Iodixanol in Abdominal Digital Subtraction Angiography

1993 ◽  
Vol 34 (3) ◽  
pp. 242-245 ◽  
Author(s):  
K. Singh ◽  
R. Sundgren ◽  
B. Bolstad ◽  
L. Björk ◽  
M. Lie
Keyword(s):  
Adverse Events ◽  
Clinical Importance ◽  
Diagnostic Information ◽  
Phase Iii ◽  
Digital Subtraction ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Phase Iii Trial ◽  
The Mean ◽  
The Difference

The safety, tolerability and efficacy of iodixanol 270 mg I/ml were compared to those of iohexol 300 mg I/ml in a double-blind, randomized, parallel abdominal intra-arterial DSA phase III trial. Fifty-nine patients were included in the trial; 39 patients received iodixanol and 20 received iohexol. The mean volume of iodixanol administered was 235.8 ml (0.93 g I/kg b.w.) while the mean volume of iohexol was 254.7 ml (1.10 g I/kg b.w.). No differences in diagnostic information and radiographic density were apparent in spite of the difference in the concentration of iodine. No serious adverse events occurred. Four patients (10%) in the iodixanol group and 2 (10%) in the iohexol group experienced adverse events. Eight percent of the injections of iodixanol promoted discomfort, compared to 12%) of the injections of iohexol. An increase in S-urea and S-creatinine was seen with both agents the first day after injection, but appeared to be less pronounced with iodixanol than with iohexol. Other serum tests revealed no changes of clinical importance. Both iodixanol and iohexol were found to be effective, safe and well tolerated contrast media for abdominal intra-arterial DSA.

scholarly journals P131 Efficacy and safety of olokizumab in a phase III trial of patients with moderately to severely active RA inadequately controlled by methotrexate: placebo and active controlled study

Rheumatology ◽  
2021 ◽  
Vol 60 (Supplement_1) ◽  
Author(s):  
Eugen Feist ◽  
Saima Chohan ◽  
Saeed Fatenejad ◽  
Sergey Grishin ◽  
Elena Korneva ◽  
...  
Keyword(s):  
Adverse Events ◽  
Randomised Clinical Trial ◽  
Phase Iii ◽  
Controlled Study ◽  
Open Label ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Acr20 Response ◽  
Phase Iii Trial ◽  
Secondary Endpoints

