scholarly journals Bicalutamide (‘Casodex’) 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme

2005 ◽  
Vol 8 (2) ◽  
pp. 194-200 ◽  
Author(s):  
M Wirth ◽  
◽  
C Tyrrell ◽  
K Delaere ◽  
M Sánchez-Chapado ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Standard Care ◽  
Phase Iii ◽  
Double Blind ◽  
Early Prostate Cancer ◽  
Phase Iii Study

Phase III study of androgen deprivation therapy (ADT) with enzalutamide (ENZA) or placebo (PBO) in metastatic hormone-sensitive prostate cancer (mHSPC): The ARCHES trial.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 687-687 ◽  
Author(s):  
Andrew J. Armstrong ◽  
Russell Zelig Szmulewitz ◽  
Daniel Peter Petrylak ◽  
Arnauld Villers ◽  
Arun Azad ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
High Volume ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
Secondary Endpoints ◽  
Phase Iii Study ◽  
Grade 3

687 Background: ENZA, a potent androgen receptor inhibitor, has demonstrated benefit in men with metastatic and nonmetastatic castration-resistant prostate cancer (CRPC). Efficacy of ENZA with ADT in men with mHSPC is unknown. Methods: ARCHES is a multinational, double-blind, phase 3 study (NCT02677896). Patients (pts) with mHSPC were randomized 1:1 to ENZA (160 mg/day) + ADT or PBO + ADT, stratified by disease volume (CHAARTED criteria) and prior docetaxel therapy. Primary endpoint was radiographic progression-free survival (rPFS) assessed centrally or death within 24 weeks of treatment discontinuation. Secondary endpoints included time to prostate-specific antigen (PSA) progression, PSA and radiographic responses and overall survival (OS). Treatment continued until disease progression or unacceptable toxicity. Results: 1150 men were randomized to ENZA (n=574) or PBO (n=576); baseline characteristics were balanced between groups. Overall, 67% had distant metastasis at initial diagnosis; 63% had high volume disease, 18% had prior docetaxel. Median follow-up was 14.4 mo. ENZA + ADT significantly improved rPFS (Table); similar significant improvements in rPFS were reported in prespecified subgroups of disease volume, pattern of spread, region and prior docetaxel (HRs 0.24–0.53). Secondary endpoints improved with ENZA + ADT (Table); OS data are immature. Grade 3–4 adverse events (AEs) were reported in 23.6% of ENZA pts vs 24.7% of PBO pts with no unexpected AEs. Conclusions: ENZA + ADT significantly improved rPFS and other efficacy endpoints vs PBO + ADT in men with mHSPC, with a preliminary safety analysis that appears consistent with the safety profile of ENZA in previous CRPC clinical trials. Acknowledgements: Medical writing and editing assistance was provided by Stephanie Rippon, MBio, and Lauren Smith from Complete HealthVizion, funded by the study sponsors. This study was funded by Astellas Pharma Inc. and Medivation LLC, a Pfizer Company, the co-developers of enzalutamide. Clinical trial information: NCT02677896. [Table: see text]

scholarly journals Randomized, Double-Blind, Placebo-Controlled Phase III Study of Tasquinimod in Men With Metastatic Castration-Resistant Prostate Cancer

2016 ◽  
Vol 34 (22) ◽  
pp. 2636-2643 ◽  
Author(s):  
Cora Sternberg ◽  
Andrew Armstrong ◽  
Roberto Pili ◽  
Siobhan Ng ◽  
Robert Huddart ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Karnofsky Performance Status ◽  
Performance Status ◽  
Phase Iii ◽  
Castration Resistant Prostate Cancer ◽  
Double Blind ◽  
End Point ◽  
Castration Resistant ◽  
Phase Iii Study

Purpose Tasquinimod, a novel oral therapy targeting the tumor microenvironment, significantly improved progression-free survival (PFS) in a randomized, placebo-controlled phase II trial in men with metastatic castration-resistant prostate cancer (mCRPC). This phase III study was conducted to confirm the phase II results and to detect an overall survival (OS) benefit. Patients and Methods Men with chemotherapy-naïve mCRPC and evidence of bone metastases were assigned (2:1) to receive tasquinimod once per day or placebo until progression or toxicity. The primary end point was radiographic PFS (rPFS; time from random assignment to radiologic progression or death) per Prostate Cancer Working Group 2 criteria and RECIST 1.1. The study had 99.9% power to detect an rPFS hazard ratio (HR) of 0.6 with a two-sided alpha error of .05 and 80% power to detect a target HR of 0.8 for OS, the key secondary end point. Results In all, 1,245 patients were randomly assigned to either tasquinimod (n = 832) or placebo (n = 413) between March 2011 and December 2012 at 241 sites in 37 countries. Baseline characteristics were balanced between groups: median age, 71 years; Karnofsky performance status ≥ 90%, 77.3%; and visceral metastases, 21.1%. Estimated median rPFS by central review was 7.0 months (95% CI, 5.8 to 8.2 months) with tasquinimod and 4.4 months (95% CI, 3.5 to 5.5 months) with placebo (HR, 0.64; 95% CI, 0.54 to 0.75; P < .001). Median OS was 21.3 months (95% CI, 19.5 to 23.0 months) with tasquinimod and 24.0 months (95% CI, 21.4 to 26.9 months) with placebo (HR, 1.10; 95% CI, 0.94 to 1.28; P = .25). Grade ≥ 3 adverse events were more frequent with tasquinimod (42.8% v 33.6%), the most common being anemia, fatigue, and cancer pain. Conclusion In chemotherapy-naïve men with mCRPC, tasquinimod significantly improved rPFS compared with placebo. However, no OS benefit was observed.

