scholarly journals Ledipasvir/sofosbuvir with or without ribavirin for 8 or 12 weeks for the treatment of HCV genotype 4 infection: results from a randomised phase III study in Egypt

Gut ◽  
2018 ◽  
Vol 68 (4) ◽  
pp. 721-728 ◽  
Author(s):  
Gamal Shiha ◽  
Gamal Esmat ◽  
Mohamed Hassany ◽  
Reham Soliman ◽  
Mohamed Elbasiony ◽  
...  
Keyword(s):  
Previous Treatment ◽  
Phase Iii ◽  
Open Label ◽  
Genotype 4 ◽  
Hcv Genotype ◽  
Multicentre Phase ◽  
Highly Effective ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
To Receive

ObjectiveWe evaluated the efficacy and safety of ledipasvir/sofosbuvir alone and with ribavirin for 8 and 12 weeks in Egyptian patients with and without cirrhosis, who were infected with hepatitis C virus (HCV) genotype 4, including those who had failed previous treatment with sofosbuvir regimens.DesignIn this open-label, multicentre, phase III study, treatment-naive patients were randomised to receive 8 or 12 weeks of ledipasvir/sofosbuvir±ribavirin. Interferon treatment-experienced patients were randomised to receive 12 weeks of ledipasvir/sofosbuvir±ribavirin, while sofosbuvir-experienced or ledipasvir/sofosbuvir-experienced patients received 12 weeks of ledipasvir/sofosbuvir+ribavirin. Randomisation was stratified by cirrhosis status. The primary endpoint was sustained virological response 12 weeks post-treatment (SVR12).ResultsWe enrolled 255 patients from four centres in Egypt. Among treatment-naive patients, SVR12 rates were 95% and 90% for those receiving 8 weeks of ledipasvir/sofosbuvir alone and with ribavirin, respectively, and 98% for those receiving 12 weeks of ledipasvir/sofosbuvir both alone and with ribavirin. Among interferon-experienced patients, SVR rates were 94% for those receiving 12 weeks of ledipasvir/sofosbuvir and 100% for those receiving 12 weeks of ledipasvir/sofosbuvir plus ribavirin. All patients previously treated with sofosbuvir regimens who received ledipasvir/sofosbuvir plus ribavirin achieved SVR12. The most common adverse events, headache and fatigue, were more common among patients receiving ribavirin.ConclusionAmong non-cirrhotic treatment-naive patients with HCV genotype 4, 8 weeks of ledipasvir/sofosbuvir±ribavirin was highly effective. Twelve weeks of ledipasvir/sofosbuvir±ribavirin was highly effective regardless of presence of cirrhosis or prior treatment experience, including previous treatment with sofosbuvir or ledipasvir/sofosbuvir.Trial registration numberNCT02487030.

scholarly journals TRIPLETE: a randomised phase III study of modified FOLFOXIRI plus panitumumab versus mFOLFOX6 plus panitumumab as initial therapy for patients with unresectableRASandBRAFwild-type metastatic colorectal cancer

ESMO Open ◽  
2018 ◽  
Vol 3 (4) ◽  
pp. e000403 ◽  
Author(s):  
Beatrice Borelli ◽  
Roberto Moretto ◽  
Sara Lonardi ◽  
Andrea Bonetti ◽  
Carlotta Antoniotti ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Metastatic Colorectal Cancer ◽  
Initial Therapy ◽  
Phase Iii ◽  
Wild Type ◽  
Open Label ◽  
Multicentre Phase ◽  
Phase Iii Study ◽  
Colorectal Cancer Patients ◽  
To Receive

