A randomized phase I/II study to examine the contribution of carboplatin to cabazitaxel for the treatment of men with metastatic castration-resistant prostate cancer (mCRPC) with and without anaplastic features.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 148-148
Author(s):  
Paul Gettys Corn ◽  
Shi-Ming Tu ◽  
Amado J. Zurita ◽  
John C. Araujo ◽  
Lance C. Pagliaro ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Randomized Study ◽  
Specific Antigen ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Platinum Based Chemotherapy ◽  
Grade 3 ◽  
Carboplatin Auc

148 Background: We recently described “anaplastic” prostate carcinomas (PC), a clinically distinct variant of lethal castration-resistant prostate cancer (CRPC) that share clinical features with small cell carcinomas despite heterogeneous morphology. To test the hypothesis that anaplastic PC are uniquely sensitive to platinum-based chemotherapy, we designed a randomized study of cabazitaxel with or without carboplatin in men with metastatic CRPC (mCRPC) stratified for the presence of at least 1 of 7 previously published anaplastic criteria (Aparicio, Clin Cancer Res 2013;19). Here we report results of the phase I study. Methods: Patients (pts) received intravenous cabazitaxel with carboplatin every 21 days with growth factor support and were imaged every two cycles. A 3+3 sequential dose-escalation design was employed to assess the frequency of dose-limiting toxicity after cycle one and establish a maximal tolerated dose (MTD). Three cohorts were tested: (i) cabazitaxel 20mg/m2 – carboplatin AUC 3, (ii) cabazitaxel 25 mg/m2 – carboplatin AUC 3, and (iii) cabazitaxel 25 mg/m2 - carboplatin AUC 4. Up to 10 cycles were administered in the absence of progression or toxicity. Results: Nine men with mCRPC (five anaplastic) previously treated with docetaxel, received a median of six cycles (2 to 10). All had bone involvement and 6 of 9 had RECIST measurable disease. An MTD was not identified. All pts reported 1 or more adverse event (AE) possibly treatment related (120 Grade 1; 53 Grade 2; 13 Grade 3), most commonly fatigue, anemia, nausea, and diarrhea. Grade 3 AE included anemia (n=2), fatigue (n=1), thrombocytopenia (n=1), hypomagnesemia (n=1), diarrhea (n=1), hypokalemia (n=1), and anorexia (n=1). Prostate-specific antigen declines of more than 70% occurred in 6 of 9 (67%) pts. Two of 6 pts had a partial response, three had stable disease, and one progressed. For pts with elevated bone markers at baseline, 2 of 3 had more than 50% declines in BAP and 4 of 7 had more than 30% declines in urinary N-telopeptide levels. Conclusions: The combination of cabazitaxel and carboplatin is safe and has significant clinical activity. The randomized phase II portion combines cabazitaxel 25 mg/m2 and carboplatin AUC4. Results will be updated at the time of the meeting. Clinical trial information: NCT01505868.

scholarly journals Phase I Study of Ixabepilone, Mitoxantrone, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer Previously Treated With Docetaxel-Based Therapy: A Study of the Department of Defense Prostate Cancer Clinical Trials Consortium

2009 ◽  
Vol 27 (17) ◽  
pp. 2772-2778 ◽  
Author(s):  
Jonathan E. Rosenberg ◽  
Charles J. Ryan ◽  
Vivian K. Weinberg ◽  
David C. Smith ◽  
Maha Hussain ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Phase I ◽  
Specific Antigen ◽  
Maximum Tolerated Dose ◽  
Castration Resistant Prostate Cancer ◽  
Disease Response ◽  
Castration Resistant ◽  
Grade 5 ◽  
Grade 3 ◽  
Recommended Phase Ii Dose

