Phase II trial of 177lutetium radiolabeled anti-PSMA antibody J591 (177Lu-J591) for metastatic castrate-resistant prostate cancer (metCRPC): Survival update and expansion cohort with biomarkers.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 121-121
Author(s):  
Scott T. Tagawa ◽  
Naveed Hassan Akhtar ◽  
Joseph Osborne ◽  
Paul J. Christos ◽  
Shankar Vallabhajosula ◽  
...  
Keyword(s):  
Single Dose ◽  
Phase Ii ◽  
Dose Response ◽  
Phase Ii Trial ◽  
Circulating Tumor Cell ◽  
Disease Response ◽  
Cell Counts ◽  
Pre Treatment ◽  
Castrate Resistant ◽  
Expansion Cohort

121 Background: A phase II trial in men with progressive metCRPC receiving a single dose of 177Lu-J591 at 65 mCi/m2 (15 pts) or 70 mCi/m2 (phase I MTD, 17 pts) was performed without selection for PSMA expression, suggesting a larger than expected dose-response (13 vs 47% >30% PSA decline respectively), leading to an expansion cohort to validate the response rate at 70 mCi/m2. Methods: Endpoints: to validate the PSA and/or measurable disease response at 70 mCi/m2, evaluate circulating tumor cell counts (CellSearch) and pre-treatment PSMA imaging with 111In-J591 in the expansion cohort, and examine overall survival (OS) for all pts. Results: 15 additional pts were treated. Expansion cohort demographics were similar to the initial cohorts, and PSA responses and toxicity were similar to the initial cohort treated at 70 mCi/m2 (see Table), with myelotoxicity improving in all following nadir at 1 month. More PSA declines and longer OS were seen at 70 mCi/m2. 12 of 15 pts had baseline and follow up CTC counts at 4-6 weeks: 66.7% had >50% decline and 25% were unchanged at 0 or 1 (one declined 27%). Although 93.3% had accurate targeting (imaging) of known sites of disease, as seen in initial analysis, a trend for fewer > 30% PSA declines was seen with less intense PSMA imaging. Conclusions: Single dose 177Lu-J591 at70 mCi/m2 was generally well tolerated, with predictable, reversible myelosuppression, and demonstrates anti-tumor activity in pts with progressive metCRPC. A dose-response relationship was confirmed for both toxicity and activity, with improved response and OS at 70 mCi/m2. CTC declines are demonstrated. Selection of pts based upon non-invasive testing (PSMA imaging) may improve the therapeutic profile. Clinical trial information: NCT00195039. [Table: see text]

Phase II trial of bevacizumab (B) and oral satraplatin (S) and prednisone in docetaxel pretreated metastatic castrate resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e16028-e16028
Author(s):  
U. N. Vaishampayan ◽  
L. K. Heilbrun ◽  
E. I. Heath ◽  
D. W. Smith ◽  
B. Dickow ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Survival Data ◽  
Phase Ii Trial ◽  
Unmet Need ◽  
Preliminary Evidence ◽  
Time To Progression ◽  
Disease Response ◽  
Measurable Disease ◽  
Castrate Resistant

