GLORIA

GEOMAR Library Ocean Research Information Access

X

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Online Resource
    Online Resource
    Clinical study of VERU-111, an oral cytoskeletal disruptor, in metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 6_suppl ( 2021-02-20), p. 131-131
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 6_suppl ( 2021-02-20), p. 131-131
    Abstract: 131 Background: VERU-111 is an oral, cytoskeletal disruptor that crosslinks α & ß tubulin and inhibits microtubule polymerization with no affinity for multidrug resistance proteins. A Phase 1b/2 clinical study has been conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with progressive mCRPC resistant to androgen receptor targeting agent (ARTA). Methods: In the Phase 1b portion of the study, a 3+3 design with escalating oral dosing of 4.5 - 81 mg (7 days on drug/14 days off per 21 day cycle) was utilized. After no dose limiting toxicity was observed, the dose was increased in the next cohort. The schedule was also expanded in those completing the 7 days on/14 days off cycle to continuous dosing/cycle. The recommended Phase 2 study dose is 63 mg daily and the trial is fully enrolled with 40 taxane-naiive men with mCRPC that have failed at least one ARTA. Results: In the Phase 1 portion of the study, 30 taxane-naïve mCRPC men with a median age of 76 (61-92) were enrolled. 8 received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases. The MTD of VERU-111 is 72mg (3 /11 men had Grade 3 diarrhea). No Grade 3 diarrhea was observed at doses 〈 72 mg per day. At doses 〈 72mg/d, the most common AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. In the Phase 1b, antitumor activity was assessed by PSA and bone/CT scans in men that were treated for ≥ 4 continuous 21-day cycles. 6/10 (60%) had PSA declines: 4 (40%) men had ≥ 30% and 2(20%) ≥ 50% declines compared to their 21 day cycle baseline. Based on PCWG3/RECIST 1.1 criteria, objective tumor responses were seen in 2 men (soft tissue and bone). Median duration of response is 11 months (6-18+ months). In the Phase 2 portion of the study, 49% had bone only metastases, 54% have bone only metastases, 11% have nodal disease, 32% had mixed bone and nodal disease and 3% had visceral disease. This portion of the study is ongoing and results will be reported. 9/29 (31%) had previously abiraterone, 10/29 (34%)( enzalutmide, 7/29 (24%) both enzalutmide and abiraterone and 4/29 (14%) apalutamide. Conclusions: Based upon this Phase 1b/2 clinical trial, oral VERU-111 has a favorable safety profile allowing for chronic administration and significant and durable antitumor activity. The daily dose of 63mg is being tested in the fully enrolled Phase 2 portion. Oral administration, safe long-term treatment and evidence of antitumor activity highlight a potential prominent role of VERU 111 for the treatment of men with mCRPC who failed an androgen receptor targeting agent. Clinical trial information: NCT03752099.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.6_suppl.131
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 2
    Online Resource
    Online Resource
    The role of sabizabulin in phase 1b/2 clinical trials of men with metastatic castration-resistant prostate cancer who progressed on androgen receptor-targeting agents.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 110-110
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 110-110
    Abstract: 110 Background: Sabizabulin is a novel oral cytoskeleton disruptor being developed for use in metastatic castration resistant prostate cancer (mCRPC). A phase 1b/2 clinical study was conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC resistant to androgen receptor targeting agents (ARTAs). Methods: The phase 1b portion of the study in 39 men utilized escalating and expanding dose and duration. The phase 2 portion studied 41 men with mCRPC at the recommended phase 2 dose (RP2D) of 63 mg daily. Based upon the phase 1b/2 data, sabizabulin appears to have both cytotoxic and cytostatic activity. A analysis was conducted evaluating the best clinical response (BCR) defined as either an objective response assessed by PCWG3 criteria and/or stable disease defined as ≥5 cycles (≥15 weeks) of continuous treatment. Results: Of the combined 80 patients in the phase 1b/2 portions of the study, the BCR was 37.5% (30/80) and 5 of the responders remain on study with the longest being treated for more than 30 months. Of the patients with measurable disease at study entry, the BCR was 59% (17/29). Prior to study entry, 11/30 (37%) of those with a BCR had previously been treated with and subsequently progressed on a minimum of 2 ARTAs. The remaining 19/30 (63%) had progressed on a single ARTA agent. 