Purpose Mitoxantrone plus prednisone and ixabepilone each have modest activity as second-line chemotherapy in docetaxel-refractory castration-resistant prostate cancer (CRPC) patients. Clinical noncrossresistance was previously observed. Patients and Methods Metastatic CRPC patients progressing during or after taxane-based chemotherapy enrolled in a phase I multicenter study of ixabepilone and mitoxantrone administered every 21 days along with prednisone. Ixabepilone and mitoxantrone doses were alternately escalated in a standard 3 + 3 design. Patients were evaluated for toxicity and disease response. Dose-limiting toxicities (DLTs) were defined as treatment related, occurring during cycle 1, and included grade 4 prolonged or febrile neutropenia, thrombocytopenia (grade 4 or grade 3 with bleeding), or ≥ grade 3 nonhematologic toxicity. Results Thirty-six patients were treated; 59% of patients experienced grade 3/4 neutropenia. DLTs included grade 3 diarrhea (n = 1), prolonged grade 4 neutropenia (n = 4), and grade 5 neutropenic infection (n = 1). Due to prolonged neutropenia, the highest dose levels were repeated with pegfilgrastim on day 2 of each cycle. The maximum tolerated dose in combination with pegfilgrastim was not exceeded. The recommended phase II dose is mitoxantrone 12 mg/m2 and ixabepilone 35 mg/m2 every 21 days, pegfilgrastim 6 mg subcutaneously day 2, and continuous prednisone 5 mg twice per day. Thirty-one percent of patients have experienced ≥ 50% prostate-specific antigen (PSA) declines, and two experienced objective responses. Of 21 patients treated with mitoxantrone 12 mg/m2 plus ixabepilone ≥ 30 mg/m2, nine (43%) experienced ≥ 50% PSA declines (95% CI, 22% to 66%). Conclusion These results suggest that the combination of ixabepilone and mitoxantrone is feasible and active in CRPC and requires dosing with pegfilgrastim.

scholarly journals Phase I Clinical Trial of the CYP17 Inhibitor Abiraterone Acetate Demonstrating Clinical Activity in Patients With Castration-Resistant Prostate Cancer Who Received Prior Ketoconazole Therapy

2010 ◽  
Vol 28 (9) ◽  
pp. 1481-1488 ◽  
Author(s):  
Charles J. Ryan ◽  
Matthew R. Smith ◽  
Lawrence Fong ◽  
Jonathan E. Rosenberg ◽  
Philip Kantoff ◽  
...  
Keyword(s):  
Phase I ◽  
Locally Advanced ◽  
Specific Antigen ◽  
Distant Metastases ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Dose Escalation Study ◽  
Castration Resistant ◽  
Grade 3

Purpose Abiraterone acetate is a prodrug of abiraterone, a selective inhibitor of CYP17, the enzyme catalyst for two essential steps in androgen biosynthesis. In castration-resistant prostate cancers (CRPCs), extragonadal androgen sources may sustain tumor growth despite a castrate environment. This phase I dose-escalation study of abiraterone acetate evaluated safety, pharmacokinetics, and effects on steroidogenesis and prostate-specific antigen (PSA) levels in men with CPRC with or without prior ketoconazole therapy. Patients and Methods Thirty-three men with chemotherapy-naïve progressive CRPC were enrolled. Nineteen patients (58%) had previously received ketoconazole for CRPC. Bone metastases were present in 70% of patients, and visceral involvement was present in 18%. Three patients (9%) had locally advanced disease without distant metastases. Fasted or fed cohorts received abiraterone acetate doses of 250, 500, 750, or 1,000 mg daily. Single-dose pharmacokinetic analyses were performed before continuous daily dosing. Results Adverse events were predominantly grade 1 or 2. No dose-limiting toxicities were observed. Hypertension (grade 3, 12%) and hypokalemia (grade 3, 6%; grade 4, 3%) were the most frequent serious toxicities and responded to medical management. Confirmed ≥ 50% PSA declines at week 12 were seen in 18 (55%) of 33 patients, including nine (47%) of 19 patients with prior ketoconazole therapy and nine (64%) of 14 patients without prior ketoconazole therapy. Substantial declines in circulating androgens and increases in mineralocorticoids were seen with all doses. Conclusion Abiraterone acetate was well tolerated and demonstrated activity in CRPC, including in patients previously treated with ketoconazole. Continued clinical study is warranted.

scholarly journals Cabazitaxel for Metastatic Castration-Resistant Prostate Cancer: Retrospective Data Analysis from an Indian Centre

2016 ◽  
Vol 9 (2) ◽  
pp. 506-515
Author(s):  
Vanita Noronha ◽  
Amit Joshi ◽  
Vamshi Krishna Muddu ◽  
Vijay Maruti Patil ◽  
Kumar Prabhash
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Free Survival ◽  
Castration Resistant ◽  
Retrospective Data Analysis ◽  
Grade 3 ◽  
Named Patient Programme