BackgroundFOLFOXIRI plus bevacizumab is considered a standard option in the upfront treatment of clinically selected patients with metastatic colorectal cancer irrespective ofRASandBRAFmolecular status. The randomised MACBETH and VOLFI studies showed that a modified FOLFOXIRI regimen in combination with cetuximab or panitumumab, respectively, achieved high therapeutic activity inRASandBRAFwild-type patients with an acceptable toxicity profile. Drawing from these considerations, we designed TRIPLETE study aiming at comparing two different chemotherapy backbones (mFOLFOXIRI or mFOLFOX6) in combination with panitumumab in the first-line treatment of patients withRASandBRAFwild-type metastatic colorectal cancer.MethodsThis is a prospective, open-label, multicentre phase III trial in which initially unresectable and previously untreatedRASandBRAFwild-type metastatic colorectal cancer patients are randomised to receive a standard treatment with mFOLFOX6 plus panitumumab or an experimental regimen with modified FOLFOXIRI (irinotecan 150 mg/m2, oxaliplatin 85 mg/m2, L-leucovorin 200 mg/m2, 5-fluoruracil 2400 mg/m248-hour continuous infusion) plus panitumumab up to 12 cycles, followed by panitumumab plus 5-fluorouracil and L-leucovorin until disease progression. The primary endpoint is overall response rate according to RECIST 1.1 criteria.DiscussionThe relative benefit of chemotherapy intensification when using an anti-EGFR-based regimen in molecularly selected patients is unknown; TRIPLETE study aims at filling this gap of knowledge. The study is sponsored by the Gruppo Oncologico Nord Ovest Cooperative Group and is currently ongoing at 42 Italian centres.Clinical trial informationNCT03231722.

Randomized, multicenter, open-label, phase III study of the BTK inhibitor ibrutinib versus chlorambucil in patients 65 years or older with treatment-naive CLL/SLL (RESONATE-2, PCYC-1115-CA).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS7130-TPS7130 ◽  
Author(s):  
Jan Andreas Burger ◽  
Paolo Ghia ◽  
Aaron Polliack ◽  
Constantine Tam ◽  
Deepali Suri ◽  
...  
Keyword(s):  
Performance Status ◽  
Single Agent ◽  
Unmet Need ◽  
Previous Treatment ◽  
Phase Iii ◽  
Open Label ◽  
Ecog Performance Status ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Ecog Ps

TPS7130 Background: There is an unmet need for safer and more effective therapies for CLL patients who are older/have comorbidites. Ibrutinib, a small molecule inhibitor of BTK, has demonstrated single-agent activity in CLL in the Ph 1b/2 study, PCYC-1102-CA. Treatment-naïve (TN) patients aged >= 65 yrs (n=31) experienced an estimated PFS and OS of 96% at 26 months; ORRs per iwCLL were: 10% CR, 58% PR, and 13% PR with lymphocytosis (Byrd, ASH 2012). AEs were generally Grade 1/2, most commonly diarrhea. Incidence of Grade 3/4 hematologic toxicities was low. These findings support a phase III study of ibrutinib in older patients with treatment-naïve CLL/SLL. Methods: The ongoing study is a randomized, multicenter, open label Ph 3 study comparing safety and efficacy of ibrutinib vs. chlorambucil in TN patients aged >= 65 yrs with CLL/SLL. Approximately 272 patients will be randomized in 1:1 ratio to receive either chlorambucil or ibrutinib, stratified for ECOG PS and Rai stage. Oral chlorambucil will be administered at 0.5 mg/kg on Days 1 and 15 of each 28-day cycle, for up to 12 cycles. Ibrutinib 420 mg q.d. will continue until PD or unacceptable toxicity. Key incl. criteria include age >= 65 yrs, active disease requiring treatment per iwCLL, measurable nodal disease by CT, ECOG performance status 0-2, and adequate organ function (ANC ≥1,000/μL, platelets ≥50,000/μL, creatinine clearance ≥30 mL/min). Key excl. criteria include Richter’s transformation, del(17p13.1) or previous treatment for CLL/SLL. The primary endpoint of the study is PFS, assessed by Independent Review Committee (IRC). Secondary endpoints include ORR, MRD-negative CRs, fatigue by FACIT-F, hematological improvement, safety, and tolerability. Subjects who relapse on PCYC-1115 will be enrolled on PCYC-1116 for long term follow up. Second line therapy is investigator choice; ibrutinib will be made available for patients who experience IRC-confirmed PD ≤12 months of completing chlorambucil therapy, if they meet the treatment criteria. Approximately 85 sites will enroll patients in North America, Europe, Israel, Australia/New Zealand and China. Enrollment began in Q1 2013. Clinical trial information: NCT01722487.

