Mature results of a randomized phase II study of OGX-011 in combination with docetaxel/prednisone versus docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5012-5012 ◽  
Author(s):  
K. N. Chi ◽  
S. J. Hotte ◽  
E. Yu ◽  
D. Tu ◽  
B. Eigl ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Cancer Society ◽  
Best Response ◽  
Randomized Phase Ii ◽  
Psa Response ◽  
Visceral Metastases

5012 Background: Clusterin is a cytoprotective chaperone protein associated with CRPC progression. OGX is a 2'-methoxyethyl antisense that potentiates chemotherapy in xenografts and inhibits clusterin expression at doses of <640 mg. Methods: Pts with CRPC and chemo-naive received docetaxel (DOC) 75mg/m2 q3w + OGX 640mg IV weekly + prednisone (Arm A) or DOC + prednisone (Arm B) in a single stage randomized phase II design. Primary endpoint was PSA response rate (RR). Progression-free survival (PFS) and overall survival (OS) were secondary endpoints. Planned sample size was 40/arm: Arm A the hypotheses (PSA RR<40% vs. >60%) could be tested at 10% β and 10% α, Arm B the true PSA RR could be estimated with half-width of the 90% CI<13% if PSA RR=40%. Results: 82 pts (41 Arm A, 41 Arm B) were randomized from 09/05–12/06. At this analysis time, all pts are off therapy and 49 have died. One pt was ineligible but included in ITT survival analysis. Baseline characteristics were similar: median age 69 (49–87), PSA >100 μg/L in 51%, Hgb ≥100 g/L in 98%, alk phos >ULN in 44%, LDH >ULN in 36%, ECOG performance status (PS) 0:1 in 51%:49%, bone/lymph node/visceral metastases in 69%/50%/28%. Median cycles for Arm A and B was 9 and 7. Adverse events associated with OGX included fatigue, fever, rigors, diarrhea and rash. Mean serum clusterin change on day 1 cycle 2 was -18% in Arm A and +8% in Arm B (p = 0.0005). PSA RR was 58% (Arm A) and 54% (Arm B). PSA declines at 12 weeks of any/>30%/>50% was observed in 87%/65%/45% (Arm A) and 68%/58%/34% (Arm B). PSA/objective disease progression as best response occurred in 0%/4% (Arm A), and 3%/17% (Arm B). PFS for Arms A and B was 7.3 (5.3–8.8) and 6.1 months (3.7–8.6). Median OS for Arms A and B was 27.5 (19.2-∞) and 16.9 months (12.7–26.0) (unadjusted HR = 0.60 [0.34–1.06], p = 0.07). Variables predictive of OS on multivariate analysis: PS 0 vs 1 (p = 0.0002), presence of visceral metastasis (p = 0.006) and treatment assignment (HR = 0.54 [0.29–0.97], p = 0.04). Conclusions: The PSA RR in both arms met criterion for further study. OGX reduced serum clusterin and OS appears superior with DOC/OGX. This combination warrants further evaluation. Supported by a grant from the NCI-Canada/Canadian Cancer Society. [Table: see text]

A randomized phase II study of OGX-011 in combination with docetaxel and prednisone or docetaxel and prednisone alone in patients with metastatic hormone refractory prostate cancer (HRPC)

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 5069-5069 ◽  
Author(s):  
K. N. Chi ◽  
S. J. Hotte ◽  
E. Yu ◽  
B. J. Eigl ◽  
I. Tannock ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Serum Levels ◽  
Ecog Performance Status ◽  
Cancer Society ◽  
Randomized Phase Ii ◽  
Psa Response ◽  
Hormone Refractory ◽  
Metastatic Sites ◽  
Clusterin Expression

5069 Background: Clusterin, a cytoprotective chaperone protein that promotes cell survival, is associated with androgen independent progression and overexpressed in HRPC. OGX-011 (OGX, developed by OncoGenex Technologies/Isis Pharmaceuticals) is a 2’- methoxyethyl modified phosphorothioate antisense that inhibits clusterin expression in humans at doses of ≤640 mg and potentiates chemotherapy activity in prostate xenografts. The objective of this study was to determine the anti-tumor activity of OGX in combination with docetaxel (DOC) in patients (pts) with HRPC. Methods: Chemo-naive pts with metastatic HRPC were randomized to receive DOC 75mg/m2 q3 weeks + OGX 640mg weekly as a 2-hour IV infusion (Arm A) + prednisone or DOC + prednisone (Arm B). Serum levels of clusterin were assessed serially. A single stage randomized phase II design was employed with PSA response rate (RR) as the primary endpoint (Bubley et al, J Clin Oncol 1999;17:3461). Planned sample size was 40 per arm: Arm A the hypotheses (H0:PSA RR<40% vs. H1:PSA RR>60%) could be tested at 10% β and 10% a, Arm B the true PSA RR could be estimated with half-width of the 90% confidence interval <13% if observed PSA RR was 40%. Results: 82 pts (41/arm) were enrolled from September 2005 to December 2006 at 12 centers. Baseline characteristics are similar in both arms (available to date for 63 pts): median age 67 (range: 49–84), PSA 110 μg/L (5.6–1261), hemoglobin 128 g/L (96–158), alkaline phosphatase 133 U/L (47–1294), LDH 193 U/L (120–741). ECOG performance status was 0 in 49% and 1 in 51%; 67% had bone/nodal disease only and 33% had other metastatic sites. To date, 56 pts have received ≥2 cycles. Toxicity due to OGX included grade 1/2 fevers and rigors in 37% and 67% pts respectively, but other adverse events were similar in both arms. PSA response has occurred in 43%, progression in 9%, and 48% have not yet met criteria for response or progression. Conclusions: Combined docetaxel and OGX is well tolerated in pts with metastatic HRPC and PSA responses have been observed. Pt treatment, follow-up and analysis of serum clusterin levels continue. Results by arm will be available by June 2007. Supported by a grant from the NCI-Canada/Canadian Cancer Society. No significant financial relationships to disclose.