Objective: To determine the efficacy and safety of cabazitaxel in metastatic castration-resistant prostate cancer (mCRPC) patients from the named patient programme (NPP) at our centre. Methods: mCRPC patients who progressed on docetaxel were given cabazitaxel intravenously every 3 weeks until disease progression or unacceptable toxicity occurred. Overall survival, progression-free survival, prostate-specific antigen response, quality of life (QOL) changes, and safety were reported. Results: Nine men received cabazitaxel (median: 7 cycles; range: 1–27) under the NPP and were followed until death. Median survival was 14.07 months (1.07–23.80) and progression-free survival was 2.67 months (1.07–20.27). QOL was stable for most patients. Common adverse events (grade ≥3) were neutropenia (n = 8), anaemia (n = 4), and leucopenia (n = 4). Conclusion: These data from 9 patients are consistent with the results reported in the TROPIC study with a manageable safety profile.

Low-Dose Docetaxel Combined with Dexamethasone Is Feasible for Patients with Castration-Resistant Prostate Cancer

Chemotherapy ◽  
2015 ◽  
Vol 61 (1) ◽  
pp. 23-31 ◽  
Author(s):  
Noriyoshi Miura ◽  
Nozomu Tanji ◽  
Yutaka Yanagihara ◽  
Terutaka Noda ◽  
Seiji Asai ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Low Dose ◽  
Specific Antigen ◽  
Progression Free Survival ◽  
Hematological Toxicity ◽  
Castration Resistant Prostate Cancer ◽  
Gastric Bleeding ◽  
Castration Resistant ◽  
Analgesic Agents ◽  
Grade 3

Aim: Docetaxel-based chemotherapy against castration-resistant prostate cancer (CRPC) has recently been shown to be effective and tolerable. The objective of this study was to retrospectively evaluate the efficacy and toxicity of low-dose docetaxel in combination with dexamethasone. Methods: Thirty-seven CRPC patients were administered a treatment regimen consisting of 50 mg/m2 docetaxel once every 3-4 weeks and 1 mg dexamethasone daily at our institution, between November 2004 and April 2014. Results: Twenty-four patients (65%) had a decrease in serum prostate-specific antigen (PSA) >50%. The median overall survival (OS) and PSA progression-free survival were 26.2 and 10.0 months, respectively. Ten of 12 patients (83%) taking analgesic agents reduced their intake because of decreased pain levels. Grade 3 febrile neutropenia occurred in 2 patients (5%). Nonhematological toxicities were less frequent but sometimes severe. Treatment-related death occurred in 2 octogenarian patients, 1 due to gastric bleeding and the other due to infective endocarditis. Conclusion: Low-dose docetaxel in combination with dexamethasone is feasible in Japanese CRPC patients. Hematological toxicity is less than that seen with standard docetaxel therapy, but it is necessary to monitor patients for severe nonhematological toxicities, particularly very elderly patients.

KEYNOTE-046 (Part B): Effects of ADXS-PSA in combination with pembrolizumab on survival in metastatic, castration-resistant prostate cancer patients with or without prior exposure to docetaxel.

2020 ◽  
Vol 38 (6_suppl) ◽  
pp. 126-126 ◽  
Author(s):  
Mark N. Stein ◽  
Lawrence Fong ◽  
Anthony E. Mega ◽  
Elaine Tat Lam ◽  
John W. Heyburn ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Phase 1 ◽  
Specific Antigen ◽  
Prior Exposure ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Clinical Trial Information

126 Background: ADXS-PSA, an attenuated Listeria monocytogenes-based immunotherapy targeting prostate-specific antigen (PSA), is currently being evaluated in combination with pembrolizumab as a treatment for progressive metastatic castration-resistant prostate cancer (mCRPC) in the phase 1/2 KEYNOTE-046 trial (Part B). Methods: A total of 37 patients received 1x109 CFU + 200 mg pembro IV every 3 wks, for up to 2 yrs or until progression/toxicity. Results: At entry, patients were ~70 yrs with median a Gleason score of 9, and bone predominant disease (70%). MSI-High was negative in 36 pts who were able to be tested. Eighteen (48.6%) patients had received prior docetaxel, 15 pts of whom (83.3%) had also received 1-2 next generation hormonal agents (NGHAs). Nineteen (51.3%) had not received prior docetaxel and 16 of these pts (84.2%) had received 1-2 NGHAs. Overall, 16 out of 37 pts (43%) had a decreased PSA post-BL with 6/37 (16%) pts achieving a confirmed PSA reduction ≥50% from baseline. The median OS (months) for the whole group (37 pts) was 33.6 m (95% CI, range 15.4-33.6 months). The mOS for pts with and without prior exposure to docetaxel was 16 m (5.9 -33.6) and NR at 30 months of follow-up (15.4-NR), respectively. Prolonged survival was observed in pts regardless of prior therapies, microsatellite stable (MSS) status or PSA delta <50% or ≥50%. Conclusions: Results with ADXS-PSA in combination with pembrolizumab in mCRPC, with or without prior docetaxel, show promising clinical activity to be further assessed in randomized studies. Clinical trial information: NCT02325557.