Multinational, Double-Blind, Phase III Study of Prednisone and Either Satraplatin or Placebo in Patients With Castrate-Refractory Prostate Cancer Progressing After Prior Chemotherapy: The SPARC Trial

2009 ◽  
Vol 27 (32) ◽  
pp. 5431-5438 ◽  
Author(s):  
Cora N. Sternberg ◽  
Daniel P. Petrylak ◽  
Oliver Sartor ◽  
J. Alfred Witjes ◽  
Tomasz Demkow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Double Blind ◽  
Prior Chemotherapy ◽  
Prior Chemotherapy Regimen ◽  
Docetaxel Treatment ◽  
Risk Of Progression ◽  
Progression Of Disease ◽  
Phase Iii Study

Purpose This multinational, double-blind, randomized, placebo-controlled, phase III trial assessed the efficacy and tolerability of the oral platinum analog satraplatin in patients with metastatic castrate-refractory prostate cancer (CRPC) experiencing progression after one prior chemotherapy regimen. Patients and Methods Nine hundred fifty patients were randomly assigned (2:1) to receive oral satraplatin (n = 635) 80 mg/m2 on days 1 to 5 of a 35-day cycle and prednisone 5 mg twice daily or placebo (n = 315) and prednisone 5 mg twice daily. Primary end points were progression-free survival and overall survival (OS). The secondary end point was time to pain progression (TPP). Results A 33% reduction (hazard ratio [HR] = 0.67; 95% CI, 0.57 to 0.77; P < .001) was observed in the risk of progression or death with satraplatin versus placebo. This effect was maintained irrespective of prior docetaxel treatment. No difference in OS was seen between the satraplatin and placebo arms (HR = 0.98; 95% CI, 0.84 to 1.15; P = .80). Compared with placebo, satraplatin significantly reduced TPP (HR = 0.64; 95% CI, 0.51 to 0.79; P < .001). Satraplatin was generally well tolerated, although myelosuppression and GI disorders occurred more frequently with satraplatin. Conclusion Oral satraplatin delayed progression of disease and pain in patients with metastatic CRPC experiencing progression after initial chemotherapy but did not provide a significant OS benefit. Satraplatin was generally well tolerated. These results suggest activity for satraplatin in patients with CRPC who experience progression after initial chemotherapy.

Efficacy of CAB therapy in stage C prostate cancer: Exploratory analyses based on results of a double-blind, randomized, placebo-controlled phase III study of bicalutamide

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5154-5154 ◽  
Author(s):  
H. Akaza ◽  
Y. Arai ◽  
H. Kanetake ◽  
S. Naito ◽  
M. Usami
Keyword(s):  
Prostate Cancer ◽  
Locally Advanced ◽  
Phase Iii ◽  
Double Blind ◽  
Term Survival ◽  
Class Time ◽  
Phase Iii Study ◽  
Better Than ◽  
Observation Period

5154 Background: Although the efficacy of CAB in advanced prostate cancer (PC) has been demonstrated by the PCTCG and others, more evidence is required in locally advanced (Stage C) PC. The results of a Japanese P III study of bicalutamide in Stage C/D PC suggested the efficacy of CAB was better than monotherapy. When time to progression (TTP) was evaluated in Stage C and D separately, CAB had significant benefits in both stages and results in stage D were consistent with PCTCG data. Thus, this exploratory analysis was conducted to evaluate more thoroughly the efficacy of CAB in Stage C. Methods: 205 untreated PC patients with Stage C/D were randomized to CAB (goserelin 3.6 mg/4 weeks or leuprorelin 3.75 mg/4 weeks + bicalutamide 80 mg/day) or LHRHa monotherapy (same LHRHa + placebo). Among these patients, 99 had Stage C (52/47 on CAB/monotherapy). The median of the following parameters were calculated, and log-rank tests performed: TTP in all Stage C patients; TTP in Stage C patients by age, PSA value at diagnosis, and histopathological class; time to PSA normalization when normal level was defined as =4, =1 and =0.2 ng/mL. Results: The median observation period in Stage C patients was 144 weeks. The median TTPs by each parameter in Stage C are shown below. The median times to PSA normalization on CAB and monotherapy were 7 and 16 weeks (p<0.01), 8 and 93 weeks (p<0.01) and 20 weeks and NR (p<0.01) with normal values defined as =4, =1 and =0.2 ng/mL, respectively. Conclusions: These results suggest that CAB with bicalutamide possesses superior efficacy to LHRHa monotherapy in Stage C regardless of age, PSA value at diagnosis, or degree of tumor differentiation. It is suggested that CAB in Stage C could decrease PSA to lower levels in a shorter period than with LHRHa monotherapy. The study is ongoing to assess long term survival outcome. [Table: see text] No significant financial relationships to disclose.

