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  • 11
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    Online Resource
    The fluciclovine (FACBC) PET/CT site-directed therapy of oligometastatic prostate cancer (Flu-BLAST-PC) trial.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS5099-TPS5099
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 15_suppl ( 2021-05-20), p. TPS5099-TPS5099
    Abstract: TPS5099 Background: Patients with biochemical recurrence (BCR) after local definitive therapy for prostate cancer (PC) represent the largest group of patients alive with PC in the United States. For patients with BCR after both radical prostatectomy and radiation, no further definitive treatment options currently exist as standard of care. FACBC PET/CT is a next-generation imaging modality approved in 2016 for suspected PC recurrence based on elevated PSA levels following prior treatment. FACBC PET/CT allows for earlier detection at lower PSA levels of oligometastatic PC in patients who would otherwise be considered as having micro-metastatic disease. FACBC PET/CT may provide potential targets for site-directed therapy; however, it is unknown whether this approach leads to improvement in clinically relevant outcomes. Methods: Flu-BLAST-PC (ClinicalTrials.gov Identifier: NCT0417543) is a prospective, interventional study enrolling men with PC and BCR who have previously undergone both radical prostatectomy and adjuvant or salvage radiation to the prostatic fossa, with PSA ≥0.5 to 〈 10 ng/mL, PSA doubling time 〉 3 to 〈 18 months, and no radiographically detectable metastases by conventional CT and bone scan imaging. Enrolled patients undergo FACBC PET/CT imaging, and those with no PC metastases detected (Group 1) undergo observation with repeat FACBC PET/CT performed at PSA thresholds of 〉 2 and 〉 5 ng/mL, with eligibility for the trial ending at PSA ≥10 ng/mL if FACBC PET/CT remains negative. Those with 1-3 PC regions (defined as radiation fields) detected on FACBC PET/CT (Group 2) undergo site-directed therapy with surgery (e.g. lymphadenectomy) and/or radiation, as well as six months of systemic treatment with androgen deprivation therapy (ADT) and abiraterone acetate with prednisone. Patients with ≥4 PC regions detected on FACBC PET/CT (Group 3) undergo six months of ADT and abiraterone acetate with prednisone without any site-directed therapy. Patients initially in Group 1 who subsequently have PC metastases detected on repeat FACBC PET/CT imaging per protocol join Group 2 or Group 3 based on the number of PC regions involved. Given the long anticipated survival of patients with PC and BCR, the primary endpoint of the study is undetectable PSA ( 〈 0.2 ng/mL) rate in Group 2 at two years beyond study treatment, with secondary endpoints including the same outcome measure for Group 3, undetectable PSA rate two years after testosterone recovery from ADT in Groups 2 and 3, time to re-initiation of ADT, overall survival, and safety and tolerability. Assuming a null hypothesis of 15% undetectable PSA rate for patients with BCR two years after completing ADT and alternative hypothesis of improvement to 40% in Group 2, planned enrollment is 65 patients in Group 2. This will provide 90% power at the two-sided significance level of 0.05. Five patients have enrolled to date. Clinical trial information: NCT0417543.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.15_suppl.TPS5099
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 12
    Online Resource
    Online Resource
    Sarcomatoid urothelial carcinoma (SUC): A single-institution experience of oncologic outcomes and recurrence patterns.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 6_suppl ( 2020-02-20), p. 465-465
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 6_suppl ( 2020-02-20), p. 465-465
    Abstract: 465 Background: SUC is a rare histology with aggressive behavior. We evaluated outcomes and recurrence patterns of patients (pts) with SUC, in comparison with conventional urothelial carcinoma (CUC). Methods: We retrospectively assessed our radical cystectomy (RC) database to identify pts with cT2-4 SUC (any %) or CUC, at RC or transurethral resection specimens. Clinicopathologic/treatment data were captured and compared with t and χ 2 tests, as appropriate. Overall survival (OS; diagnosis to death) and recurrence-free survival (RFS; RC to recurrence or death) were estimated (KM method). Significant factors in univariable (UVA) Cox regression for OS were included in multivariable analysis (MVA). Results: We identified 38 consecutive pts with cT2-4 SUC and 287 with CUC (2003-2018); 17 (45%) and 162 (56%) received neoadjuvant chemotherapy (NAC). The primary non-mesenchymal component was urothelial in all SUC cases. SUC had higher rates of pT3/4 (66% vs. 35%, p 〈 .001) but comparable rates of pN+ disease (26% vs. 20%, p = .38). Complete response (ypT0N0) after NAC was lower for SUC (6% vs. 35%, p = .02). Median follow-up was 73.6 months (95%CI 62.6 – 84.7). Median RFS and OS was inferior among pts with SUC (9.4 vs 109.8 months, p 〈 .001, 19.7 vs. 130.4 months, p 〈 .001 respectively). On MVA, SUC was independently associated with worse OS ( Table). Of 17 (45%) pts with SUC who recurred post-RC, 5 presented with abdomino-pelvic cystic masses, with an average time to recurrence 〈 5 months. Conclusions: SUC was associated with high rates of extravesical spread at RC and worse NAC response, RFS and OS, vs. CUC. Development of abdomino-pelvic fluid collections should raise suspicion of recurrence among pts with this histology. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.6_suppl.465
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 13
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    Results of a multicenter phase I/II trial of abiraterone acetate plus BEZ235 in metastatic, castration-resistant prostate cancer (mCRPC).