scholarly journals Phase II Trial of Bevacizumab, Thalidomide, Docetaxel, and Prednisone in Patients With Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (12) ◽  
pp. 2070-2076 ◽  
Author(s):  
Yang-Min Ning ◽  
James L. Gulley ◽  
Philip M. Arlen ◽  
Sukyung Woo ◽  
Seth M. Steinberg ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Combination Therapy ◽  
Phase Ii ◽  
Specific Antigen ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Time To Progression ◽  
Castration Resistant ◽  
Phase Ii Studies

Purpose We previously demonstrated that thalidomide appears to add to the activity of docetaxel in metastatic castration-resistant prostate cancer (CRPC). Phase II studies combining docetaxel with bevacizumab have had substantial antitumor activity. We hypothesized that the combination of docetaxel plus these antiangiogenic drugs with different targets would have substantial clinical activity. To explore safety and efficacy, this was tested in mice and in human patients. Patients and Methods Preclinical efficacy of the combination therapy was evaluated in PC3 xenograft mice. Sixty patients with progressive metastatic CRPC received intravenous docetaxel and bevacizumab plus oral thalidomide and prednisone. The primary end point was a prostate-specific antigen (PSA) decline of ≥ 50%. Secondary end points included time to progression, overall survival, and safety. Results In the mouse model, combination therapy of docetaxel, bevacizumab, and thalidomide inhibited tumor growth most effectively. In the clinical trial, 90% of patients receiving the combination therapy had PSA declines of ≥ 50%, and 88% achieved a PSA decline of ≥ 30% within the first 3 months of treatment. The median time to progression was 18.3 months, and the median overall survival was 28.2 months in this group with a Halabi-predicted survival of 14 months. While toxicities were manageable, all patients developed grade 3/4 neutropenia. Conclusion The addition of bevacizumab and thalidomide to docetaxel is a highly active combination with manageable toxicities. The estimated median survival is encouraging, given the generally poor prognosis of this patient population. These results suggest that definitive clinical trials combining antiangiogenic agent combinations with docetaxel are warranted to improve treatment outcomes for patients with metastatic CRPC.

Results of a phase II trial of abiraterone acetate (AA) combined with dutasteride (DUT) for men with metastatic castration resistant prostate cancer (mCRPC).

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 126-126
Author(s):  
Rana R. McKay ◽  
Lillian Werner ◽  
Katherine A. Zukotynski ◽  
Liran Domachevsky ◽  
Aymen Elfiky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Bone Scan ◽  
Specific Antigen ◽  
Abiraterone Acetate ◽  
Type I ◽  
Castration Resistant Prostate Cancer ◽  
Prior Therapy ◽  
Castration Resistant ◽  
Psa Nadir ◽  
Grade 3