Lume-lung 2: A multicenter, randomized, double-blind, phase III study of nintedanib plus pemetrexed versus placebo plus pemetrexed in patients with advanced nonsquamous non-small cell lung cancer (NSCLC) after failure of first-line chemotherapy.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 8034-8034 ◽  
Author(s):  
Nasser H. Hanna ◽  
Rolf Kaiser ◽  
Richard N. Sullivan ◽  
Osvaldo Rudy Aren ◽  
Myung-Ju Ahn ◽  
...  
Keyword(s):  
Predictive Marker ◽  
Phase Iii ◽  
Double Blind ◽  
Safety Issues ◽  
Phase Iii Study ◽  
Previously Treated ◽  
Ecog Ps ◽  
Unacceptable Toxicity ◽  
Clinical Trial Information

8034 Background: Nintedanib (N) is an oral inhibitor of VEGFR, FGFR, and PDGFR. This global phase 3 study investigated the safety and efficacy of N + pemetrexed (PEM) vs placebo (P) + PEM in patients (pts) with advanced, non-squamous NSCLC previously treated with chemotherapy. Methods: Pts were randomized 1:1 to N 200 mg po bid + PEM 500 mg/m2 iv q21d (n=353, Arm A) or P + PEM (n=360, Arm B). Continuation until PD or unacceptable toxicity with N, P, PEM, or a combination was permitted. 1° endpoint was centrally reviewed PFS. The null hypothesis was tested on the ITT population after 394 events had occurred (two sided α=5%). 2° endpoints included OS, investigator-assessed PFS, response rate (RR), safety, and QoL. Results: Baseline pt characteristics were balanced between Arm A vs B (median age 59 y, female 45–42%, ECOG PS 1 62-61%, adenocarcinoma 95–93%, prior bevacizumab 8%). Based on a planned DMC futility analysis of investigator-assessed PFS, enrolment was halted after randomizing 713/1300 planned pts (no safety issues identified). Ongoing pts were unblinded and follow-up continued per protocol. Subsequent ITT analysis of the 1° endpoint (centrally reviewed PFS) favored Arm A vs B (median 4.4 vs 3.6 mo, HR 0.83 [95% CI: 0.7–0.99], p=0.04). Disease control was also significantly improved in N-treated pts (61 vs 53%, odds ratio 1.37, p=0.039). No difference in OS (HR 1.03) or RR (9%) was found. Exploratory analyses identified time since start of 1st-line therapy as a predictive marker of improved outcome with N + PEM (ASCO 2013). There was no increase in SAEs or G5 AEs with N + PEM. Addition of N to PEM resulted in a higher incidence of ≥G3 elevated ALT (23 vs 7%), elevated AST (12 vs 2%), and diarrhea (3 vs 1%), but no difference in ≥G3 hypertension, bleeding, thrombosis, mucositis, or neuropathy. Conclusions: The 1° endpoint was met even though the study was stopped prematurely. Treatment with N + PEM significantly improved centrally reviewed PFS vs P + PEM in pts with advanced non-squamous NSCLC previously treated with chemotherapy, and had a manageable safety profile. Clinical trial information: NCT00806819.

Phase III results of adjuvant radiotherapy (RT) versus wait-and-see (WS) in patients with pT3 prostate cancer following radical prostatectomy (RP)(ARO 96-02/AUO AP 09/95): Ten years follow-up.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 4-4 ◽  
Author(s):  
Thomas Wiegel ◽  
Dirk Bottke ◽  
Detlef Bartkowiak ◽  
Claudia Bronner ◽  
Ursula Steiner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Progressive Disease ◽  
Hormonal Treatment ◽  
Late Toxicity ◽  
Phase Iii ◽  
Phase Iii Study ◽  
Grade 3 ◽  
Intent To Treat