Abstract Background/Aims  Olokizumab (OKZ) is a new humanised monoclonal antibody targeting IL-6 directly. Here we present the results of a global randomised clinical trial (RCT) in patients (pts) with RA. Methods  This double-blind, placebo (PBO) and active controlled, RCT in pts with moderately to severely active RA despite MTX (ClinicalTrials.gov Identifier NCT02760407, CREDO2) was carried out in 18 counties. Pts were randomized 2:2:2:1 to receive subcutaneous injections of OKZ 64 mg every 2 weeks (q2w), OKZ 64 mg once every 4 weeks (q4w), adalimumab (ADA) 40mg q2w or PBO for 24 weeks, plus MTX. After week 24, subjects either rolled over into an open-label study or entered the Safety Follow-Up Period for another 20 weeks. The primary endpoint was ACR 20% (ACR20) response rate at week 12. Secondary endpoints included: percentage of subjects with DAS28-CRP <3.2 and improvement of HAQ-DI from baseline at week 12, ACR50 and percentage of subjects with remission (CDAI) ≤2.8 at week 24. Safety outcomes, including adverse events, serious adverse events and laboratory abnormalities were assessed. Results  1,648 subjects were randomised to OKZ 64mg q2w (n = 464), OKZ 64mg q4w (n = 479), ADA 40mg (n = 462) or PBO (n = 243). Baseline characteristics were comparable across treatment arms. The vast majority of the pts completed 24 weeks treatment period 421 (90.7%) in q2w, 437 (91.2%) in q4w, 413 (89.4%) in ADA and 208 (85.6%) in PBO arms and enrolled to open-label extension study: 410 (88.4%), 422 (88.1%), 397 (85.9%) and 199 (81.9%) pts, respectively. Both regimens of OKZ were significantly better than PBO in all primary and secondary endpoints. Furthermore, non-inferiority to ADA was demonstrated for the pre-defined endpoints of ACR20 and DAS28-CRP<3.2 for both OKZ treatment groups. The efficacy outcomes were maintained throughout the 24-week period of the study. Overall incidence of treatment-emergent adverse events (TEAEs) was 70.0% in OKZ q2w arm; 70.9% in OKZ q4w arm, 65.4% in ADA arm and 63.4% in PBO, TEAEs leading to study treatment discontinuation were reported in 4.5%, 6.3%, 5.6% and 3.7% pts, respectively. The number of deaths were comparable among arms: 3 (0.6%; 2 infections, 1 cerebrovascular accident) in the OKZ q2w arm, 2 (0.4%; 1 infection, 1 myocardial ischemia) in OKZ q4w arm, 1 (0.2%; infection) in ADA arm and 1 (0.4%; sudden death) in PBO. The most common treatment-emergent serious adverse events (TESAEs) were infections. Conclusion  In this global Phase III trial, treatment with OKZ plus MTX in both regimes (OKZ 64 mg q2w and OKZ 64 mg q4w) was associated with significant improvements in the signs, symptoms and physical function of RA compared to PBO plus MTX and non-inferior to ADA plus MTX over a 24-week period. OKZ was well tolerated and no new safety signals were observed. Disclosure  E. Feist: Consultancies; R-Pharm, Abbvie, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi. Honoraria; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Member of speakers’ bureau; R-Pharm, Abbvie, AB2Bio, BMS, Celgene, Janssen, Lilly, Medac, MSD, Novartis, Pfizer, Roche/Chugai, Sanofi, Sobi, UCB. Grants/research support; Lilly, Novartis, Pfizer, Roche/Chugai. S. Chohan: None. S. Fatenejad: Consultancies; RPharm International. Shareholder/stock ownership; Pfizer. S. Grishin: Corporate appointments; Employed by R-Pharm. E. Korneva: Corporate appointments; Employed by R-Pharm. E.L. Nasonov: Honoraria; Lilly, Abbnie, Prizer, Biocad, R-Pharm. Member of speakers’ bureau; Lilly, Abbnie, Prizer, Biocad, R-Pharm. A. Rowińska-Osuch: Consultancies; R-Pharm. M. Samsonov: Corporate appointments; Employed by R-Pharm.

scholarly journals Phase III double-blind study comparing the efficacy and safety of proposed biosimilar MYL-1402O and reference bevacizumab in stage IV non-small-cell lung cancer

2021 ◽  
Vol 13 ◽  
pp. 175883592110458
Author(s):  
Mark A. Socinski ◽  
Cornelius F. Waller ◽  
Tazeen Idris ◽  
Igor Bondarenko ◽  
Alexander Luft ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Adverse Events ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Small Cell ◽  
Phase Iii ◽  
European Medicines Agency ◽  
Small Cell Lung ◽  
Serious Adverse Events ◽  
Double Blind