11 (37%) were previously treated with enzalutamide or apalutamide and 8 (27%) with abiraterone as single agents. 8 (27%) received enzalutamide and abiraterone and 3 (10%) patients received more than two ARTAs. As described previously, the safety profile continues to be favorable with no clinically relevant neutropenia or neurotoxicity. Conclusions: In this analysis, sabizabulin has demonstrated not only cytotoxic, but also significant cytostatic activity with similar responses in men that have progressed on a single or multiple ARTA agents. Sabizabulin is a novel agent with the potential provide men with mCRPC a well-tolerated chronic treatment cytostatic option after progressing on an ARTA and is being tested in the open phase 3 VERACITY trial. Clinical trial information: NCT03752099.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.110
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 3
    Online Resource
    Online Resource
    VERU-111, an oral cytoskeleton disruptor, to treat men with metastatic castration-resistant prostate cancer (mCRPC) who failed an androgen receptor targeting agent.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. 5056-5056
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. 5056-5056
    Abstract: 5056 Background: VERU-111 is an oral cytoskeletal disruptor that disrupts microtubules supporting the cytoskeleton and has no affinity for multidrug resistance proteins. A phase 1b/2 clinical study has been conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC also resistant to androgen receptor targeting agents. Methods: In the phase 1b component of the study, a 3+3 design with escalating oral dosing of 4.5 mg to 81 mg (7 days on drug/14 days off per 21-day cycle) was utilized. The schedule was also expanded to continuous dosing/cycle. The phase 2 portion utilized 63 mg daily dosing to evaluate efficacy in approximately 40 taxane-naïve men with mCRPC that have failed at least one androgen receptor targeting agent. Results: In the phase 1b portion of the study, 30 taxane-naïve men with mCRPC and a median age of 76 (61-92) were enrolled. 8 had received prior enzalutamide, 12 abiraterone and 10 both. 8 men had bone mets, 5 lymph node, 5 mixed and 1 had soft tissue metastases at study entry. The MTD of VERU-111 is 72mg (3/11 men had grade 3 diarrhea) and the recommended phase 2 dose is 63mg. Grade 3 diarrhea was not observed at doses ≤ 63mg per day and the most common non-dose limiting AEs were mild to moderate nausea, vomiting, diarrhea, and fatigue, with no observed neurotoxicity or neutropenia. Efficacy was assessed by PSA and bone/CT scans. In men treated for ≥ 4 continuous 21-day cycles, 6/10 (60%) had PSA declines, 4(40%) men had ≥ 30% declines and 2(20%) ≥ 50% declines compared to their 21-day cycle baseline PSA. Median PFS is currently 12 months (6-23+ months) with 3 patients continuing on study, 2 of which have been on study for approximately 2 years. In patients receiving at least a single dose of ≥ 63 mg daily (n=19), objective tumor responses were seen in 3 men (16%). The median rPFS in these patients is currently 12.4 months. In the phase 2 portion of the study, 55% of the patients had bone only metastases, 11% had nodal only, 32% had mixed bone and nodal disease and 3% had visceral disease at study entry. 6/32 (19%) were previously treated with abiraterone alone, 12/32 (38%) with enzalutamide alone, and 14/32 (44%) had abiraterone in combination with enzalutamide, proxalutamide or apalutamide. The phase 2 portion of the study is ongoing and objective tumor responses have been observed including a CR and PRs and PSA decreases 〉 50%. Patients have been on study as long as 9 months. Conclusions: This phase 1b/2 clinical trial, demonstrates that oral daily dosing of VERU-111 has a favorable safety profile and that chronic dosing is feasible. The recommended phase 2 dose of 63mg daily has significant durable antitumor activity. These data support a potential prominent role of VERU 111 for the treatment of men with mCRPC who previously failed an androgen receptor targeting agent and prior to the administration of intravenous chemotherapy. Clinical trial information: NCT03752099.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.5056
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 4
    Online Resource
    Online Resource
    Final analysis of the phase 1b/2 study of sabizabulin in men with metastatic castration-resistant prostate cancer who progressed on an androgen receptor targeting agent.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 16_suppl ( 2022-06-01), p. 5049-5049