    American Society of Clinical Oncology (ASCO) ; 2014
    In:  Journal of Clinical Oncology Vol. 32, No. 15_suppl ( 2014-05-20), p. e16042-e16042
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 32, No. 15_suppl ( 2014-05-20), p. e16042-e16042
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2014.32.15_suppl.e16042
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2014
    detail.hit.zdb_id: 2005181-5
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  • 14
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    Molecular subtype variation within metastasis of urothelial carcinoma.
    American Society of Clinical Oncology (ASCO) ; 2021
    In:  Journal of Clinical Oncology Vol. 39, No. 6_suppl ( 2021-02-20), p. 471-471
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 39, No. 6_suppl ( 2021-02-20), p. 471-471
    Abstract: 471 Background: Molecular subtyping of cancer based on gene expression is a new prognostic tool with potential to guide treatment in the future. Urothelial carcinoma is one such cancer for which numerous molecular subtyping systems have been developed, but the diversity of these systems has hindered their clinical application. Recently, a consensus classification system was derived from six independent systems, defining six molecular classes with distinct oncogenic mechanisms and mutations (Kamoun A, et al. 2020). Considering the high heterogeneity in urothelial carcinoma, we hypothesized that molecular subtype variation may occur between primary and metastatic samples. We further evaluated whether variation in subtype was associated with any unique patient characteristics. Methods: As part of the University of Washington Bladder Cancer Rapid Autopsy Program (BCRAP), primary and metastatic tumor tissue samples were acquired from 14 deceased patients with urothelial carcinoma within 6 hours of death. Patient history was collected and deidentified for analysis. RNA exome sequencing was used for assigning molecular subtype for each of the 61 tumor samples, using the consensus and six comprising systems. Results: Molecular subtype variation within metastatic tumors according to any classification system was detected in 8 out of 14 patients, independent of histologic morphologies. Amongst the patients with variation, on average 2.1 out of 7 classification systems identified a major difference in subtype between sites. Patients with variation (mean age 70 years (SD 7 years)) were older than those without variation (mean age 59 years (SD 11 years), P = 0.04). Furthermore, patients with variation tended to have decreased survival from diagnosis and received less chemotherapy, although these were not statistically significant (p 〉 0.05). Conclusions: Molecular subtype variation within metastasis is relatively common amongst BCRAP patients with urothelial carcinoma. Older patients are more likely to have variation, possibly due to a higher tumor mutation burden. Potential variation must be taken into account when considering prognosis and developing a recommended drug regimen specific to molecular subtypes.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2021.39.6_suppl.471
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2021
    detail.hit.zdb_id: 2005181-5
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  • 15
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    Prospective evaluation of a comprehensive geriatric assessment (CGA) in multidisciplinary bladder cancer care: Feasibility and impact on decisional conflict.