A single-arm, open-label, U.S. expanded access study of vemurafenib in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 8567-8567
Author(s):  
Lynn Mara Schuchter ◽  
Lawrence E. Flaherty ◽  
Omid Hamid ◽  
Gerald P. Linette ◽  
Sigrun Hallmeyer ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Response Rate ◽  
Phase Iii ◽  
Open Label ◽  
Expanded Access ◽  
Treatment Naïve ◽  
Phase Iii Study ◽  
Prior Systemic Therapy ◽  
Ecog Ps

8567 Background: Vemurafenib (vem) has been FDA approved for the treatment of unresectable or metastatic BRAFV600E mutated melanoma since August 2011 based on results of a randomized phase III study (treatment-naive) and a single arm phase II study (previously treated). We report results of an expanded access study that allowed appropriate patients (pts) to receive vem until the drug was approved. Methods: Eligible pts had metastatic melanoma with a BRAFV600E mutation as detected by the cobas 4800 BRAFV600 Mutation Test. Enrolled pts received oral vem 960 mg b.i.d. Adverse events (AEs) were evaluated for vem-related toxicities; tumor responses were assessed using RECIST 1.1. Results: 29 US sites screened 745 pts and enrolled 374 from December 2010 until October 2011. The following results are based on a median follow up time and treatment duration of 2 months. At baseline, mean age of pts was 54 y with 22% of pts ≥65 y; 75% had stage M1c disease; 29% had received radiotherapy for brain metastases. 19% of pts were ECOG PS 2 or 3; 71% of pts had prior systemic therapy for metastatic melanoma (21% 1 regimen; 50% ≥2 regimens). 50 pts had prior adjuvant treatment. At data cut-off, 243 pts had sufficient follow-up time for tumor assessment. In this group, the unconfirmed overall response rate was 52% (95% CI, 46 to 59). The median time to response was 1.8 months. Based on 240 pts with available ECOG PS status at time of analysis, response rate was 53% for pts with ECOG PS 0 or 1 (n=209), and 45% for pts with ECOG PS 2 or 3 (n=31). 370 pts were evaluable for safety analysis. The most common vem-related AEs were rash (36%), arthralgia (33%) and fatigue (21%) with the majority (~90%) of grade 1 or 2. 25 vem-related serious AEs were reported in 5.4% of pts with a slightly higher rate of pts with ECOG PS 2 or 3 (8.7%) compared to ECOG PS 0 or 1 (4.7%). 18% of pts missed at least one dose and 11% of pts required dose reduction of at least one level due to AEs. Conclusions: This expanded access study, with its limited follow-up time, confirms the established rapid and high tumor response rate with vem. No new safety signals were detected. Compared to the overall population, pts with an ECOG PS 2 or 3 demonstrated a similar benefit.

scholarly journals Novel combined single dose anti-hepatitis C therapy: a pilot study

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Gamal Shiha ◽  
Reham Soliman ◽  
Mohamed Elbasiony ◽  
Noureldien H. E. Darwish ◽  
Shaker A. Mousa
Keyword(s):  
Viral Load ◽  
Hepatitis C ◽  
Virologic Response ◽  
Fixed Dose ◽  
The Novel ◽  
Open Label ◽  
Genotype 4 ◽  
Treatment Regimens ◽  
Treatment Naïve ◽  
To Receive

AbstractThe new anti-hepatitis C virus (HCV) molecules improve treatment regimens and outcomes, but there are drawbacks. New combinations should target the HCV infectious cycle and be effective against all HCV genotypes. We developed the novel formulation Catvira, composed of epigallocatechingallate (EGCG) + sofosbuvir + ribavirin. Here, we compared Catvira to sofosbuvir + ribavirin tablets in patients with CHC genotype 4 in a randomized open-label efficacy and safety study. Treatment-naïve and treatment-experienced patients (n = 80) were randomly assigned to receive a single daily fixed dose of Catvira or sofosbuvir + ribavirin for 12 or 24 weeks. Both Catvira and sofosbuvir + ribavirin yielded similar outcomes of viral load (p < 0.001). Patients receiving Catvira had a significantly more rapid rate of viral load decline with sustained virologic response (SVR12) achieved by 90% of patients receiving 12 weeks of treatment. Catvira did not impact hemoglobin levels while sofosbuvir + ribavirin showed significant decline in hemoglobin levels after 24 weeks (p < 0.05). In this clinical trial (ClinicalTrials.gov Identifier NCT02483156), we found that Catvira administered daily for 12 or 24 weeks is safe, effective, and well-tolerated in both naïve and treatment-experienced patients with HCV genotype 4.