e16028 Background: In metastatic CRPC, second line therapy after docetaxel, remains a currently unmet need. Based on the efficacy and tolerability of S and B in prostate cancer, and the clinical synergy noted between chemotherapy and B, a phase II trial of the combination was conducted. Methods: Metastatic CRPC patients, with prior docetaxel based chemotherapy were eligible to receive S 80 mg/m2 orally for days 1–5, and B 10 mg/kg on day 1, and 15mg/kg on day 15 of each 35 day cycle. Prednisone was administered at a dose of 5 mg twice daily. Response was assessed every 2 cycles. Toxicity was assessed weekly during cycle 1 and on days 1 and 15 of each subsequent cycle. Primary endpoint was time to progression defined as a skeletal event, new areas of metastases on bone scans or per RECIST criteria for measurable disease. Results: 19 of 28 patients have been enrolled to date; 7 African American and 12 Caucasian,, with median age of 68.5 years and median pretherapy PSA of 137.8 ng/mL (range 16.8–994 ng/mL). 7 (44%) had bone pain, Gleason score of 7 and ≥ 8 in 7 and 12 patients respectively. Measurable disease progression was noted in 5 patients, bone scan progression in 6 patients, progression of both in 3 patients, and PSA only progression in 5 patients. 76 cycles have been administered; 7 patients continued on therapy beyond 6 cycles. The only grade 4 toxicity noted was pulmonary embolism in 2 patients, after 2 and 6 cycles of therapy. Grade 3 neutropenia, gastrointestinal toxicity, and electrolyte abnormalities were noted in 1 patient each. There were no treatment related deaths. 16/19 patients are response evaluable. 7 patients had a PSA decline of which 4 patients had a ≥30% PSA decline. 3 of 6 patients had a measurable disease response. 11 of 16 patients have progressed to date after median of 6 cycles of therapy. Time to progression and survival data will be reported. Conclusions: The combination was well tolerated, and revealed preliminary evidence of clinical efficacy in docetaxel pretreated metastatic CRPC. [Table: see text]

A phase II trial of weekly i.v. KW-2170 in advanced castrate-resistant prostate cancer

2010 ◽  
Vol 6 (4) ◽  
pp. 292-297 ◽  
Author(s):  
Paul L DE SOUZA ◽  
Scott NORTH ◽  
Graeme B BOLGER ◽  
Harris SPIRIDONIDIS ◽  
Robert LIM ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Phase II trial of cediranib (AZD2171) in docetaxel-resistant, castrate-resistant prostate cancer (CRPC)

2008 ◽  
Vol 26 (15_suppl) ◽  
pp. 5136-5136 ◽  
Author(s):  
J. J. Karakunnel ◽  
J. L. Gulley ◽  
P. M. Arlen ◽  
M. Mulquin ◽  
J. J. Wright ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant

Phase II trial of combination therapy with intravenous carboplatin (C) and oral everolimus (EVE) and prednisone (P) in docetaxel-pretreated (DP) metastatic castrate-resistant prostate cancer (mCRPC): A Prostate Cancer Clinical Trial Consortium study.

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 156-156
Author(s):  
Muthu Kumaran Veeraputhiran ◽  
Daniel H. Shevrin ◽  
Lance K. Heilbrun ◽  
Daryn Smith ◽  
Jing Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Mtor Inhibition ◽  
Measurable Disease ◽  
Grade 3 ◽  
And Performance ◽  
Castrate Resistant

156 Background: Platinum based therapies have demonstrated efficacy in DP mCRPC. EVE demonstrated preclinical efficacy in chemotherapy resistant prostate cancer models. Clinical synergy was noted between C and EVE, hence a phase II trial of the combination was conducted. Methods: Primary endpoint was time to progression (TTP). Progression was defined per RECIST criteria for measurable disease (MD), or skeletal event, or > 2 new areas of bone metastases. DP mCRPC patients with adequate renal and liver function, and performance status of 0 or 1 were eligible. Intravenous C at target AUC of 5 on day 1, and oral EVE 5mg once daily and P 5mg twice daily were administered in 21 day cycles. PSA was assessed every 21 days and radiologic response was assessed every 3 cycles. Secondary endpoints included overall survival (OS), correlation of TTP and PSA response, with markers such as phopho mTOR, pAKT, p70S6 and circulating tumor cells (CTC). Results: 26 patients (pts) enrolled, including 8 African Americans, and accrual is complete. Median age was 69 years (range 54-86). Median pretherapy PSA was 190 ng/ml (range 13 - 2174). 18 pts (69%) had bone pain. Gleason score was > 8 in 18 pts. 19 pts had measurable disease of which 15 had MD progression, 18 had bone scan progression, and 2 had PSA-only progression. 124 cycles have been administered; median 3 cycles (range 1 - 16). The predominant grade 3 or 4 toxicities were thrombocytopenia in 8 pts, pulmonary embolism in 2 and neutropenia in 3. No treatment related deaths occurred. Of 26 pts who are response evaluable, 4 (15%) had a > 30% PSA decline and 1 had a >90% PSA decline. Of 19 pts with MD, 8 had stable disease and no objective responses were observed. The median TTP and OS were 2.5 months (90% CI: 1.8 - 4.3), and 12.5 months (90% CI: 6.7 - 16.1), respectively. Correlative studies including pharmacokinetic and pharmacodynamic evaluations are ongoing, and will be reported. Conclusions: The combination was tolerable but revealed modest clinical efficacy. Biomarker evaluation may help identify a subset likely to benefit from mTOR inhibition strategy in mCRPC. Clinical trial information: NCT01051570.