Purpose: This phase III study compared the efficacy and safety of proposed biosimilar MYL-1402O with reference bevacizumab (BEV), as first-line treatment for patients with stage IV non-squamous non-small-cell lung cancer. Patients and methods: Patients were randomly assigned (1:1) to receive MYL-1402O or bevacizumab with carboplatin-paclitaxel up to 18 weeks (6 cycles), followed by up to 24 weeks (8 cycles) of bevacizumab monotherapy. The primary objective was comparison of overall response rate (ORR), based on independently reviewed best tumor responses as assessed during the first 18 weeks. ORR was analyzed per US Food and Drug Administration (ratio of ORR) and European Medicines Agency (difference in ORRs) requirements for equivalence evaluation. Secondary end points included progression-free survival, disease control rate, duration of response, overall survival, safety, and immunogenicity over a period of 42 weeks, and pharmacokinetics (up to 18 weeks). Results: A total of 671 patients were included in the intent-to-treat population. The ratio of ORR was 0.96 [confidence interval (CI) 0.83, 1.12] and the difference in ORR was −1.6 (CI −9.0, 5.9) between treatment arms; CIs were within the predefined equivalence margins. Overall, the incidence of treatment-emergent adverse events and serious adverse events was comparable. Treatment-emergent anti-drug antibody (ADA) positivity was transient, with no notable differences between treatment arms (6.5% versus 4.8% ADA positivity rate in MYL-1402O versus BEV, respectively). The incidence of neutralizing antibody post-baseline was lower in the MYL-1402O arm (0.6%) compared to the bevacizumab arm (2.5%). Conclusions: MYL-1402O is therapeutically equivalent to bevacizumab, based on the ORR analyses, with comparable secondary endpoints. Trial Registry Information EU Clinical Trials Register, Registration # EudraCT no. 2015-005141-32 https://www.clinicaltrialsregister.eu/ctr-search/search?query=2015-005141-32 Plain language summary Previous studies established bioequivalence of the proposed bevacizumab biosimilar MYL-1402O to reference bevacizumab. In this randomized, double-blind, phase III trial, MYL-1402O ( n = 337) demonstrated comparable efficacy to bevacizumab ( n = 334) in treating advanced non-squamous non-small-cell lung cancer per Food and Drug Administration and European Medicines Agency requirements for equivalence; the ratio of objective response rate (ORR) was 0.96 [90% confidence interval (CI) 0.83, 1.12] and the difference in ORR (MYL-1402O:bevacizumab) was −1.6 (95% CI −9.0, 5.9). Median progression-free survival at 42 weeks was comparable: 7.6 (7.0, 9.5) with MYL-1402O versus 9.0 (7.2, 9.7) months ( p = 0.0906) with bevacizumab, by independent review. Treatment-emergent adverse events leading to death (2.4% vs 1.5%), serious adverse events (17.6% vs 16.7%), and antidrug antibodies (6.5% vs 4.8%), were comparable in the MYL-1402O vs bevacizumab arms, respectively. The incidence of neutralizing antibody post-baseline was lower with MYL-1402O (0.6%) than with bevacizumab (2.5%). These findings confirm therapeutic equivalence of MYL-1402O to bevacizumab, providing opportunities for improving access to bevacizumab.

scholarly journals 2724. Safety and Immunogenicity of a Quadrivalent Meningococcal Conjugate Vaccine (MenACYW-TT) Administered in Healthy Meningococcal Vaccine-Naïve Children (2–9 Years)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S958-S959
Author(s):  
Michael W Simon ◽  
Donald Brandon ◽  
Shane Christensen ◽  
Carmen Baccarini ◽  
Emilia Jordanov ◽  
...  
Keyword(s):  
Adverse Events ◽  
Injection Site ◽  
Conjugate Vaccine ◽  
Safety Data ◽  
Phase Iii ◽  
Meningococcal Vaccine ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Post Vaccination ◽  
Quadrivalent Meningococcal Conjugate Vaccine

Abstract Background MenACYW-TT is an investigational quadrivalent meningococcal conjugate vaccine that contains tetanus toxoid as carrier protein. The vaccine is intended for global use in individuals 6 weeks of age and older. We evaluated the safety and immunogenicity of MenACYW-TT compared with a licensed quadrivalent conjugate meningococcal vaccine (MenACWY-CRM [Menveo®]) in US children 2–9 years of age. Methods In a modified double-blind Phase III study (NCT03077438), 1000 children were randomized to receive one dose of either MenACYW-TT vaccine or MenACWY-CRM vaccine. Serum bactericidal assays with human (hSBA) and baby rabbit (rSBA) complement were used to measure antibodies against representative meningococcal serogroup strains at baseline and 30 days after vaccination. Safety data were collected up to 6 months post-vaccination. Results Non-inferiority of immune responses for all four serogroups, based on percentages of participants achieving hSBA vaccine seroresponse, was demonstrated for MenACYW-TT compared with MenACWY-CRM at Day 30 compared with baseline. The proportions of individuals with hSBA titers ≥ 1:8 following MenACYW-TT administration were higher than those after MenACWY-CRM administration for all four serogroups (A: 86.4% vs 79.3%; C: 97.8% vs 67.1%; W: 94.8% vs 86.3%; Y: 98.5% vs 90.8%). Similar results were observed in two age substrata (2 to 5 years and 6 to 9 years). Percentages of participants with post-vaccination rSBA titers ≥ 1:128 were comparable between both groups. The safety profiles of MenACYW-TT and MenACWY-CRM were comparable. Reactogenicity at the MenACYW-TT injection site was lower than at the MenACWY-CRM injection site. There were no immediate adverse events (AEs), no AEs leading to study discontinuation, and no vaccine-related serious adverse events reported in the study. Conclusion MenACYW-TT vaccine was well tolerated and demonstrated a non-inferior immune response compared with that for the licensed MenACWY-CRM vaccine when administered as a single dose to meningococcal vaccine-naïve children. Disclosures All authors: No reported disclosures.