126 Background: Although abiraterone acetate (AA), a CYP17 inhibitor, increases survival in men with metastatic castration resistant prostate cancer (mCRPC), tumors eventually progress on therapy. The primary purpose of this study was to identify mechanisms of resistance to AA via analysis of the androgen receptor signaling pathway in serial tumor biopsies of men receiving AA and dutasteride (DUT), a type I and II 5-α reductase inhibitor. In this analysis, we report secondary endpoints including prostate specific antigen (PSA) response, toxicity, and incidence of flare. Methods: We enrolled 40 men with mCRPC. Patients initially received AA (1,000 mg daily) and prednisone (5 mg daily). After two months (mos), DUT (3.5 mg daily) was added. Therapy was continued until radiographic progression. A flare was recorded on bone scan, CT, or both if there were worsening lesions from baseline to 3 mos, decreasing PSA more than 50% from baseline at 3 mos, and stabilization or reduction of lesions at 6 mos. Results: Median follow-up was 13 mos. At the time of analysis, nine men remain on treatment. Twenty five percent and 18% of men received prior therapy with ketoconazole and/or chemotherapy, respectively. The median PSA at baseline was 28.8 ng/mL. After 2 mos of AA, median PSA declined by 54% to 10.9 ng/mL. Median PSA nadir was 6.3 ng/mL, reached at a median of 3.2 mos from baseline. 34 men (85%) experienced some degree of PSA decline. Twenty four men (60%) had a greater than or equal to 50% PSA decline and 12 (30%) had a greater than or equal to 90% PSA decline, reached at a median of 1.4 and 2.4 mos from baseline, respectively. There were 73% grade 1, 23% grade 2, 4% grade 3, and no grade 4 adverse events (AEs).AEs of interest included fatigue (45%), hypertension (38%, n=2 grade 3), hypokalemia (15%, n=0 grade 3), liver function test increases (15%), and edema (2%, n=0 grade 3). Seventeen men had imaging available for analysis, of whom four (23%) had flare on both 3 mos CT and bone scan and four (23%) had flare on only 3 mos CT scan. Conclusions: Given time of median PSA nadir, DUT may enhance efficacy of AA, though this warrants further investigation. Therapy with AA, prednisone (5 mg daily), and DUT is well tolerated with low rates of severe mineralocorticoid toxicity. Flare is seen on imaging in 47% of patients receiving AA. Biopsy data evaluating mechanisms for resistance to AA are not yet available. Clinical trial information: NCT01393730.

Clinical activity of abiraterone acetate in patients with castration-resistant prostate cancer who received prior ketoconazole therapy.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 99-99 ◽  
Author(s):  
Bo Zhao ◽  
Jorge A. Garcia ◽  
Timothy D. Gilligan ◽  
Brian I. Rini ◽  
Robert Dreicer
Keyword(s):  
Prostate Cancer ◽  
Specific Antigen ◽  
Underlying Mechanism ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Drug Discontinuation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Psa Response ◽  
Psa Progression

99 Background: Studies have shown activity of Abiraterone acetate (AA) in patients (pts) with castration-resistant prostate cancer (CRPC) who have received prior ketoconazole. Prostate-specific antigen (PSA) response to AA in relation to previous PSA response to ketoconazole was investigated. Methods: A retrospective analysis was conducted to determine the clinical activity of AA in men with CRPC who have received prior ketoconazole therapy at our institution. Time to PSA progression (PSA TTP) was defined by PCWG2 criteria, a PSA reduction of 50% or more was considered as PSA response. Results: Thirty four pts were identified. Nineteen pts (56%) had previous PSA responses on ketoconazole, with a median PSA TTP of 11 months (95% confidence interval [CI] 6.8-19.9). Subsequently, 11 of 34 (33%) of pts achieved a PSA response on AA, with a median PSA TTP of 6 months (95% CI 4.9-9.5). Among the 19 pts having a PSA response on ketoconazole, only four (21%) pts subsequently had PSA response to AA. Two of these pts had transient PSA response with PSA TTP less than 3 months on kKetoconazole, one patient discontinued Ketoconazole due to side effects, one patient had intermittent non-castrate testosterone levels. In contrast, 7 of 15 (46.7%) pts without prior PSA response to ketoconazole subsequently achieved PSA response on AA (p=0.11). Of note, PSA reduction of less than 50% on AA was observed in 9 of 34 pts (26%), which was associated with a longer median PSA TTP compared to pts who had PSA-progressive disease (5.9 months [95% CI 3.5-7.3] vs.1.5 months [95% CI 1.0-3.5], p=0.028). Five of these nine patients had a prior PSA response to ketoconazole but required drug discontinuation for reasons other than disease progression. Conclusions: PSA response to prior ketoconazole therapy is associated with lower PSA response rate to subsequent AA. The observation suggests that there is a biologically distinct subset of patients who are ketoconazole-resistant but abiraterone-sensitive, the underlying mechanism needs to be further investigated.