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 16_suppl ( 2022-06-01), p. 5049-5049
    Abstract: 5049 Background: Sabizabulin is a novel oral cytoskeleton disruptor being developed for use in metastatic castration resistant prostate cancer (mCRPC). A Phase 1b/2 clinical study was conducted to establish the maximum tolerated dose (MTD) and evaluate the preliminary efficacy in men with mCRPC resistant to androgen receptor targeting agents. Methods: The Phase 1b portion of the study in 39 men utilized escalating and expanding dose and duration. The Phase 2 portion studied 41 men with mCRPC at the recommended Phase 2 dose of 63 mg daily. Efficacy was assessed by bone/CT scans. A final analysis of the safety and efficacy data including the primary endpoint, the median progression-free survival was conducted. Results: Although the MTD was not reached in the Phase 1b, the recommended Phase 2 dose was set at 63 mg/day to maximize GI tolerability. The most common adverse events ( 〉 10% frequency) at the 63 mg oral daily dosing (combined Phase 1b/2 data) were predominantly Grade 1-2. Grade ³3 events included diarrhea (7.4%), fatigue (5.6%) and ALT/AST elevations (5.6% and 3.7%, respectively). Neurotoxicity and neutropenia were not observed. Preliminary efficacy data in patients treated with ≥1 continuous cycle (21 days) of 63 mg or higher (n = 55) included an objective response rate of 6/29 (20.7%) in patients with measurable disease (1 complete, 5 partial). 14/48 (29.2%) of the patients had PSA declines. The Kaplan-Meier median radiographic progression-free survival was estimated to be 11.4 months (95% C.I. 29.63-65.79) (n = 55). Durable responses lasting 〉 2.75 years were observed with 14.5% (8/55) demonstrating a response greater than 12 months. Conclusions: This clinical trial demonstrated that chronic oral daily dosing of sabizabulin has a favorable safety profile with significant preliminary cytotoxic and cytostatic antitumor activity. These data support the ongoing Phase 3 VERACITY trial of sabizabulin in men with mCRPC who have progressed on an androgen receptor targeting agent. Clinical trial information: NCT03752099.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.16_suppl.5049
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 5
    Online Resource
    Online Resource
    Blood biomarkers and association with clinical outcomes in metastatic castration-resistant prostate cancer (mCRPC): prespecified longitudinal analysis from the ACIS study of apalutamide (APA) or placebo combined with abiraterone acetate plus prednisone (AAP).
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 142-142
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 142-142
    Abstract: 142 Background: In ACIS, APA + AAP improved radiographic progression-free survival in mCRPC vs AAP; difference in overall survival (OS) was not statistically significant. We report a prespecified analysis of androgen receptor (AR) or non-AR genomic/transcriptional aberrations, known to be associated with poor prognosis, and their associations with OS in patients (pts) with mCRPC. Methods: Circulating tumor (ct)DNA and aberrations in 17 PC-relevant genes were assessed using next-generation sequencing at baseline (BL; n = 197) and at end of study treatment (EOST; n = 140) (biomarker population). ctDNA was summarized qualitatively; genomic aberrations were normalized by ctDNA detection. AR splice variant version 7 (ARv7) was detected by quantitative RT-PCR. Cox proportional hazards model assessed association of OS with biomarkers in univariate/multivariate analyses overall and in pts receiving subsequent treatment (tx). Results: BL characteristics of biomarker and total study populations were similar. From BL to EOST: ctDNA detection did not differ (123/196 [63%] to 92/140 [66%] , p=0.6); significant increases occurred in ARv7, AR mutations, and any AR aberration (Table). Prevalence of aberrations in PI3K and homologous recombination repair (HRR) pathways did not change from BL to EOST (40/123 [33%] to 34/92 [37%] , p=0.5 and 18/123 [15%] to 14/92 [15%] , p 〉 0.9, respectively). Worse OS was associated with ctDNA detection or HRR pathway inactivation at BL (HR, 2.5 or 2.2; all p 〈 0.001) or presence of ctDNA, ARv7, AR amplification or inactivation of TP53, RB1, or RB1/TP35 pathway at EOST (2.2, p 〈 0.001; 2.1, p 〈 0.001; 2.6, p 〈 0.001; 1.5, p 〈 0.05; 1.7, p 〈 0.05; 2.1, p 〈 0.001, respectively) in univariate analyses. EOST ARv7, AR amplification, and inactivation of RB1, TP53, or RB1/TP53 pathway was associated with worse OS in pts receiving subsequent tx. Detection of ctDNA and RB1 inactivation at BL and RB1/TP53 pathway inactivation at EOST was strongly associated with worse OS (2.1, 3.3, 2.9, respectively, all p 〈 0.01) in multivariate analyses. Conclusions: In ACIS, AAP or APA + AAP tx was associated with increased AR mutations and ARv7 expression. Detection of ctDNA and select AR/non-AR aberrations may predict poor survival in mCRPC. These markers may be used to improve tx selection following confirmation of their predictive value. Clinical trial information: NCT02257736. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.142