A Comparison of Proposed Biosimilar and Originator Filgrastim for the Prevention of Neutropenia in Patients with Breast Cancer Receiving Myelosuppressive Adjuvant or Neoadjuvant Chemotherapy: Phase III, Randomized, Double-Blind Trial (The PIONEER study)

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5133-5133 ◽  
Author(s):  
Kimberly Blackwell ◽  
Vladimir Semiglazov ◽  
Pedro Gascon ◽  
Roumen Nakov ◽  
Stefan Kramer ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Treatment Group ◽  
Adverse Events ◽  
Lower Limit ◽  
Study Drug ◽  
Phase Iii ◽  
Efficacy And Safety ◽  
Double Blind ◽  
Pioneer Study ◽  
The Mean

Abstract Introduction: Biosimilars are biologics which have demonstrated highly similar safety, potency and purity to an originator product. Several biosimilars of recombinant human filgrastim, based on the originator Neupogen®, have become available in Europe since 2008 and are now in clinical use for the prevention of chemotherapy-induced neutropenia and hematopoietic stem cell mobilization. Filgrastim biosimilars are presently being developed for the U.S. market. Study design: A randomized, double-blind, four-group, multi-center phase III non-inferiority trial was performed with breast cancer patients treated with myleosuppressive chemotherapy. The two filgrastim products – proposed biosimilar, EP2006 (“biosimilar”) vs. originator (U.S.-licensed Neupogen®) - were compared regarding efficacy and safety. Patients included: women ≥18 years with histologically-proven breast cancer eligible for neoadjuvant or adjuvant treatment with docetaxel 75 mg/m2, doxorubicin 50 mg/m2 and cyclophosphamide 500 mg/m2 (TAC regimen) given for 6 cycles. Other key inclusion criteria included: Eastern Cooperative Oncology Group performance status ≤2 and adequate bone marrow function. Eligible patients were randomized to 4 groups with 2 of these groups alternating between the biosimilar and the originator filgrastim at the end of each cycle: 1) EP: treatment with EP2006 in all cycles; 2) EPNEU: EP2006 in Cycle 1, alternating between Neupogen and EP2006 in the following cycles; 3) NEUEP: Neupogen in Cycle 1, alternating between EP2006 and Neupogen in the following cycles; 4) NEU: treatment with Neupogen in all cycles. Patients received either biosimilar or originator filgrastim subcutaneously (daily dose of 5 µg/kg body weight) starting on Day 2 of each chemotherapy cycle until the absolute neutrophil count (ANC) recovered to 10×109/L after nadir or up to 14 days. Total duration of the study was 25 weeks: 3 weeks screening, 18 weeks treatment (total 6 cycles, 3 weeks each) and a follow-up visit 4 weeks after the last study drug administration. Primary objective was to assess the efficacy of the biosimilar compared to the originator with respect to mean duration of severe neutropenia (DSN) following Cycle 1 chemotherapy. A one-sided 97.5% confidence interval (CI) for the difference in the mean DSN calculated using ANCOVA model with factors “treatment” and “kind of therapy” and covariates “baseline ANC” was to be considered non-inferior if lower limit of this CI lies entirely above non-inferiority margin of -1 day. All secondary efficacy endpoints and safety endpoints were analyzed descriptively by treatment group. The study was conducted between December 2011 and June 2013. Results: Enrolled were 258 patients in 27 centers, of which 218 patients were randomized to treatment. The baseline characteristics were balanced between different groups. The per-protocol set included 204 patients out of 218 randomized patients. The safety set included 214 patients who received at least one dose of study drug. On average each patient received treatment for 8-9 days per cycle. The mean DSN in Cycle 1 was 1.17±1.11 days (biosimilar) and 1.20±1.02 days (originator); the mean difference in DSN was 0.04 days (97.5% CI, lower limit -0.26 days). The pre-defined non-inferiority criteria were met and the biosimilar was considered non-inferior to the originator filgrastim. The incidence of febrile neutropenia over all 6 cycles chemotherapy was comparably low in all treatment groups (EP: 2/40, 5.0%, EPNEU: 5/45, 11.1%, NEUEP: 1/44, 2.3%, NEU: 0/46, 0.0%). There was no obvious difference in incidences of treatment emergent adverse events between the treatment arms. Twelve patients experienced serious adverse events (EP: 5/53, 9.4% patients; EPNEU: 4/54, 7.4%; NEUEP: 1/55, 1.8%; NEU: 2/52, 3.8%). None of them were study drug related, including one death (in the EP treatment group due to pulmonary embolism). No subjects developed anti-drug antibodies. Conclusion: This large clinical study showed that efficacy and safety of the biosimilar was comparable to the originator filgrastim in prevention of neutropenia in patients with breast cancer. Repeated switching between the biosimilar and the originator filgrastim did not impact efficacy, safety or immunogenicity. Acknowledgment: The authors acknowledge the other investigators of the PIONEER study and acknowledge Gabor Stiegler, Sandoz Biopharmaceuticals for the medical writing. Disclosures Blackwell: Sandoz Biopharmaceuticals: Consultancy. Semiglazov:Sandoz Biopharmaceuticals: Consultancy. Gascon:Sandoz Biopharmaceuticals: Consultancy. Nakov:Sandoz Biopharmaceuticals: Employment. Kramer:Sandoz Biopharmaceuticals: Employment. Schwebig:Sandoz Biopharmaceuticals: Employment. Harbeck:Sandoz Biopharmaceuticals: Consultancy.