Efficacy and safety of BCD-017, a novel pegylated filgrastim: Results of open-label controlled phase II study in patients with breast cancer receiving myelosuppressive chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e20593-e20593 ◽  
Author(s):  
Olga V. Salafet ◽  
Tatiana V. Chernovskaya ◽  
Ludmila P. Sheveleva ◽  
Andrey V. Khorinko ◽  
Tatiana I. Prokopenko ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Phase Iii ◽  
Severe Neutropenia ◽  
Comparable Efficacy ◽  
Efficacy And Safety ◽  
Open Label ◽  
Group A ◽  
Phase Iii Study ◽  
Study Support ◽  
To Receive

e20593 Background: Pegfilgrastim (conjugate of filgrastim and 20 kDa polyethylene glycol (PEG) is approved for treatment of chemotherapy-associated neutropenia. BCD-017 (empegfilgrastim) is a covalent conjugate of filgrastim with 30 kDa PEG. Increased molecular weight of PEG molecule may provide additional benefits compared to pegfilgrastim. Methods: To compare efficacy and safety of filgrastim and BCD-017 at 3 mg and 6 mg doses an open-label, randomized, active-comparator, non-inferiority trial was conducted. 60 patients with histologically or cytologically confirmed breast cancer were randomly assigned to receive either subcutaneous (s.c.) injection of 3 mg BCD-017 (n=21), 6 mg BCD-017 (n = 20), or 5 mg/kg s.c. injections of filgrastim (n=19) administered daily until ANC ≥ 10x109 cells/L (maximum of 14 days) after chemotherapy (doxorubicin 60 mg/m2 and docetaxel 75 mg/m2) with stratification for weight and prior chemotherapy exposure. The primary efficacy endpoint was the incidence of severe neutropenia (ANC < 1.0x109 cells/L) during the first cycle of chemotherapy. Results: Incidence of severe neutropenia during the first chemotherapy cycle was 85,7%, 65,0% and 61,1% in BCD-017 3 mg, BCD-017 6 mg and filgrastim groups, respectively. Differences between BCD-017 groups and filgrastim group were not significant. Mean duration of grade 4 neutropenia in cycle 1 was 0,43, 0,40 and 0,33 days, accordingly (95% CI for difference between BCD-017 3 mg and filgrastim groups -0.22 to 0.41; 95% CI for difference between BCD-017 6 mg and filgrastim groups -0.25 to 0.38). Febrile neutropenia was observed only in BCD-017 3 mg and BCD-017 6 mg groups (one case in each group). A single administration of BCD-017 at the doses of 3 mg and 6 mg was as safe and well tolerated as standard daily filgrastim administration. There were no unexpected adverse events in all groups. Conclusions: The results of this study support comparable efficacy of single s.c. injection of 6 mg BCD-017 versus daily 5 mg/kg s.c. injections of filgrastim. Further phase III study of BCD-017 for treatment and prophylaxis of neutropenia in patients receiving chemotherapy is necessary. Clinical trial information: NCT01569087.

IMmotion151: A Randomized Phase III Study of Atezolizumab Plus Bevacizumab vs Sunitinib in Untreated Metastatic Renal Cell Carcinoma (mRCC)

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 578-578 ◽  
Author(s):  
Robert J. Motzer ◽  
Thomas Powles ◽  
Michael B. Atkins ◽  
Bernard Escudier ◽  
David F. McDermott ◽  
...  
Keyword(s):  
Progression Free Survival ◽  
Phase Iii ◽  
Anti Vegf ◽  
Treatment Naïve ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Intent To Treat ◽  
The Individual ◽  
To Receive