    American Society of Clinical Oncology (ASCO) ; 2022
    In:  Journal of Clinical Oncology Vol. 40, No. 6_suppl ( 2022-02-20), p. 479-479
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 40, No. 6_suppl ( 2022-02-20), p. 479-479
    Abstract: 479 Background: Commonly utilized risk stratification tools demonstrate inconsistent associations with salient clinical outcomes in bladder cancer leading to a disproportionate reliance on providers’ subjective impression of a patient’s fitness for therapy. Current guidelines advocate for use of a CGA to quantify vulnerabilities in older ( 〉 65 years) patients before treatment selection. Our objective was to prospectively evaluate CGA in our Bladder Cancer Multidisciplinary Clinic (BCMC). We hypothesized that CGA implementation would be feasible and that discussion of the results during shared decision-making would be associated with reduced patient-reported decisional conflict. Methods: Patients seen in BCMC were prospectively enrolled from 6/1/20 to 7/20/21. In the first 3 months, participants underwent non-standardized risk stratification (“Routine cohort”, N = 27). Between 9/1/20 and 7/20/21, participants completed a CGA incorporating validated assessments of frailty, functional status, multimorbidity, nutrition, cognition, and mental health (“CGA cohort”, N = 67). Results were shared with patients during BCMC visits. All patients and providers (three physicians per clinic from: Uro-Oncology, Medical Oncology, and Radiation Oncology) completed a follow-up survey including the Decisional Conflict Scale (DCS). Time required to complete the CGA, completion rates, and patient-reported burden were assessed. Concordance of patient- and provider-reported decisional conflict was compared between Routine and CGA cohorts. Results: Of 138 eligible patients, 94 patients were successfully enrolled (68%) with median age of 72 years, ECOG PS ≥3 in 13%, and Charlson Comorbidity Index ≥3 in 18%, of whom 18% were women. Most patients had pT2 bladder cancer (87%; cN+ and M1 in 23.4% and 9.6%, respectively). CGA component completion rates were 79-100%. Survey response rates were high (patients: 77%, providers: 86%), and most (86%) patients felt that the CGA was, at most, minimally burdensome. Vulnerabilities detected across CGA domains triggered relevant referrals. Patient-reported median (IQR) DCS scores were numerically higher (e.g. greater decisional conflict) for the CGA cohort: (27 [14-33] vs 16 [2-30] for Routine patients, p = 0.28). Provider- and provider reported DCS score was correlated in the CGA (p = 0.04), but not the Routine cohort (p = 0.07). Conclusions: We prospectively evaluated use of CGAs in bladder cancer care and found that CGAs were successfully implemented with high rates of completion and low rates of perceived burden. Notably, in this pilot cohort of 94 patients, DCS scores did not differ significantly between patients and providers with CGA use. Future work will evaluate associations between individual instruments, treatment decisions, clinical outcomes and patient-reported quality of life measures.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2022.40.6_suppl.479
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2022
    detail.hit.zdb_id: 2005181-5
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  • 16
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    Bladder cancer rapid autopsy: A mechanism for collecting metastatic tumor tissue and establishing xenograft models of metastatic disease.