scholarly journals Safety and immunogenicity of a seasonal trivalent inactivated split influenza vaccine: a double blind, phase III randomized clinical trial in healthy Serbian adults

2020 ◽  
Vol 8 ◽  
pp. 251513552092533
Author(s):  
Goran Stevanovic ◽  
Aleksandar Obradovic ◽  
Snezana Ristic ◽  
Dragan Petrovic ◽  
Branislava Milenkovic ◽  
...  
Keyword(s):  
Adverse Events ◽  
Influenza Vaccine ◽  
Injection Site ◽  
Controlled Trial ◽  
Geometric Mean ◽  
Phase Iii ◽  
Serious Adverse Events ◽  
Double Blind ◽  
Post Vaccination ◽  
Robust Immune Response

This study was a phase III, multicenter, double-blind, randomized, placebo-controlled trial to evaluate the safety and immunogenicity of a seasonal trivalent split, inactivated influenza vaccine (TIV) in healthy Serbian adults between the ages of 18 and 65 years. This egg-based vaccine was manufactured by the Institute of Virology, Vaccines and Sera, Torlak, Belgrade, Serbia. A total of 480 participants were assigned randomly in a ratio of 2:1 to receive a single intramuscular dose (0.5 ml) of the vaccine (15 µg of hemagglutinin per strain) or placebo (phosphate-buffered saline). Participants were monitored for safety, including solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). No SAEs related to vaccination were reported. Injection site pain (51.3%), injection site tenderness (40.4%), tiredness (17.0%), and headache (15.1%) were the most commonly reported solicited events in the vaccine group. Incidence of related unsolicited AEs was low (1.3%) among vaccinees. Hemagglutinin inhibition (HAI) titers were measured before and 21 days after vaccination in 151 participants. Overall, HAI seroconversion rates to H1 and H3 were observed in 90.1% and 76.2% of vaccinees, respectively. For B antigen, it was 51.5%, likely due to high pre-vaccination titers. Post-vaccination seroprotection rates were in the range of 78.2–95.0% for the three antigens. Post-vaccination geometric mean titers (GMT) were at least 3.8 times higher than baseline levels for all the three strains among vaccinees. Overall, the study showed that the vaccine was safe and well tolerated, and induced a robust immune response against all three vaccine strains. ClinicalTrials.gov identifier: NCT02935192, October 17, 2016

scholarly journals Analisi di costo di pemetrexed vs docetaxel nel trattamento di seconda linea del carcinoma polmonare non a piccole cellule

