scholarly journals Phase III anti-HIV microbicide trial in Africa and India stopped as preliminary results show gel may increase risk of infection

2007 ◽  
Vol 12 (6) ◽  
Author(s):  
Collective Editorial team
Keyword(s):  
Placebo Group ◽  
Hiv Infection ◽  
Phase Iii ◽  
Risk Of Infection ◽  
Phase Iii Trial ◽  
Microbicide Trial ◽  
Increase Risk ◽  
Group A ◽  
Hiv Microbicide ◽  
Anti Hiv

A Phase III trial of a candidate microbicide gel to prevent HIV infection in women has been halted because more participants using the gel were becoming infected than those in the placebo group. A trial of the same gel in Nigeria has also been stopped as a precaution.

scholarly journals Effectiveness of Cellulose Sulfate Vaginal Gel for the Prevention of HIV Infection: Results of a Phase III Trial in Nigeria

PLoS ONE ◽  
2008 ◽  
Vol 3 (11) ◽  
pp. e3784 ◽  
Author(s):  
Vera Halpern ◽  
Folasade Ogunsola ◽  
Orikomaba Obunge ◽  
Chin-Hua Wang ◽  
Nneka Onyejepu ◽  
...  
Keyword(s):  
Hiv Infection ◽  
Phase Iii ◽  
Cellulose Sulfate ◽  
Phase Iii Trial ◽  
Vaginal Gel ◽  
Prevention Of Hiv

Survival and safety of monosialotetrahexosylganglioside in GI cancer patients with oxaliplatin-induced peripheral neurotoxicity-result from TJMUCH-GI-001 trial.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 11596-11596
Author(s):  
Zhou Likun ◽  
Dingzhi Huang ◽  
Rui Liu ◽  
Hongli Li ◽  
Tao Ning ◽  
...  
Keyword(s):  
Placebo Group ◽  
Adverse Events ◽  
Cancer Patients ◽  
Survival Data ◽  
Phase Iii ◽  
Rank Test ◽  
Peripheral Neurotoxicity ◽  
Phase Iii Trial ◽  
Gi Cancer

11596 Background: TJMUCH-GI-001 Trial was a randomized, double-blind, placebo-controlled phase III trial to study the efficacy of Monosialotetrahexosylganglioside (GM1) for oxaliplatin-induced peripheral neurotoxicity (OIPN) in GI cancer patients. Majority patients (> 80%) in both arms continued receiving oxaliplatin on the trial. The results showed GM1 effectively reduced OIPN in GI cancer patients. Here we report the survival and safety results of this trial. Methods: Patients were randomized in a 1:1 ratio to receive GM1 or placebo. Patients with OIPN > = G2 by CTCAE 4.03 persisting during or after oxaliplatin-based chemotherapy were eligible. The patients who remained on oxaliplatin after enrollment, received concurrent placebo or GM1 x 7 days with each chemotherapy cycle. The patients who stopped taking oxaliplatin, were treated with placebo or GM1 x 14 days every 3 weeks. GM1 was dosed at 60mg daily for every 3-week or 40mg daily for every 2-week schedule. Trial was continued until modified EORTC QLQ-CIPN20 ( MCIPN) increased by 30% or stayed unchanged after two more treatments beyond completion of oxaliplatin. Survival data for the treatment arms were compared using a log-rank test and Chi-square tests were used for safety analysis. Results: From May 2015 to Dec 2017, 73 patients were enrolled in GM1 and 72 in placebo arm. The median follow-up was 16.6 months (0.8-43.1 months) as of Dec.2018. Four patients lost to follow up. There was no deleterious impact of GM1 on survival. As a matter of fact, receiving GM1 was associated with a trend toward improved PFS and OS (HR=0.74,95%CI, 0.469 - 1.156 for PFS and HR=0.76, 95%CI0.469 - 1.156 for OS). The most frequent Grade 3 or 4 adverse events included neutropenia (8 patients in GM1 group VS. 4 in placebo group) and hypoleukemia (4 patients in GM1 group VS. 1 in placebo group). Other 3 or 4 adverse events (all less than 3 patients) included anorexia, hypercalcemia, nausea, vomiting, proteinuria, hyperbilirubinemia, hypokalemia, hypertension and appendicitis. All the 3 or 4 adverse events were related to chemotherapy, not to GM1. Conclusion: In this placebo-controlled phase III trial, GM1 showed acceptable toxicity with trends favorable PFS and OS in GI cancer patients. Clinical trial information: NCT02486198.

EXPERT study: Randomized phase III trial of radical surgery and postoperative mFOLFOX6 versus perioperative mFOLFOX6 plus cetuximab in patients with KRAS wild-type resectable colorectal liver metastases (CLMs).