A phase I study of CNTO328, an anti-interleukin (IL)-6 monoclonal antibody combined with docetaxel in subjects with metastatic castration-resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5063-5063
Author(s):  
G. Hudes ◽  
S. Tagawa ◽  
Y. Whang ◽  
M. Qi ◽  
X. Qin ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Dose Escalation ◽  
Specific Antigen ◽  
Patient Characteristics ◽  
Major Effect ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Reactive Protein ◽  
Grade 3 ◽  
Induced Apoptosis

5063 Background: IL-6 is a potential mediator of prostate cancer morbidity and mortality and may protect prostate cancer cells from chemotherapy-induced apoptosis. CNTO328, a chimeric anti-IL-6 antibody, has been shown to inhibit prostate tumor growth in xenograft mouse models. Methods: Chemotherapy-naïve patients with metastatic CRPC were administered CNTO328 in combination with T (75 mg/m2 q3w) in 3 dose-escalation cohorts (6 mg/kg q2w, and 9 and 12 mg/kg q3w) following an initial run-in cycle of T alone to examine the effect of CNTO328 on T pharmacokinetics (PK). Safety was evaluated prior to each dose escalation. Prostate specific antigen (PSA), radiological response, and C-reactive protein (CRP), the best-known surrogate of serum IL-6 bioactivity, were also assessed. Results: This study is fully enrolled December 2008 with 38 patients. 36 patients with KPS ≥70, median age 66 (range 43–82) received 6 (median) cycles of T (range 1–37). 32 patients received at least one dose of CNTO328 in combination with T and are evaluable. Baseline patient characteristics included: median PSA of 59 ng/mL (range 12–1430) and median CRP was 3.85 mg/L (range <1 to 91.3). One DLT was observed in each cohort (grade 4 neutropenic infection, grade 3 syncope and dehydration, grade 3 GI bleeding), though MTD for the combination was not reached. Most frequent ≥grade 3 adverse events (AE) were neutropenia (69%); leukopenia (63%); lymphopenia (31%); dyspnea (19%); fatigue (16%). One patient died due to AE (sepsis) reported as possible related to T and unlikely related to CNTO328 by investigator. Preliminary data show CNTO328 does not appear to have a major effect on T PK. Preliminary efficacy data is shown in the table . Ongoing evaluation indicates 3/12 partial responses in patients with measurable disease reported thus far. Conclusions: CNTO328 with T is well tolerated and demonstrates biological and clinical activity in CRPC that warrants further study. [Table: see text] [Table: see text]

Randomized Phase II Study of Docetaxel and Prednisone With or Without OGX-011 in Patients With Metastatic Castration-Resistant Prostate Cancer

2010 ◽  
Vol 28 (27) ◽  
pp. 4247-4254 ◽  
Author(s):  
Kim N. Chi ◽  
Sebastien J. Hotte ◽  
Evan Y. Yu ◽  
Dongsheng Tu ◽  
Bernhard J. Eigl ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Group Performance ◽  
Performance Status ◽  
Objective Response ◽  
Eastern Cooperative Oncology Group ◽  
Specific Antigen ◽  
Experimental Therapy ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Purpose To determine the clinical activity of OGX-011, an antisense inhibitor of clusterin, in combination with docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 1:1 to receive docetaxel/prednisone either with (arm A) or without (arm B) OGX-011 640 mg intravenously weekly. The primary end point was the proportion of patients with a prostate-specific antigen (PSA) decline of ≥ 50% from baseline, with the experimental therapy being considered of interest if the proportion of patients with a PSA decline was more than 60%. Secondary end points were objective response rate, progression-free survival (PFS), overall survival (OS), and changes in serum clusterin. Results Eighty-two patients were accrued, 41 to each arm. OGX-011 adverse effects included rigors and fevers. After cycle 1, median serum clusterin decreased by 26% in arm A and increased by 0.9% in arm B (P < .001). PSA declined by ≥ 50% in 58% of patients in arm A and 54% in arm B. Partial response occurred in 19% and 25% of patients in arms A and B, respectively. Median PFS and OS times were 7.3 months (95% CI, 5.3 to 8.8 months) and 23.8 months (95% CI, 16.2 months to not reached), respectively, in arm A and 6.1 months (95% CI, 3.7 to 8.6 months) and 16.9 months (95% CI, 12.8 to 25.8 months), respectively, in arm B. Baseline factors associated with improved OS on exploratory multivariate analysis were an Eastern Cooperative Oncology Group performance status of 0 (hazard ratio [HR], 0.27; 95% CI, 0.14 to 0.51), presence of bone or lymph node metastases only (HR, 0.45; 95% CI, 0.25 to 0.79), and treatment assignment to OGX-011 (HR, 0.50; 95% CI, 0.29 to 0.87). Conclusion Treatment with OGX-011 and docetaxel was well tolerated with evidence of biologic effect and was associated with improved survival. Further evaluation is warranted.

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