4 Background: Adjuvant RT for pT3 R1 or R0 patients (pts.) after RP remains controversial. The EORTC-phase-III- study suggested a 20% better biochemical control (bNED) after 10 years for RT but no survival advantage. In contrast, the SWOG trial stated not only a gain in bNED but also an improved metastasis free and overall survival after 12 years follow-up. Now, 10-years results from the ARO 96-02 study are available, which are based on the most precisely defined cohort among the three trials. Methods: 385 men with prostate cancer were randomized to either 60 Gy RT (arm A; n=193) or WS (arm B; n=192) before achieving an undetectable PSA. Pts. were stratified for Gleason-score, margin status, neoadjuvant hormonal treatment and stage (pT3a+b vs. c). When the undetectable PSA-level after RP was not achieved, progressive disease was stated and the pts. left arm A/B. Data analysis was by intent-to-treat (ITT). PSA-progression for pts. with undetectable post-RP PSA was defined as two consecutive increasing PSA. The primary endpoint was bNED. The study was powered to demonstrate a 15% increase in bNED for RT. Results: 78 pts. (20%) did not achieve an undetectable PSA and were stated as progressive disease (arm A: 45 pts., arm B: 33 pts.). Additionally, 34 pts. (23%) from the RT-arm did not receive RT. Therefore, 114 pts. had RT (arm A) and 159 pts. WS (arm B). Median follow up was 111.3 months for arm A and 113.3 months for arm B . bNED at 10 years increased to 56% for arm A (RT) compared with 35% for arm B (WS) (hazard ratio= 0.51; p = 0.00002. Out of 307 ITT pts., 15 died from prostate cancer, 23 for other and 5 for unknown reasons. There was no significant profit from ART regarding the endpoints metastasis-free survival (p=0.56) or overall survival (p=0.59). Worst late side effects to the rectum were two grade 2 cases after ART. Grade ≥2 bladder toxicity occurred in 4 out of 148 ITT pts. No grade 4 events were reported. Conclusions: With only one grade 3 case of late toxicity, ART was safe in pT3 prostate cancer. At 10 years median follow up, it reduced the risk of bNED by 49%. The study was not powered to detect differences in OS. Clinical trial information: ARO 96-02/AUO AP 09/95.

scholarly journals Subcutaneous tanezumab for osteoarthritis of the hip or knee: efficacy and safety results from a 24-week randomised phase III study with a 24-week follow-up period

2020 ◽  
Vol 79 (6) ◽  
pp. 800-810 ◽  
Author(s):  
Francis Berenbaum ◽  
Francisco J Blanco ◽  
Ali Guermazi ◽  
Kenji Miki ◽  
Takaharu Yamabe ◽  
...  
Keyword(s):  
Physical Function ◽  
Standard Of Care ◽  
Phase Iii ◽  
Womac Pain ◽  
Double Blind ◽  
End Points ◽  
Factor Inhibitor ◽  
Registration Number ◽  
Phase Iii Study

ObjectiveTanezumab, a nerve growth factor inhibitor, was investigated for osteoarthritis (OA) of the hip or knee in a study with 24-week treatment and 24-week safety follow-up.MethodsThis double-blind, randomised, phase III study enrolled adults in Europe and Japan with moderate-to-severe OA who had not responded to or could not tolerate standard-of-care analgesics. Patients were randomised to tanezumab 2.5 mg or 5 mg subcutaneously or matching placebo every 8 weeks (three doses). Co-primary end points were change from baseline to week 24 in Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) Pain and Physical Function, and Patient’s Global Assessment of OA (PGA-OA). Joint safety and neurological assessments continued throughout the 48-week study.ResultsFrom March 2016 to December 2017, 849 patients were randomised and evaluated (placebo n=282, tanezumab 2.5 mg n=283, tanezumab 5 mg n=284). At week 24, there was a statistically significant improvement from baseline for tanezumab 5 mg compared with placebo for WOMAC Pain (least squares mean difference±SE –0.62±0.18, p=0.0006), WOMAC Physical Function (–0.71±0.17, p<0.0001) and PGA-OA (–0.19±0.07, p=0.0051). For tanezumab 2.5 mg, there was a statistically significant improvement in WOMAC Pain and Physical Function, but not PGA-OA. Rapidly progressive osteoarthritis (RPOA) was observed in 1.4% (4/283) and 2.8% (8/284) of patients in the tanezumab 2.5 mg and tanezumab 5 mg groups, respectively and none receiving placebo. Total joint replacements (TJRs) were similarly distributed across all three treatment groups (6.7%–7.8%). Tanezumab-treated patients experienced more paraesthesia (5 mg) and hypoaesthesia (both doses) than placebo.ConclusionTanezumab 5 mg statistically significantly improved pain, physical function and PGA-OA, but tanezumab 2.5 mg only achieved two co-primary end points. RPOA occurred more frequently with tanezumab 5 mg than tanezumab 2.5 mg. TJRs were similarly distributed across all three groups.Trial registration numberNCT02709486.

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