2019 ◽  
Vol 37 (4_suppl) ◽  
pp. 652-652 ◽  
Author(s):  
Yoshihiro Mise ◽  
Kiyoshi Hasegawa ◽  
Masaru Oba ◽  
Kensei Yamaguchi ◽  
Hiroyuki Uetake ◽  
...  
Keyword(s):  
Liver Metastases ◽  
Medical Information ◽  
Radical Surgery ◽  
University Hospital ◽  
Phase Iii ◽  
Wild Type ◽  
Phase Iii Trial ◽  
Significant Difference ◽  
Group A ◽  
Group B

652 Background: Up-front radical surgery and adjuvant chemotherapy were regarded as one of the standard-of-care (SOC) in patients with resectablecolorectal liver metastases (CLMs), while perioperative chemotherapy plus surgery is also accepted. We conducted a multicenter randomized phase III trial to compare radical surgery and post-operative mFOLFOX6 with peri-operative mFOLFOX6 plus cetuximab in patients with KRAS wild-type resectable CLMs. Methods: Patients who had KRAS wild-type resectable CLMs having one to eight liver nodules without extrahepatic disease, were randomly assigned to groups: Group A (reference), hepatectomy and 12 cycles of post-operative mFOLFOX6: Group B (experimental), six cycles of preoperative mFOLFOX6 plus cetuximab (loading dose with 400mg/m2and thereafter 250mg/m2weekly), hepatectomy and six cycles of postoperative mFOLFOX6 plus cetuximab. Primary endpoint was progression-free survival (PFS). We hypothesized that 3-year PFS in Group B would be 25% with the hazard ratio (HR) being 0.75. Considering 3 year follow-up period with 5% of two-sided alpha error and 80% of power, target number were set as 500 (250 each). Study was registered in the University Hospital Medical Information Network (UMIN000007787). Results: This study was initiated since June 2012. However, the enrollment was terminated according to the recommendation from the monitoring committee on 2015 due to a slow accrual. A total of 77 patients (Group A 37 vs. Group B 40) were analyzed. Baseline characteristics were well-balanced between groups. Median numbers of liver mets were two each, ranging from one to eight. The HRs for PFS and overall survival (OS) showed no significant difference (PFS, HR = 1.18 [0.69-2.01], p = 0.54: OS, HR = 1.03 [0.46 – 2.29], p = 0.95). There were 3-year PFS of 35% in Group A vs. 30% in Group B, and 3-year OS: 86% vs. 74%, respectively. Conclusions: No additional survival benefits adding on peri-operative cetuximab were indicated, of which findings is consistent with the previous clinical studies, although there were small number of enrolled patients. Clinical trial information: UMIN000007787.

A randomized phase II multi-institutional trial of anlotinib plus docetaxel versus docetaxel in EGFR-wild-type non-small cell lung cancer (NSCLC) patients after progression on first-line platinum-base chemotherapy: ALTER-L018.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e21703-e21703
Author(s):  
Lin Wu ◽  
Zhijun Wu ◽  
Zemin Xiao ◽  
Jie Weng ◽  
Zhongsha Ma ◽  
...  
Keyword(s):  
Advanced Nsclc ◽  
Phase Iii ◽  
Wild Type ◽  
First Line ◽  
End Points ◽  
Phase Iii Trial ◽  
Platinum Based Chemotherapy ◽  
Group A ◽  
Group B ◽  
Nsclc Patients

e21703 Background: Anlotinib is an oral VEGFR, FGFR, PDGFR and c-Kit tyrosine kinase inhibitor, which can prolong both PFS and OS of refractory advanced NSCLC patients in phase III trial: ALTER0303. The combination of docetaxel and ramucirumab/nintedanib had been demonstrated activity in the second line therapy setting for NSCLC. We performed ALTER-L018 to assessed the safety and efficacy of anlotinib with docetaxel in EGFR-wild type refractory advanced NSCLC (NCT03624309). Methods: Patients (pts) with EGFR-wild type refractory advanced NSCLC, who failed to first-line platinum-based chemotherapy, were randomized to group A(anlotinib: 12mg QD from day 1 to 14 of a 21-day cycle +docetaxel: 75mg/m2 Q3W) and group B(docetaxel: 75mg/m2 Q3W). The primary end points is PFS, and secondary end points include OS, ORR, DCR and safety. Results: Between January and December 2019, 36 pts were enrolled at 10 institutions in Hunan China, with 31(15 in group A, 16 in group B) of these individuals being evaluable for treatment efficacy and safety. Pt characteristics(group A/ group B): median age: 55(39-70)/57(44-67); male: 73%/81%; non-squamous NSCLC: 86%/75%. Median PFS were 5.3 months (95%CI:2.76-7.85) in group A and 2.3 months (95%CI, 1.14-3.46) in group B (HR 0.42; 95% CI:0.16-1.13; p = 0.047); In group A and B, ORR and DCR were 26.67% versus 0%(p = 0.043), 60.00% versus 31.25%(p = 0.16), respectively. Among 31 pts, 89% of treatment-related AEs (TRAEs) were grade 1 or 2, and the most common TRAEs in group A were hand-foot syndrome, pruritus and insomnia of 13%(2/15) each; in group B were alopecia, constipation and anemia of 12%(1/16) each. Toxicities≥grade 3(TRAEs) included: neutropenia, leukopenia, diarrhea and hrombocytopenia, 6.6%(1/15) each in group A. There was 1 grade 5 AE in group A. Conclusions: This combination of anlotinib and docetaxel with significant difference PFS prolonging and manageable safety profile, is a viable option in relapsed NSCLC, should be considered following progression on platinum-based chemotherapy. It will be further explored in a randomized phase III trial. Clinical trial information: NCT03624309.

