scholarly journals A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE).

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 116-116
Author(s):  
Phuoc T. Tran ◽  
Ryan Phillips ◽  
William Shi ◽  
Su Jin Lim ◽  
Emmanuel S. Antonarakis ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Randomized Trial ◽  
Phase Ii ◽  
Cell Receptor ◽  
Circulating Tumor Dna ◽  
Oncologic Outcomes ◽  
Radiation Fields ◽  
Oligometastatic Prostate Cancer ◽  
Hormone Sensitive ◽  
Grade 3

116 Background: Mounting evidence supports metastatic ablation for oligometastatic prostate cancer (OMPC). Importantly, biomarkers to determine patients who benefit most from complete ablation are unknown. We hypothesize that stereotactic ablative radiation (SABR) will improve oncologic outcomes in men with OMPC. Methods: In this phase II randomized trial, men with recurrent hormone-sensitive OMPC (1-3 radiation fields) were stratified by primary management (radiotherapy vs surgery), PSA doubling time, and prior androgen deprivation therapy and randomized 2:1 to SABR or observation (OBS). The primary endpoint was progression at 6 months by PSA (≥ 25% increase and ≥ nadir + 2 ng/mL), conventional imaging (RECIST 1.1 criteria or new lesion on bone scan), or symptomatic decline. Tissue, liquid and imaging correlatives were analyzed as biomarkers. Results: From 5/2016-3/2018, 54 patients were randomized. Progression at six months occurred in 19% of SABR patients and 61% of observation patients [p=0.005]. SABR improved median PFS (not reached vs 5.8 months, HR 0.30, p = 0.0023). Total consolidation of PSMA radiotracer-avid disease decreased the risk of new lesions at six months (16% vs 63%, p = 0.006). No toxicity ≥ grade 3 was observed. T-cell receptor sequencing identified increased clonotypic expansion (p = 0.03) following SABR and correlation between baseline clonality and progression with SABR only. Analysis of circulating tumor DNA (ctDNA) and germline mutations identified a mutation profile that was associated with benefit from SABR. Conclusions: SABR for OMPC improves outcomes and is enhanced by total consolidation of disease identified by PSMA-targeted PET. SABR induces a systemic immune response, and baseline immune phenotype and tumor mutation status may predict the benefit from SABR. These results underline the importance of prospective randomized investigation of the oligometastatic state with integrated imaging and biological correlates. Clinical trial information: NCT02680587.

scholarly journals A phase II randomized trial of Observation versus stereotactic ablative RadiatIon for OLigometastatic prostate CancEr (ORIOLE)

BMC Cancer ◽  
2017 ◽  
Vol 17 (1) ◽  
Author(s):  
Noura Radwan ◽  
Ryan Phillips ◽  
Ashley Ross ◽  
Steven P. Rowe ◽  
Michael A. Gorin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Randomized Trial ◽  
Phase Ii ◽  
Oligometastatic Prostate Cancer

Phase II study of intravenous vinorelbine plus hormone therapy in hormone-refractory prostate cancer

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 14601-14601
Author(s):  
E. Silva ◽  
F. Silva
Keyword(s):  
Prostate Cancer ◽  
Elderly Patients ◽  
Prostate Specific Antigen ◽  
Phase Ii ◽  
Performance Status ◽  
Specific Antigen ◽  
Hormone Refractory Prostate Cancer ◽  
Phase Ii Studies ◽  
Hormone Refractory ◽  
Grade 3

14601 Background: Vinorelbine (VRL) has been shown to be active in hormone-refractory prostate cancer (HRPC) in Phase II studies, alone or in combination. Its moderate toxicity profile is well tolerated in elderly patients. The purpose of this study was the investigation of the efficacy of vinorelbine and its toxicity. Methods: Patients with metastatic prostate cancer, progressive after hormonal therapy, receive intravenous VRL 30 mg/m2 on days 1 and 8 every 3 weeks, and hydrocortisone 40 mg/day. Previous chemotherapy was allowed if stopped 6 months before. 44 received VRL according to the protocol. Inclusion criteria: hormone refractory prostate cancer patients PSA >20; performance status WHO < 2. The primary endpoint was prostate specific antigen (PSA) levels, pain, and WHO performance status. Their mean (range) age was 71 (45–80) years, their median prostate specific antigen (PSA) level was 286 (38–950) ng/ml, and the median Gleason score was 8 (7 to 9). 38 patients had had previous chemotherapy. Results: Among the 44 patients, 7 with less than 3 cycles were not evaluated. Patients received a mean (range) of 9 (3–44) cycles of therapy. 6 patients (14%) had not been dispensed prior chemotherapy and 38 (86%) had; 19 (43%) had 2 lines of chemotherapy and 19 (43%) had 1 line. The median follow-up was 13 months. There were no reported drug related Grade 3 toxicities. Only 2 patients required a blood transfusion. Tumour responses: 7 (16%); 17 (39%) PSA stable; 13 (29%) PSA progression, 7 not evaluated. Time of PSA response was 7 months; time to progression: 7 months. Conclusions: Vinorelbine (VRL) is a safe regimen in previous poly-chemotherapy treated hormone-refractory prostate cancer elderly patients and even with response and efficacy. No significant financial relationships to disclose.