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 6
    Online Resource
    Online Resource
    Efficacy and safety of relugolix in black men with advanced prostate cancer: A subgroup analysis from the randomized, phase 3 HERO study versus leuprolide.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 105-105
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 105-105
    Abstract: 105 Background: Prostate cancer disproportionately impacts Black men, with a higher incidence and worse outcomes relative to other races (Siegel DA, MMWR Morb Mortal Wkly Rep. 2020;69:1473). In the international phase 3 HERO study, relugolix, the once-daily oral GnRH receptor antagonist, demonstrated superior continuous suppression of testosterone to castrate levels through week 48 compared to leuprolide (96.7% for relugolix vs. 88.8% of men receiving leuprolide; Shore N, NEJM 2020; 382:2187) in men with advanced prostate cancer (APC). To further characterize the results from this trial in black men a subgroup analysis of HERO was undertaken. Methods: HERO was a phase 3 randomized, open-label, study to evaluate relugolix vs. leuprolide in 930 treated men with APC. The subgroup analyzed included all Black men enrolled in the HERO study. Assessments analyzed included sustained testosterone suppression to castrate levels ( 〈 50 ng/dL) from day 29 through 48 weeks, early testosterone suppression to castrate levels (day 4 and day 15), PSA response ( 〉 50% decrease) at day 15 with confirmation at day 29, profound castration rate ( 〈 20 ng/dL) at day 15, and FSH level at the end of week 24. Results: Of the 930 men (relugolix: 622; leuprolide: 308) randomized and treated in HERO, 30 (4.8%) and 16 (5.2%) Black men were enrolled in the relugolix and leuprolide groups, respectively. Most men in this subgroup were from North America (82.6%) and ≤75 years old (89.1%), with a median age of 66 years. More Black men in the relugolix group had metastatic disease at study entry (30% vs. 25%), prior androgen deprivation therapy (13.3% vs. 6.3%), and prior prostatectomy (53.3% vs. 18.8%). Median PSA (12.8 vs. 16.0 ng/ml) and median testosterone levels (375.2 vs. 419.2 ng/dL) were lower at baseline for relugolix vs leuprolide. Of the Black men who received relugolix, 93.3% (95% confidence interval [CI], 75.9% to 98.3%) maintained castration through 48 weeks, as compared with 93.3% (95% CI, 61.3 to 99.0) of men receiving leuprolide (difference: 0% [95% CI, -15.5% to 15.5] ). Testosterone suppression to castrate levels at day 4 (53% vs 0%), castrate levels at day 15 (97% vs 13%), and profound castration rates on day 15 (67% vs 6%) were greater with relugolix vs leuprolide. PSA response at day 15 was 83.3% with relugolix and 6.3% with leuprolide. At the end of week 24, median FSH levels were 1.75 IU/L for relugolix and 3.72 IU/L for leuprolide. Incidence of all grade adverse events were 96.7% vs 87.5% and grade ≥3 adverse events were 16.7% vs 25.0% in the relugolix and leuprolide groups, respectively. Conclusions: In this HERO study subgroup analysis, relugolix was effective and generally well tolerated in a cohort of Black men, consistent with the relugolix results in the overall population. Given the limited size of the subgroup, additional research is warranted in this population. Clinical trial information: NCT03085095.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.105
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 7
    Online Resource
    Online Resource
    The FRAX score as a tool for estimating fracture risk in patients with advanced prostate cancer on androgen-deprivation therapy compared to the conventional T-score.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e16023-e16023
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e16023-e16023
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2014.32.15_suppl.e16023
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 8
    Online Resource
    Online Resource
    Accuracy of NaF PET/CT scan to detect bone metastases in CRPC.