    American Society of Clinical Oncology (ASCO) ; 2018
    In:  Journal of Clinical Oncology Vol. 36, No. 6_suppl ( 2018-02-20), p. 478-478
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 36, No. 6_suppl ( 2018-02-20), p. 478-478
    Abstract: 478 Background: Patients with metastatic bladder cancer have a poor prognosis with a median survival of only 9-15 months. Understanding the biology of metastatic bladder cancer has been historically difficult due to a paucity of specimens and models that recapitulate human disease. We established a bladder cancer rapid autopsy program to systemically acquire metastases, and build patient-derived xenograft (PDX) and organoid models for biological studies. Methods: Patients with metastatic bladder cancer were consented and a rapid autopsy was performed 2-6 hours after death to allow acquisition of normal and metastasis specimens. Frozen and formalin-fixed and paraffin embedded specimens were collected and pathological evaluation was performed on each specimen. Additionally, tumors were implanted subcutaneously into SCID mice to establish PDXs. Once PDXs were developed, PDXs were dissociated for companion organoid culture. Clinical history and treatment information was documented for each patient. Results: We have performed 10 bladder cancer rapid autopsies to date, and have acquired 105 metastatic and 45 normal specimens. The pathological subtypes of patients include urothelial cell carcinoma (5/10), squamous cell carcinoma (3/10), and plasmacytoid variant of urothelial carcinoma (2/10). The cohort has been treated BCG only (1/10), chemotherapy (3/10), and chemotherapy and immune checkpoint inhibitors (6/10). The leading site of metastasis was the liver (7/10) and lung (7/10), followed by lymph node (5/10), bone (5/10), intestine (4/10), and omentum (2/10). Half (5/10) of the patients had extensive liver metastases that allow acquisition of multiple tumor foci. For the first time, PDX and organoids from two independent metastases (omentum – CoCaB 14.1 and liver –CoCaB 14.2) from the same patient were successfully developed. Conclusions: This bladder cancer rapid autopsy program provides an important volume of metastatic tumor specimens for study. Importantly, the first bladder cancer PDX derived from metastasis has been developed. The availability of metastatic bladder cancer specimens, PDXs, and organoids will allow biological studies of advanced disease.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2018.36.6_suppl.478
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2018
    detail.hit.zdb_id: 2005181-5
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  • 17
    Online Resource
    Online Resource
    Evaluating the hypothalamic-pituitary-adrenal axis (HPAA) in men receiving ketoconazole for castrate resistant prostate cancer (CRPC).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 15_suppl ( 2013-05-20), p. 5077-5077
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 15_suppl ( 2013-05-20), p. 5077-5077
    Abstract: 5077 Background: Serum adrenal androgen (AA) levels may be prognostic for survival in men with CRPC treated with androgen synthesis inhibitors (ASIs) including ketoconazole (keto) and abiraterone. We hypothesize that up-regulation of the HPAA and adrenocorticotropic hormone (ACTH) may contribute to therapeutic resistance on ASIs. The current study explores the relationship between ACTH, AA, testosterone (T) and estradiol (E) among CRPC patients (pts) treated with ASI + corticosteroids. Methods: Phase II study of keto (400 mg TID) + hydrocortisone (HC) (30 mg/day) in pts with CRPC. Pts who achieved ≥ 30% PSA decline from baseline at week 12 continued keto/HC until progression, at which point HC was replaced by dexamethasone (dex). Serum hormone (H) levels were measured (in AM) at baseline and every 4 weeks using standard assays. Statistical tests include Spearman’s rank test for correlation between baseline H levels; Wilcoxon matched pairs for baseline vs. week 4 distribution; and Fisher’s exact test for associations between H levels (dichotomized at median) with PSA decline. Results: Of 30 pts enrolled and 24 evaluable for PSA response, 13 pts (54%) achieved ≥ 30% PSA decline at 12 weeks. Baseline ACTH was positively correlated with DHEA (r = 0.40; p = 0.04) and cortisol (r = 0.52; p = 0.007). Change from baseline to week 4 in H levels is shown in table. There was a significant increase in pts achieving a PSA decline of 〉 30% if there was a decrease in E at week 4 vs. no decrease (83% vs. 18%; p = 0.003). Baseline and changes in other H levels were not associated with PSA outcome at week 12. Conclusions: ACTH is positively correlated with DHEA and cortisol in CRPC pts. Declines in E may serve as an additional predictive marker of benefit for ASI therapy. These observations require prospective validation. Analyses exploring changes in ACTH at disease progression and impact of substituting dex for HC are ongoing. Clinical trial information: NCT01036594. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.15_suppl.5077
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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  • 18
    Online Resource
    Online Resource
    Associations between baseline body composition and cancer-specific mortality following neoadjuvant chemotherapy and radical cystectomy for bladder cancer.