578 Background: Atezolizumab (atezo; anti–PD-L1) + bevacizumab (bev; anti-VEGF) showed first-line (1L) anti-tumor activity with a manageable safety profile in PD-L1+ mRCC pts in a Phase II study (McDermott ASCO-GU 2017). Here we describe the first randomized Phase III trial of a PD-L1/PD-1 pathway inhibitor combined with an anti-VEGF agent in 1L mRCC. Methods: IMmotion151 (NCT02420821) enrolled treatment-naïve pts regardless of prognostic risk group randomized 1:1 to receive atezo 1200 mg IV q3w + bev 15 mg/kg IV q3w or sunitinib (sun) 50 mg PO QD 4 wk on/2 wk off. Pts were stratified by PD-L1 status (< 1% vs ≥ 1% PD-L1 expression on tumor-infiltrating immune cells [IC]; SP142 IHC assay). Coprimary endpoints: progression-free survival (PFS; by investigator per RECIST v1.1) in PD-L1+ pts (≥ 1% IC) and overall survival (OS) in intent-to-treat (ITT) pts. Secondary endpoints included PFS in ITT pts, ORR and DOR. Results: Baseline characteristics were comparable between arms within PD-L1+ (40% of ITT) and ITT pts. Median survival follow-up was 15 mo. PFS HR for atezo + bev vs sun was 0.74 (95% CI 0.57, 0.96) in PD-L1+ pts and 0.83 (95% CI 0.70, 0.97) in ITT pts. OS was immature at first interim analysis. PFS benefit was consistent across analyzed subgroups, including MSKCC risk, liver metastases and sarcomatoid histology. In PD-L1+ pts, ORR was 43% and DOR was not reached for atezo + bev vs 35% and 12.9 mo for sun. 40% of atezo + bev–treated pts and 54% of sun-treated pts had treatment-related Gr 3-4 AEs; 12% and 8% of treatment-related all-Gr AEs led to discontinuation, respectively. Conclusions: The study showed longer PFS for atezo + bev vs sun in PD-L1+ pts. Improved PFS was also observed in ITT pts. Safety was consistent with that of the individual agents. These results support the use of atezo + bev as a 1L treatment option in mRCC. Clinical trial information: NCT02420821. [Table: see text]

RESPONSE: A randomized, open-label, phase III study of ruxolitinib in polycythemia vera (PV) patients resistant to or intolerant of hydroxyurea (HU).

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. TPS6643-TPS6643
Author(s):  
Srdan Verstovsek ◽  
Jean-Jacques Kiladjian ◽  
Victor Sandor ◽  
Jacek Lukawy ◽  
Jingjin Li ◽  
...  
Keyword(s):  
Myeloid Leukemia ◽  
Myeloproliferative Neoplasm ◽  
Phase Iii ◽  
Open Label ◽  
Phase 3 ◽  
Phase 2 Study ◽  
Open Label Phase ◽  
Clinical Responses ◽  
Phase Iii Study ◽  
To Receive

TPS6643^ Background: PV is a myeloproliferative neoplasm characterized by clonal stem cell proliferation, significant morbidity, shortened life span and possible evolution to myelofibrosis and acute myeloid leukemia. Splenomegaly, debilitating constitutional symptoms, and frequent phlebotomy requirements are common in advanced disease. HU, an established first-line agent for cytoreduction, can be associated with cytopenias, aphthous and leg ulcers, and other side effects. Control of hematocrit is not always achieved with HU, and many patients are either intolerant of or become resistant to HU. JAK2 plays a key role in the pathophysiology of PV; nearly 100% of patients harbor either the JAK2V617F or JAK2 exon 12 mutations. In a phase 2 study in HU-resistant or -intolerant PV patients, ruxolitinib, a potent and selective inhibitor of JAK1/JAK2, was well tolerated and achieved rapid and durable clinical responses, including phlebotomy independence, resolution of splenomegaly, and improvements in white blood cell (WBC) and platelet (PLT) counts and disease-related symptoms. Methods: RESPONSE is a randomized (1:1), open-label, global phase 3 study (NCT01243944) designed to compare the safety and efficacy of ruxolitinib with best available therapy (BAT) in adult patients with PV who are resistant to or intolerant of HU (modified European Leukemia Net criteria) and require phlebotomy because of inadequate hematocrit control. Inclusion criteria have been amended to include patients who exhibit palpable splenomegaly with an MRI-confirmed volume of ≥ 450 cm3 (ie, approximately 2.5 x median normal volume; instead of ≥ 5 cm by palpation) and PLT > 100 x109/L; the requirement for either elevated WBC (> 15 x109/L) or PLT count (> 600 x109/L) was removed. The primary efficacy endpoint is the achievement of both phlebotomy independence and a ≥ 35% reduction in spleen volume after 32 weeks of treatment. Patients will be treated for 80 weeks to assess safety and durability of response. Patients randomized to BAT may be eligible to cross over to receive ruxolitinib after week 32. Enrollment is planned for 145 investigational sites (134 currently open), with a target of 200 patients.

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