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 4_suppl ( 2014-02-01), p. 186-186
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 4_suppl ( 2014-02-01), p. 186-186
    Abstract: 186 Background: The current standard for imaging Castration Resistant Prostate Cancer (CRPC) is aimed at detecting metastatic lesions to the bones. However, discovery, validation, and implementation of new imaging modalities have fallen considerably behind that of new therapies for this population. Recent studies have shown the NaF PET/CT Scans are significantly more sensitive and accurate in detecting bone lesions than conventionally used Bone Scintigraphy with Technetium-99 (Tc-99). This study conducted retrospective analysis to compare the competence of these two methods for identifying bone metastases. Methods: We conducted a charts review of 613 patients being currently treated with androgen deprivation therapy (ADT) and identified 55 patients who obtained a Na18F PET/CT Scan. Results: The median age was 75.5 years with a range of 52-89, for our cohort. Of these 55 patients, 5 (11.9%) were determined to have metastasis with Tc-99 Bone Scintigraphy alone while 27 (49.1%) were determined to have metastases with NaF Scan (p 〈 0.005). 8 (19%) patients had equivocal findings on Tc-99 Bone Scintigraphy. Therefore, for all of them we performed NaF scan to define a bone metastatic disease that demonstrated in 5 (62.5%) cases of these as having no bone involvement and 3(37.5%) as positive for bone lesions (Table). However, data of NaF scan also indicated 5(9%) patients as having equivocal findings for metastatic disease. Conclusions: According to our data, NaF is more sensitive for detecting bone lesions (11.9 vs. 49.1%). It was also able to delineating equivocal TC-99 Bone Scintigraphy findings, where it deemed 62.5% as negative and 37.5% as positive for bone lesions. NaF PET scan is a feasible option for CRPC for detecting bone metastases, early in disease progression. With coverage of this procedure by Medicare patients have more sensitive and specific tool for early diagnosis and monitoring of treatment of CRPC. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.4_suppl.186
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 9
    Online Resource
    Online Resource
    DAROL: DARolutamide ObservationaL study patients in nonmetastatic castration-resistant prostate cancer (nmCRPC) patients.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS5593-TPS5593
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. TPS5593-TPS5593
    Abstract: TPS5593 Background: Patients (pts) with prostate cancer treated with prolonged androgen deprivation therapy (ADT) will eventually develop castration-resistant disease. Treatment of pts with nmCRPC with darolutamide (DARO) delays the development of metastases, which are associated with cancer-related morbidity. DARO is a structurally unique oral androgen receptor inhibitor approved by the FDA for the treatment of nmCRPC, based on prolonged metastasis-free survival (MFS) compared with placebo (median 40.4 months vs.18.4 months, respectively) in the ARAMIS phase III clinical trial. DARO showed a similar incidence of adverse events (AEs) compared to ADT alone and has a low potential for drug-drug interactions. However, phase III clinical trials cannot fully reflect all the facets of real-world pts. Therefore, non-interventional studies in the real-world setting, such as DAROL, are able to provide additional insight into the patterns of use and real-world safety profile of recently approved drugs. Methods: (NCT04122976) will enrol participants in the US, Brazil, Japan, and the EU. Eligible pts include men with histologically confirmed nmCRPC aged ≥18 yrs, life expectancy ≥3 months, and initiated on DARO treatment as per investigators’ decision within 3 days prior to enrollment. DAROL opened for enrollment in December 2019 in the US with a projected enrollment of 1000 pts. The primary endpoint of DAROL is safety. Treatment-emergent AEs will be collected during the study. Secondary endpoints to measure clinical effectiveness are MFS, time to symptomatic skeletal event, time to prostate-specific antigen progression, survival rate, and duration of DARO therapy. Other endpoints include pt demographics and characteristics, and prior and subsequent therapy. The estimated primary completion date is December 30, 2024. Clinical trial information: NCT04122976 .