    American Society of Clinical Oncology (ASCO) ; 2020
    In:  Journal of Clinical Oncology Vol. 38, No. 15_suppl ( 2020-05-20), p. e17015-e17015
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 38, No. 15_suppl ( 2020-05-20), p. e17015-e17015
    Abstract: e17015 Background: Sarcopenia is a modifiable risk factor independently associated with cancer-specific mortality (CSM) in bladder cancer (BC). Sarcopenic obesity, where obesity is measured by fat mass index [FMI, total body fat (kg)/height(m) 2 ], has been proposed as an additive insult. To date, studies have overwhelmingly been performed in patients treated without neoadjuvant chemotherapy (NAC). Herein, we evaluate associations between baseline skeletal muscle index (SMI), FMI, and CSM in patients treated with NAC and radical cystectomy (RC). Methods: Lumbar SMI (cross sectional area of skeletal muscle/height 2 , cm 2 /m 2 ) was measured on a computed tomography (CT) image at the level of the third lumbar vertebral body, within 60 days prior to NAC. Total body FMI was calculated from visceral and subcutaneous fat cross-sectional areas. Patients were classified as being sarcopenic, according to sex-specific consensus definitions: Male: SMI 〈 55, Female: SMI 〈 39, and as obese if Male: FMI 〉 9, Female: 〉 13. Cancer-specific survival (CSS) was estimated using the Kaplan Meier method. Associations with CSM were summarized with multivariable Cox proportional hazards models. Results: 143 patients had CT scans of sufficient quality (2005-18). There were no significant differences in clinicopathologic characteristics between the study cohort and patients without available imaging (N = 261). Cisplatin-based NAC was given to 125 patients (87%), and 18 (13%) received other regimens. In total, 86 (60%) patients were sarcopenic, 52 (36%) obese, and 25 (17%) both sarcopenic and obese, while 48 (34%) were sarcopenic with normal FMI. Median follow-up was 2.7 years (IQR 1.2-6.2), and 43 patients died from BC. Three-year CSS was 61% (sarcopenic) vs. 77% (p 〈 0.05). Sarcopenic patients with normal FMI had the worst 3-year CSS (55%) compared to those with sarcopenia and FMI-obesity (79%), normal SMI with FMI-obesity (69%), and normal body composition (88%, p = 0.03). On multivariable analysis, neither FMI (HR: 0.77, 95% CI: 0.47-1.3, p = 0.3) nor SMI was independently associated with CSM (HR: 0.98, 95% CI: 0.96-1, p = 0.07) after adjustment for ASA score, pathologic tumor, and nodal stage. Conclusions: In patients treated with NAC+RC, pretreatment SMI trended towards independently predicting risk of CSM. Patients with sarcopenia and normal fat demonstrated the worst CSS. Further study is warranted on the impact of NAC on body composition and the role of the latter in risk stratification of this high-risk patient population.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2020.38.15_suppl.e17015
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2020
    detail.hit.zdb_id: 2005181-5
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  • 19
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    A phase II, multicenter, single-arm trial of CV301 plus atezolizumab (Atezo) in locally advanced (unresectable) or metastatic urothelial cancer (UC).
    American Society of Clinical Oncology (ASCO) ; 2019
    In:  Journal of Clinical Oncology Vol. 37, No. 7_suppl ( 2019-03-01), p. TPS494-TPS494
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 37, No. 7_suppl ( 2019-03-01), p. TPS494-TPS494
    Abstract: TPS494 Background: Anti-PD1/PD-L1 can achieve durable responses in advanced UC but most patients (pts) do not respond. Combination strategies with agents that “prime” the immune system may improve outcomes. CV301 comprises two recombinant poxviruses, Modified Vaccinia Ankara (MVA) and Fowlpox (FPV), encoding the human transgenes for CEA, MUC-1, and a Triad of Co-stimulatory Molecules (TRICOM: ICAM-1, LFA-3, and B7-1). MVA-CV301 is used for priming doses and FPV-CV301 is used for booster doses to achieve a heterologous prime boost regimen. In preclinical studies, BN-platform vaccine plus PD1/PD-L1 inhibitors exhibited synergistic anti-tumor efficacy, T-cell infiltration, and PD-L1 upregulation in tumors. CEA and MUC-1 are expressed, in 41-90% and 55-91% of any stage UC, respectively, and in ~100% of metastatic UC. An ongoing Phase Ib trial of CV301 plus anti-PD-1 agent has demonstrated a similar safety profile to anti-PD-1 monotherapy with only mild vaccine-related adverse events (AEs). Methods: This is a Phase 2, single-arm, multi-institutional trial designed to study CV301 plus atezo as 1st-line treatment in pts with advanced UC ineligible for cisplatin-based chemotherapy regardless of PD-L1 (Cohort 1) and as salvage treatment in pts with UC progressing after platinum-based chemotherapy (Cohort 2). MVA-CV301 is given subcutaneously (SC) on Days 1 and 22 and FPV-CV301 SC every 21 days for 4 doses, then every 6 weeks until 6 months, then every 12 weeks until 2 years. Atezo 1200mg is given every 21 days. Primary endpoint is objective response rate (ORR; RECIST 1.1). Secondary endpoints: immune response, OS, PFS, response duration, AEs. Tumor and serial blood samples will be collected for biomarker analyses; 1-sided α is 0.025/cohort in this design. With a 2-stage design, success criteria are based on historic ORR (H0) and alternative ORR (H1) with ≥70% power. For Cohort 1, assuming H0 = 0.23, H1 = 0.43, then Cohort 1 sample size N 1 = 14, responders required at stage 1 to continue R 1 ≥3, total accrual goal N = 33, total responders to reject H0, R≥13. For Cohort 2, assuming H0 = 0.15, H1 = 0.33, then N 1 = 13, R 1 ≥2, N = 35, R≥10. Accrual has begun; completion is expected within 1 year. Clinical trial information: NCT03628716.