2005 ◽  
Vol 6 (2) ◽  
pp. 119-126
Author(s):  
Roberto Ravasio
Keyword(s):  
Adverse Events ◽  
Cost Analysis ◽  
Cost Utility ◽  
Phase Iii ◽  
Chemotherapy Drugs ◽  
Study Results ◽  
Previously Treated ◽  
The Mean ◽  
The Difference ◽  
Mean Cost

OBJECTIVES: to compare costs of pemetrexed versus docetaxel in patients with non-small cell lung cancer previously treated with chemotherapy paying special attention to the adverse events. MATERIALS AND METHODS: a cost analysis was carried out performing comparison between pemetrexed and docetaxel. Clinical data (overall survival) and resource consumption (chemotherapy drugs, G-CSF, and hospitalizations due to adverse events) were obtained from a randomized phase III trial. The economic evaluation was based on direct costs using local Italian unit costs (euro 2005). The perspective was the National Health Service’s. RESULTS: the study results showed that mean survival of pemetrexed (8,3 months; 0,69 years) was higher than mean survival of docetaxel (7,9 months; 0,66 years). The mean cost of treatment with pemetrexed was 8.684,26 euros and with docetaxel was 6.182,87 euros. This difference was nearly offset by the difference in the costs of adverse events: the mean cost of adverse events due to chemotherapy treatment with pemetrexed (493,93 euros) turned out to be lower than with docetaxel (2.394,34 euros). CONCLUSION: the present cost-analysis could be a stable ground for a further cost-utility analysis, aimed at reaching a more cost-effectiveness management of the chemotherapy-related adverse effects in patients with NSCLC.

scholarly journals Commentary on Article: Efficacy of a Tetravalent Dengue Vaccine in Healthy Children and Adolescents (NEJM, Nov 21 2019)

2020 ◽  
pp. 21-28
Author(s):  
A. M. Meer Ahmad
Keyword(s):  
Adverse Events ◽  
Children And Adolescents ◽  
Phase Iii ◽  
Severe Dengue ◽  
Healthy Children ◽  
Additional Observation ◽  
Dengue Vaccine ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Chimeric Vaccine

In this Letter to the Editor, this author comments on the article in the NEJM (Nov 21 2019) in the above title on the TAK-003 Dengue vaccine Phase III trial from a point of comparing with the predecessor, the CYD-TDV, beside comparing the TAK-003 and Severe dengue, and the TAK-003 and hospitalizations. The author also queries why the vaccine must be a chimeric-vaccine, questions the sample-size in the Phase III trial and questions the Serious Adverse Events reported observed in the trial. He write on Antibody Directed Enhancement in a relation to the TAK-003. The author make Additional Observation and seek certain Explanation.

A randomized, double-blind, phase III study comparing SB3 (trastuzumab biosimilar) with originator trastuzumab in patients treated by neoadjuvant therapy for HER2-positive early breast cancer.

2017 ◽  
Vol 35 (15_suppl) ◽  
pp. 509-509 ◽  
Author(s):  
Xavier B. Pivot ◽  
Igor Bondarenko ◽  
Mikhail Dvorkin ◽  
Ekaterina Trishkina ◽  
Jin-Hee Ahn ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Adverse Events ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Phase Iii ◽  
Her2 Positive ◽  
Double Blind ◽  
Secondary Endpoints ◽  
The Difference ◽  
Equivalence Margin