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.TPS5593
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
  • 10
    Online Resource
    Online Resource
    Second interim analysis (IA2) results from a phase II trial of TAK-385, an oral GnRH antagonist, in prostate cancer patients (pts).
    American Society of Clinical Oncology (ASCO) ; 2016
    In:  Journal of Clinical Oncology Vol. 34, No. 2_suppl ( 2016-01-10), p. 200-200
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 34, No. 2_suppl ( 2016-01-10), p. 200-200
    Abstract: 200 Background: Gonadotropin-releasing hormone (GnRH) antagonists achieve rapid decrease in testosterone (T) without transient T surge seen with GnRH agonists and thus may avoid clinical flare symptomatology. TAK-385 is an investigational, oral, non-peptide GnRH antagonist highly selective for the human GnRH receptor (IC 50 0.12 nM). We report IA2 results from a phase 2, randomized, open label, parallel group study of TAK-385 in pts with advanced prostate cancer (NCT02083185). Methods: Pts aged ≥ 18 yrs with histologically confirmed prostate cancer, baseline T 〉 150 ng/dL and prostate-specific antigen (PSA) 〉 2 ng/mL, who were candidates for first-line androgen deprivation therapy, were randomized to receive oral TAK-385, 80 or 120 mg, once daily (QD) or leuprorelin (LEU) 22.5 mg subcutaneously every 12 wks, for 48 wks. The primary endpoint was effective castration rate of TAK-385 (T 〈 50 ng/dL) from wk 5–24. Secondary endpoints included: safety, pharmacokinetics (PK), and PSA. Results: At data cut-off, 75 pts had received TAK-385 (39 at 80 mg, 36 at 120 mg QD); 20 pts received LEU. Median age was 73 yrs with TAK-385 and 68.5 yrs with LEU; median treatment duration was 35.1 wks and 37.8 wks. After 3 days/4 wks/24 wks of treatment, median T was 36.9/10.6/8.9 ng/dL with TAK385 vs 648.1/13.0/11.5 ng/dL with LEU. T 〈 50 ng/dL was sustained over 5–24 wks in 92% vs 95% of pts (TAK-385 vs LEU). After 24 wks, PSA was reduced by 97.3% to a median of 0.1 ng/mL with TAK-385 vs 92.4% to 0.2 ng/mL with LEU. All-grade adverse events occurred in 91% vs 95% of pts (TAK-385 vs LEU); the most common were hot flush (59/60%), fatigue (21/15%), elevated alanine aminotransferase (9/10%), nasopharyngitis (8/5%), and elevated aspartate aminotransferase (5/10%). Initial analysis of pooled phase 1/2 data showed similar PK in the phase 2 pts and in previously studied healthy men, with dose-proportional plasma trough levels over 〉 6 mos. Conclusions: At IA2, the efficacy of TAK-385 was consistent with the GnRH antagonist mechanism of action and the safety profile was good. TAK-385 rapidly reduced T and sustained castration ( 〈 50 ng/dL) over 24 wks. Further investigation of TAK-385, as an option to injectable GnRH therapies, is warranted. Clinical trial information: NCT02083185.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2016.34.2_suppl.200
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2016
    detail.hit.zdb_id: 2005181-5
    Location Call Number Limitation Availability
    BibTip Others were also interested in ...
    Online Resource
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...