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/JCO.2019.37.7_suppl.TPS494
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2019
    detail.hit.zdb_id: 2005181-5
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  • 20
    Online Resource
    Online Resource
    Evaluating the hypothalamic-pituitary-adrenal axis (HPAA) in men receiving ketoconazole for castrate-resistant prostate cancer (CRPC).
    American Society of Clinical Oncology (ASCO) ; 2013
    In:  Journal of Clinical Oncology Vol. 31, No. 6_suppl ( 2013-02-20), p. 64-64
    Details
    In: Journal of Clinical Oncology, American Society of Clinical Oncology (ASCO), Vol. 31, No. 6_suppl ( 2013-02-20), p. 64-64
    Abstract: 64 Background: Serum adrenal androgen (AA) levels may be prognostic for survival in men with CRPC treated with androgen synthesis inhibitors (ASIs) including ketoconazole (keto) and abiraterone. We hypothesize that up-regulation of the HPAA and adrenocorticotropic hormone (ACTH) may contribute to therapeutic resistance on ASIs. The current study explores the relationship between ACTH, AA, testosterone (T) and estradiol (E) among CRPC patients (pts) treated with ASI + corticosteroids. Methods: Phase 2 study of keto (400 mg TID) + hydrocortisone (HC) (30 mg/day) in pts with CRPC. Pts who achieved ≥ 30% PSA decline from baseline at week 12 continued keto/HC until progression, at which point HC was replaced by dexamethasone (dex). Serum hormone (H) levels were measured (in AM) at baseline and every 4 weeks using standard assays. Statistical tests include Spearman’s rank test for correlation between baseline H levels; Wilcoxon matched pairs for baseline vs. week 4 distribution; and Fisher’s exact test for associations between H levels (dichotomized at median) with PSA decline. Results: Of 30 pts enrolled and 24 evaluable for PSA response, 13 pts (54%) achieved ≥ 30% PSA decline at 12 weeks. Baseline ACTH was positively correlated with DHEA (r = 0.40; p = 0.04) and cortisol (r = 0.52; p = 0.007). Change from baseline to week 4 in H levels is shown in table. There was a significant increase in pts achieving a PSA decline of ≥ 30% if there was a decrease in E at week 4 vs. no decrease (83% vs. 18%; p = 0.003). Baseline and changes in other H levels were not associated with PSA outcome at week 12. Conclusions: ACTH is positively correlated with DHEA and cortisol in CRPC pts. Declines in E may serve as an additional predictive marker of benefit for ASI therapy. These observations require prospective validation. Analyses exploring changes in ACTH at disease progression and impact of substituting dex for HC are ongoing. Clinical trial information: NCT01036594. [Table: see text]
    Type of Medium: Online Resource
    ISSN: 0732-183X , 1527-7755
    URL: Article
    DOI: 10.1200/jco.2013.31.6_suppl.64
    RVK:
    XA 52760
    RVK:
    XA 10000
    Language: English
    Publisher: American Society of Clinical Oncology (ASCO)
    Publication Date: 2013
    detail.hit.zdb_id: 2005181-5
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