Ixabepilone, mitoxantrone, and prednisone in patients with metastatic castration-resistant prostate cancer refractory to docetaxel-based therapy: A phase II study of the DOD Prostate Cancer Clinical Trials Consortium

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5058-5058
Author(s):  
E. Small ◽  
A. Harzstark ◽  
V. K. Weinberg ◽  
D. C. Smith ◽  
P. Mathew ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trials ◽  
Phase Ii ◽  
Vasovagal Syncope ◽  
Objective Response ◽  
Study Drug ◽  
Cancer Clinical Trials ◽  
Second Line ◽  
Castration Resistant Prostate Cancer ◽  
Grade 3

5058 Background: Mitoxantrone (M) plus prednisone (P) and ixabepilone (Ix) each have modest, non cross-resistant activity as second line chemotherapy regimens in docetaxel-refractory patients with CRPC. These agents were therefore combined in a phase I study which demonstrated anti-cancer activity and defined the recommended phase II dose used in this trial. Methods: Patients with metastatic CRPC and progression after 3 or more cycles of docetaxel were enrolled in a phase II multicenter study of the combination of prednisone 5 mg BID, Ix (35 mg/m2) and M (12 mg/m2) administered intravenously on day 1 every 21 days, with pegfilgrastim (6 mg on day 2) support. Results: To date, 43 pts have been enrolled and have received a median of 4 cycles. Of 37 patients currently evaluable for response, 14 (38%; 95% CI: 22–55%) have had a confirmed ≥50% decline in PSA and 19 (51%; 95% CI 34–68%) have had a confirmed ≥30% decline in PSA. Two of 15 patients with evaluable measurable disease (13%) have had a RECIST-defined objective response. All 43 patients are evaluable for toxicity. Grade 3 or 4 neutropenia was seen in 6 pts (17%) and grade 3 or 4 thrombocytopenia was seen in 3 (8%). Nonhematologic grade 3/4 events possibly related to study drug have included grade 3 fatigue (3 pts), grade 3 pneumonia (2 pts), and grade 3 atrial fibrillation, grade 4 myocardial infarction, grade 4 prostatitis, grade 3 nausea/vomiting, grade 3 neuropathy, grade 3 elevated transaminases, grade 3 dizziness, grade 3 dehydration, grade 3 shortness of breath, and grade 4 vasovagal syncope (1 pt each). Grade 2 neuropathy has been seen in 4 patients. Conclusions: The Ix, M, P regimen is active as second-line therapy in CRPC patients with progressive disease after docetaxel therapy and is reasonably well tolerated. Further investigation of this regimen is warranted. This study was supported in part by CTEP/NCI and the DOD Prostate Cancer Clinical Trials Consortium. [Table: see text]

Use of serum and tissue biomarker analysis embedded in a phase II clinical trial of cytarabine in castration-refractory prostate cancer to investigate prostate cancer biology.

2011 ◽  
Vol 29 (7_suppl) ◽  
pp. 59-59
Author(s):  
S. Niraula ◽  
U. Emmeneger ◽  
L. Adams ◽  
I. Tannock ◽  
S. S. Sridhar ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Cancer Biology ◽  
Target Therapy ◽  
Phase Ii Clinical Trial ◽  
Mrna Levels ◽  
Cancer Genes ◽  
Biomarker Analysis ◽  
Grade 3

59 Background: Other than the androgen receptor, the TMPRSS2-ERG genomic aberrations in prostate cancer provide the first recent opportunity to target therapy in castration refractory prostate cancer (CRPC). We initiated a phase II clinical trial of cytarabine in docetaxel refractory CRPC on the basis of microarray, in vitro and case report evidence that cytarabine may be particularly effective in men harbouring abnormalities of the ERG oncogenes. Embedded in this clinical trial was the first use of blood mRNA levels of prostate cancer related genes as biomarkers of response and prognosis. Methods: Patients with docetaxel refractory progressive CRPC received intravenous cytarabine at doses between 1g/m2-0.25 g/m2 q3 weekly. Responses were defined according to PCWG2C. 10 patients were enrolled between June 2007 and January 2010. TMPRSS2:ERG, PSA and PCA3 mRNA copies in whole blood collected with PAXgene tubes at the beginning of each cycle and at trial termination were quantified using transcription-mediated amplification assays. The prototype TMPRSS2:ERG assay detects the gene fusion isoform TMPRSS2 exon1 to ERG exon4. Results: No patients demonstrated a serum PSA response (PCWG2C). The average number of cycles administered was 2.6. Significant toxicities including grade 3-4 thrombocytopenia (2) and grade 3-4 neutropenia (3). These toxicities necessitated several dose reductions in the protocol, however most patients were removed from trial for serum PSA progression alone. PCA3 and PSA mRNAs were detectable in 8/10 and 9/10 cases, respectively; there was no correlation between serum PSA and PCA3 or PSA mRNA copy levels in blood. Testing for TMPRSS2:ERG in blood was able to predict the presence or absence of the TMPRSS2-ERG rearrangement in 9/10 cases when compared to 3 colour FISH carried out on baseline biopsies/ prostatectomies (2/10 positive for Exon 4:Exon 1 deletion). Conclusions: Cytarabine administation is ineffective in docetaxel refractory CRPC. Blood mRNA levels of prostate cancer genes reveal novel aspects of prostate cancer biology and have implications for the understanding of circulating tumour cells. [Table: see text]

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