Phase II trial of circulating cytokines as markers of docetaxel (DTX) resistance in metastatic castrate-resistant prostate cancer (mCRPC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. 5039-5039
Author(s):  
Kate Lynette Mahon ◽  
Hui-Ming Lin ◽  
Calan Spielman ◽  
Michelle Lee-Ng ◽  
Howard Gurney ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase Ii ◽  
Phase Ii Trial ◽  
Castrate Resistant Prostate Cancer ◽  
Castrate Resistant ◽  
Circulating Cytokines

Everolimus (E) plus bevacizumab (B) is effective first-line treatment for patients (pts) with advanced renal cell carcinoma (RCC) with papillary features (PF): Results from a phase II trial.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 627-627 ◽  
Author(s):  
Darren R. Feldman ◽  
Chung-Han Lee ◽  
Ana M. Molina ◽  
Andrea Knezevic ◽  
Yingbei Chen ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Objective Response ◽  
Significant Activity ◽  
Line Treatment ◽  
First Line ◽  
Total N ◽  
Papillary Rcc ◽  
Expansion Cohort ◽  
First Line Treatment

627 Background: We previously reported on a phase II trial of E+B across various non-clear cell RCC histologies and observed significant activity among pts with papillary or unclassified RCC ( uRCC ) with PF (objective response rate [ORR] 39%, median progression-free survival [PFS] 12.9 months [m]; Voss, JCO, 2016). An expansion cohort limited to these two histologies was conducted to confirm the efficacy of E+B. Methods: E + B was administered at standard doses until progressive disease (PD) or intolerance to therapy. The current analysis included 19 pts with pRCC or uRCC with PF in the initial cohort and 20 pts in the expansion cohort (total n=39). The primary endpoint was 6 month PFS with secondary endpoints of ORR, median PFS, and overall survival (OS). Correlative analyses included next generation sequencing (NGS) from tumor and germline across >341 genes of interest. Results: Of 39 pts, 24 had uRCC with PF, 14 had papillary RCC, and 1 had translocation RCC with PF. Among 37 evaluable pts, the ORR was 35%; 43% for uRCC with PF and 23% for papillary RCC. Six-month PFS for all 39 pts was 78%; 82% for uRCC with PF and 68% for papillary RCC. Median PFS was 13.7m; 13.7m for uRCC with PF and 8.4m for papillary RCC (Table). With median followup of 17.6m, median OS is 33.9m. Toxicity with E+B was similar to previous reports. 33 of 39 pts had NGS performed and partial responses were observed across a wide spectrum of genomic alterations, including several recurrently seen in papillary RCC variants such as mutations in FH, MET, NF2, and ARID1a. Conclusions: The expansion cohort confirms the activity of E+B for pts with advanced papillary RCC or uRCC with PF with superior ORR, PFS, and OS compared to historical results with sunitinib for these histologies. E+B represents a new standard first-line treatment option for these pts. Clinical trial information: NCT01399918. [Table: see text]

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