509 Background: SB3, a proposed biosimilar to the originator trastuzumab (TRZ), demonstrated similarity to its originator in terms of biological activities and pharmacokinetic (PK) equivalence. This study compared SB3 to TRZ in terms of efficacy, safety, PK, and immunogenicity in patients treated by neoadjuvant therapy for HER2 positive early breast cancer (NCT02149524). Methods: Phase III, randomized, double blind, multicenter study compared neoadjuvant SB3 or TRZ for 8 cycles concurrently given with chemotherapy (docetaxel followed by 5-fluorouracil/epirubicin/cyclophosphamide). Then patients underwent surgery followed by 10 cycles of SB3 or TRZ. The primary endpoint was breast pathologic complete response (bpCR) rate. Equivalence was declared if the 90% confidence interval (CI) of the ratio or the 95% CI of the difference of the bpCR rates in the per-protocol set (PPS) were contained within the pre-defined equivalence margins (0.785, 1.546) and (-13%, 13%), respectively. Secondary endpoints were total pathologic complete response (tpCR), overall response rate (ORR), event-free survival, PK, immunogenicity, and safety. Results: 800 patients were included in PPS. The bpCR rates were 51.7% for SB3 and 42.0% for TRZ. The ratio of bpCR rate was 1.259 and its 90% CI was 1.112-1.426, within the pre-defined equivalence margin. The difference of bpCR rate was 10.70% and its 95% CI was 4.13-17.26; the lower margin was contained within, the upper margin was outside the pre-defined equivalence margin. Secondary endpoints were comparable between SB3 vs TRZ: tpCR rate (45.8% vs 35.8%); ORR (96.3% vs 91.2%). Safety was comparable between SB3 vs TRZ during neoadjuvant period: incidence of treatment-emergent adverse events (96.6% vs 95.2%), most commonly neutropenia, alopecia, and nausea; incidence of serious adverse events (10.5% vs 10.7%). PK equivalence was demonstrated and immunogenicity between SB3 vs TRZ was comparable (0.7% vs 0.0%). Conclusions: Equivalence was demonstrated between SB3 and TRZ based on the ratio of bpCR rates. Safety, PK, and immunogenicity were similar. Complete safety and survival data will follow. Clinical trial information: NCT02149524.

Randomized, Open-Label Phase III Trial of Docetaxel Plus High-Dose Calcitriol Versus Docetaxel Plus Prednisone for Patients With Castration-Resistant Prostate Cancer

2011 ◽  
Vol 29 (16) ◽  
pp. 2191-2198 ◽  
Author(s):  
Howard I. Scher ◽  
Xiaoyu Jia ◽  
Kim Chi ◽  
Ronald de Wit ◽  
William R. Berry ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Adverse Events ◽  
Phase Iii ◽  
High Dose ◽  
Castration Resistant Prostate Cancer ◽  
Open Label ◽  
Serious Adverse Events ◽  
Phase Iii Trial ◽  
Castration Resistant ◽  
Open Label Phase

Purpose To compare the efficacy and safety of docetaxel plus high-dose calcitriol (DN-101) to docetaxel plus prednisone in an open-label phase III trial. Patients and Methods Nine hundred fifty-three men with metastatic castration-resistant prostate cancer (CRPC) were randomly assigned to Androgen-Independent Prostate Cancer Study of Calcitriol Enhancing Taxotere (ASCENT; 45 μg DN-101, 36 mg/m2 docetaxel, and 24 mg dexamethasone weekly for 3 of every 4 weeks) or control (5 mg prednisone twice daily with 75 mg/m2 docetaxel and 24 mg dexamethasone every 3 weeks) arms. The primary end point was overall survival (OS), assessed by the Kaplan-Meier method. Results At an interim analysis, more deaths were noted in the ASCENT arm, and the trial was halted. The median-follow-up for patients alive at last assessment was 11.7 months. Median OS was 17.8 months (95% CI, 16.0 to 19.5) in the ASCENT arm and 20.2 months (95% CI, 18.8 to 23.0) in the control arm (log-rank P = .002). Survival remained inferior after adjusting for baseline variables (hazard ratio, 1.33; P = .019). The two arms were similar in rates of total and serious adverse events. The most frequent adverse events were GI (reported in 75% of patients), and blood and lymphatic disorders (48%). Docetaxel toxicity leading to dose modification was more frequent in the ASCENT (31%) than in the control arm (15%). Conclusion ASCENT treatment was associated with shorter survival than the control. This difference might be due to either weekly docetaxel dosing, which, in a prior study, showed a trend toward inferior survival compared with an every-3-weeks regimen, or DN-101 therapy.

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