Prognostic role of MRP1 in localized high-risk soft tissue sarcoma (STS): Translational research associated to randomized phase III trial (ISG-STS 1001).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 11543-11543
Author(s):  
Javier Martin Broto ◽  
David Silva Moura ◽  
Rafael Ramos ◽  
Luca Braglia ◽  
Paola Collini ◽  
...  
Keyword(s):  
High Risk ◽  
Prognostic Value ◽  
Disease Free Survival ◽  
Phase Iii ◽  
High Dose ◽  
Prognostic Role ◽  
Phase Iii Trial ◽  
Group A ◽  
Group B ◽  
Worse Prognosis

11543 Background: The ceiling-drug effect seen for most active drugs in STS could be related, partially, to multidrug resistance mechanisms (MDRM). We previously reported the independent prognostic role for RFS and OS of MRP1 in high-risk localized STS of limbs and trunk-wall treated with epirubicin and ifosfamide (Mol Cancer Ther.2014 13(1):249-59). A translational study was carried out within the randomized phase III trial of epirubicin plus ifosfamide vs histotype-tailored neoadjuvant chemotherapy (NCT01710176), to investigate MRP1 prognostic value using the trial population as validation set. Methods: Patients enrolled in the trial were invited to participate, through the informed consent, to this analysis. IHC used QCRL-1 (Santa Cruz biotechnology) MRP1 monoclonal antibody. TMAs were built on the highest-grade area of each tumor, being the procedure blinded for clinical data. MRP1 expression was grouped as low (≤ 25% positive cells) vs high ( > 25% positive cells) expression. For data analysis, patients were grouped as A) epirubicin plus ifosfamide control arm and B) histotype-tailored experimental arm. Drugs used in group B were: gemcitabine-docetaxel (UPS), gemcitabine-DTIC (LMS), trabectedin (High-grade (HG) myxoid LPS), ifosfamide-etoposide (MPNST) and high-dose ifosfamide (SS). Prognostic value of MRP1’s extension was analyzed using Cox’s proportional hazard regression. A p-value < 0.05 was considered statistically significant. Results: 175 patients were analyzed (median age 49; males 61%) with median follow-up of 4.66 y. Group A (n = 88) included HG-myxoid LPS (27%), SS (25%), UPS (24%), LMS (12%) MPNST (10%) and others (2%); group B (n = 87) included UPS (38%), SS (24%), HG-myxoid LPS (20%), LMS (10%) and MPNST (8%). MRP1 high extension was distributed as follows: 48% (A) and 57% (B). High MRP-1 expression showed significantly worse prognosis for disease-free survival (DFS) (HR 2.71 (1.31-5.62) p = 0.007) and a trend towards worse OS (HR = 2.75 (0.97-7.81) p = 0.058) in group A. No correlation was seen between MRP-1 expression and DFS (p = 0.384) or OS (p = 0.665), in group B. Conclusions: MRP1 overexpression was related to significant worse prognosis in 2 prospective randomized series of high-risk, localized, STS treated with neoadjuvant epirubicin and ifosfamide. These agents are both substrate of MRP1; this could add rationale for a possible predictive role, as MDRM, for the two most active drugs in STS. A trial combining epirubicin, ifosfamide and MRP1 inhibitor is currently under design.

scholarly journals IMMU-03. MULTICENTER RANDOMIZED PLACEBO CONTROLLED PHASE III TRIAL OF AN AUTOLOGOUS FORMALINFIXED TUMOR VACCINE (CELLM-001) FOR NEWLY DIAGNOSED GLIOBLASTOMAS

