstadt ◽  
H. Do ◽  
A.N. Mirza ◽  
S. Li ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Basal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Basal Cell ◽  
Phase 2 ◽  
Open Label ◽  
Open Label Phase ◽  
Phase 2 Clinical Trial

Of mice and men: an open-label pilot study for treatment of immune thrombocytopenic purpura by an inhibitor of Syk

Blood ◽  
2009 ◽  
Vol 113 (14) ◽  
pp. 3154-3160 ◽  
Author(s):  
Anna Podolanczuk ◽  
Alan H. Lazarus ◽  
Andrew R. Crow ◽  
Elliot Grossbard ◽  
James B. Bussel
Keyword(s):  
Clinical Trial ◽  
Platelet Count ◽  
Immune Thrombocytopenic Purpura ◽  
Disease Models ◽  
Phase 2 ◽  
Open Label ◽  
Thrombocytopenic Purpura ◽  
Phase 2 Clinical Trial ◽  
Persistent Response ◽  
Refractory Itp

Abstract To determine whether inhibition of Syk would be useful in FcγR-dependent cytopenias such as immune thrombocytopenic purpura (ITP) or autoimmune hemolytic anemia, mouse models were used to evaluate efficacy of R406, an inhibitor of Syk function, in treating cytopenia. Both disease models responded favorably to treatment, with amelioration of ITP being more dramatic. Thus, phase 2 clinical trial was initiated to study the effects of Syk inhibition in humans with ITP. Sixteen adults with chronic ITP were entered into an open-label, single-arm cohort dose-escalation trial beginning with 75 mg and escalating as high as 175 mg twice daily. Doses were increased until a persistent response was seen, toxicity occurred, or 175 mg twice daily was reached. Eight patients achieved persistent responses with platelet counts greater than 50 × 109/L (50 000 mm3) on more than 67% (actually 95%) of their study visits, including 3 who had not persistently responded to thrombopoietic agents. Four others had nonsustained responses. Mean peak platelet count exceeded 100 × 109/L (100 000 mm3) in these 12 patients. Toxicity was primarily GI-related with diarrhea (urgency) and vomiting; 2 patients had transaminitis. In conclusion, inhibition of Syk was an efficacious means of increasing and maintaining the platelet count in half the patients with chronic refractory ITP. (ClinicalTrials.gov, no. NCT00706342).

Apatinib for advanced osteosarcoma after failure of standard multimodal therapy: An open label phase 2 clinical trial.

2018 ◽  
Vol 36 (15_suppl) ◽  
pp. 11520-11520 ◽  
Author(s):  
Lu Xie ◽  
Jie Xu ◽  
Xin Sun ◽  
Xiaodong Tang ◽  
Taiqiang Yan ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Multimodal Therapy ◽  
Phase 2 ◽  
Open Label ◽  
Open Label Phase ◽  
Phase 2 Clinical Trial

scholarly journals New chemotherapy regimens and biomarkers for Chagas disease: the rationale and design of the TESEO study, an open-label, randomised, prospective, phase-2 clinical trial in the Plurinational State of Bolivia

BMJ Open ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. e052897
Author(s):  
Cristina Alonso-Vega ◽  
Julio A Urbina ◽  
Sergi Sanz ◽  
María-Jesús Pinazo ◽  
Jimy José Pinto ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Chagas Disease ◽  
Treatment Phase ◽  
Standard Of Care ◽  
Ethics Committees ◽  
Pharmacokinetic Data ◽  
Phase 2 ◽  
Open Label ◽  
Phase 2 Clinical Trial ◽  
Prospective Phase

IntroductionChagas disease (CD) affects ~7 million people worldwide. Benznidazole (BZN) and nifurtimox (NFX) are the only approved drugs for CD chemotherapy. Although both drugs are highly effective in acute and paediatric infections, their efficacy in adults with chronic CD (CCD) is lower and variable. Moreover, the high incidence of adverse events (AEs) with both drugs has hampered their widespread use. Trials in CCD adults showed that quantitative PCR (qPCR) assays remain negative for 12 months after standard-of-care (SoC) BZN treatment in ~80% patients. BZN pharmacokinetic data and the nonsynchronous nature of the proliferative mammal-dwelling parasite stage suggested that a lower BZN/NFX dosing frequency, combined with standard or extended treatment duration, might have the same or better efficacy than either drug SoC, with fewer AEs.Methods and analysisNew ThErapies and Biomarkers for ChagaS infEctiOn (TESEO) is an open-label, randomised, prospective, phase-2 clinical trial, with six treatment arms (75 patients/arm, 450 patients). Primary objectives are to compare the safety and efficacy of two new proposed chemotherapy regimens of BZN and NFX in adults with CCD with the current SoC for BZN and NFX, evaluated by qPCR and biomarkers for 36 months posttreatment and correlated with CD conventional serology. Recruitment of patients was initiated on 18 December 2019 and on 20 May 2021, 450 patients (study goal) were randomised among the six treatment arms. The treatment phase was finalised on 18 August 2021. Secondary objectives include evaluation of population pharmacokinetics of both drugs in all treatment arms, the incidence of AEs, and parasite genotyping.Ethics and disseminationThe TESEO study was approved by the National Institutes of Health (NIH), U.S. Food and Drug Administration (FDA), federal regulatory agency of the Plurinational State of Bolivia and the Ethics Committees of the participating institutions. The results will be disseminated via publications in peer-reviewed journals, conferences and reports to the NIH, FDA and participating institutions.Trial registration numberNCT03981523.

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