2021 ◽  
Vol 3 (Supplement_4) ◽  
pp. iv5-iv5
Author(s):  
Yoshihiro Muragaki ◽  
Eiichi Ishikawa ◽  
Masayuki Nitta ◽  
Manabu Tamura ◽  
Tadao Ohno ◽  
...  
Keyword(s):  
Placebo Group ◽  
Tumor Vaccine ◽  
Group Versus ◽  
Good Prognosis ◽  
Phase Iii ◽  
Recent Trial ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Primary Glioblastoma ◽  
Multiple Tumor

Abstract INTRODUCTION The development of novel treatments for glioblastoma is desired and immunotherapy is theoretically expected for highly invasive glioblastoma. An autologous formalin-fixed vaccine (AFTV) derived from resected tumor tissue is stable, contains multiple tumor peptides, and could induce specific immunity. We have conducted three clinical trials in patients with glioblastoma, and the most recent trial was a double-blind, multicenter, phase IIb trial with 63 case enrollments. Although this Phase IIb study revealed no vaccine effects in the whole cohort (mOS: 25.6 months of AFTV group, 31.5 months of the placebo group), the 3-year PFS for patients with total tumor removal was 81% in the AFTV group versus 46% in the placebo group (P=0.067). AFTV vaccine (Cellm-001) may have an effect on certain patient subgroups, and a Phase III study has started in November 2021 (jRCT2031200153). Based on Phase IIb, the enrolled patients were those who could be completely resected on MRI. Cellm-001 administration to a patient in the placebo group at recurrence (crossover) was prohibited. In addition, photodynamic therapy (PDT) was added as a stratification factor because our retrospective study showed a good prognosis of 19 patients who underwent both PDT and AFTV (mOS 47.7 months). PATIENTS AND METHODS Trial design: double-blind (1: 1), phase III multicenter, registration 4 years, observation 2 years. ESTIMATED ENROLLMENT: 112 patients with primary glioblastoma (18-75 years old) whose contrast-enhanced lesion could be completely removed on the image and who received standard local radiotherapy and temozolomide chemotherapy. STRATIFICATION FACTORS: presence or absence of PDT, age, KPS. ADMINISTRATION METHOD: Intradermal administration 3 times before radiochemotherapy and 6 times in parallel with maintenance chemotherapy after completion. PRIMARY ENDPOINT: OS, secondary endpoints: PFS and adverse events. https://jrct.niph.go.jp/en-latest-detail/jRCT2031200153. CONCLUSION An investigator-initiated phase III trial will investigate the efficacy and safety of unique AFTV immunotherapy.

scholarly journals Tocilizumab in patients with adult-onset still’s disease refractory to glucocorticoid treatment: a randomised, double-blind, placebo-controlled phase III trial

2018 ◽  
Vol 77 (12) ◽  
pp. 1720-1729 ◽  
Author(s):  
Yuko Kaneko ◽  
Hideto Kameda ◽  
Kei Ikeda ◽  
Tomonoti Ishii ◽  
Kosaku Murakami ◽  
...  
Keyword(s):  
Placebo Group ◽  
Phase Iii ◽  
Adult Onset Still’S Disease ◽  
Adult Onset ◽  
Still’S Disease ◽  
Double Blind ◽  
Phase Iii Trial ◽  
Systemic Feature ◽  
Still's Disease ◽  
Adult Onset Still's Disease

ObjectiveTo evaluate the efficacy and safety of tocilizumab, an interleukin-6 receptor antibody, in patients with adult-onset Still’s disease.MethodsIn this double-blind, randomised, placebo-controlled phase III trial, 27 patients with adult-onset Still’s disease refractory to glucocorticoids were randomised to tocilizumab at a dose of 8 mg/kg or placebo given intravenously every 2 weeks during the 12-week, double-blind phase. Patients received open-label tocilizumab for 40 weeks subsequently. The primary outcome was American College of Rheumatology (ACR) 50 response at week 4. The secondary outcomes included ACR 20/50/70, systemic feature score, glucocorticoid dose and adverse events at each point.ResultsIn the full analysis set, ACR50 response at week 4 was achieved in 61.5% (95% CI 31.6 to 86.1) in the tocilizumab group and 30.8% (95% CI 9.1 to 61.4) in the placebo group (p=0.24). The least squares means for change in systemic feature score at week 12 were –4.1 in the tocilizumab group and –2.3 in the placebo group (p=0.003). The dose of glucocorticoids at week 12 decreased by 46.2% in the tocilizumab group and 21.0% in the placebo group (p=0.017). At week 52, the rates of ACR20, ACR50 and ACR70 were 84.6%, 84.6% and 61.5%, respectively, in both groups. Serious adverse events in all participants who received one dose of tocilizumab were infections, aseptic necrosis in the hips, exacerbation of adult-onset Still’s disease, drug eruption and anaphylactic shock.ConclusionThe study suggests that tocilizumab is effective in adult-onset Still’s disease, although the primary endpoint was not met and solid conclusion was not drawn.

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