A phase Ib/II trial of indomethacin and enzalutamide to treat castration-resistant prostate cancer (CRPC).

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. TPS394-TPS394 ◽  
Author(s):  
Chong-xian Pan ◽  
Primo Lara ◽  
Christopher P. Evans ◽  
Mamta Parikh ◽  
Ralph de Vere White ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Trial ◽  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Phase Ib ◽  
Androgen Synthesis ◽  
Psa Response

TPS394 Background: Enzalutamide (Enza) and abiraterone (Abi) are commonly used to treat CRPC. Resistance is the most common cause of treatment failure. We discovered that a critical steroidogenic enzyme AKR1C3 was significantly elevated and contributed to intratumoral androgen synthesis in Enza-resistant prostate cancer cells and tumors. Overexpression of AKR1C3 induced androgen receptor variant 7 (AR-V7) expression, while inhibition of AKR1C3 downregulated AR-V7. We then discovered that indomethacin (Indo) inhibited AKR1C3 activation and sensitized resistant CRPC cells to Enza and Abi. One patient accidentally took Indo and achieved biochemical as well as radiological response of his prostate cancer. These findings prompted us to design a clinical trial to test the combination of Indo with Enza for the treatment of CRPC and to study the underlying mechanisms of action and resistance. Methods: This investigator-initiated single-arm Phase Ib/II trial enrolls patients with progressive CRPC after Abi, adequate vital organ function, ECOG performance status 0-2, and serum testosterone < 50 ng/dl. Major exclusion criteria include prior Enza treatment, brain metastasis and history of seizure. In the Phase Ib cohort, patients receive Enza 160 mg po qd and Indo 50 mg po tid to determine toxicity. The Phase II expansion will enroll 26 patients with 21 evaluable patients. This sample size provides 90% power to detect, at the 0.05 level (1-sided), the difference between a PSA response rate of 50% expected with the study treatment and a historical control of 20% with Enza alone. Co-primary endpoints are safety and PSA response of ≥50% decrease. Secondary endpoints include overall response rate as determined by the Prostate Cancer Working Group 2 criteria (PCWG2), progression-free survival and overall survival. Molecular correlative studies are exploratory endpoints. Serum and intratumoral androgen levels, full-length AR, AR-V7 and AKR1C3 will be measured to assess the effect of the combination therapy. To date, 4 patients have been enrolled to the trial (clinicaltrials.gov Identifier No: NCT02935205; this trial is funded by DoD Prostate Cancer Research Program IMPACT award). Clinical trial information: NCT02935205.

TheraP: A randomised phase II trial of 177Lu-PSMA-617 (LuPSMA) theranostic versus cabazitaxel in metastatic castration resistant prostate cancer (mCRPC) progressing after docetaxel: Initial results (ANZUP protocol 1603).

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 5500-5500 ◽  
Author(s):  
Michael S Hofman ◽  
Louise Emmett ◽  
Shahneen Kaur Sandhu ◽  
Amir Iravani ◽  
Anthony M. Joshua ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Progression Free Survival ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Randomized Phase Ii ◽  
Pet Ct ◽  
Psa Response ◽  
Psa Progression ◽  
Fdg Pet Ct

5500 Background: LuPSMA is a radiolabeled small molecule that delivers therapeutic β-radiation to PSMA-expressing tumors. Encouraging efficacy and safety has been shown in non-randomized studies of mCRPC. TheraP is a randomized phase II trial comparing LuPSMA vs cabazitaxel in men with mCRPC progressing after docetaxel. Methods: Men with mCRPC, and imaging with 68Ga-PSMA-11 and 18F-FDG PET/CT that confirmed high PSMA-expression and no sites of FDG-positive/PSMA-negative disease, were randomly assigned (1:1) to LuPSMA (6-8GBq q6weeks up to 6 cycles) vs cabazitaxel (20mg/m2 q3weeks up to 10 cycles); stratified by disease burden (>20 vs ≤20 sites), prior novel antiandrogens (NAA; abiraterone or enzalutamide), and study site. The primary endpoint was PSA response rate (PSA50-RR) defined by ≥50% reduction. Secondary efficacy endpoints included PSA-progression-free survival (PSA-PFS) and overall survival (OS). Data cut-off was 31DEC19 at this first pre-specified analysis. Results: 200 (median age 72 y, prior NAA 91%, >20 lesions 78%) of 291 PET screened men were randomised to LuPSMA (N=99) or cabazitaxel (N=101). 17 patients withdrew or died before receiving study treatment (1 LuPSMA vs 16 cabazitaxel). The PSA50-RR was higher in those assigned LuPSMA than cabazitaxel (65/99 [66%; 95%CI 56-75] vs 37/101 [37%; 95%CI 27-46]; P<0.001). At a median follow-up of 11.3 months, LuPSMA significantly improved PSA-PFS (HR 0.63, 95%CI 0.45-0.88, P=0.007; 143 events with next pre-specified analysis planned after 170 events). Efficacy results were similar when analyses were restricted to per-protocol treated men. OS data remains immature (57 deaths). Grade III-IV adverse events (AEs) occurred in 31/98 (32%) LuPSMA-treated men vs 42/85 (49%) in cabazitaxel-treated men. Discontinuations for toxicity occurred in 1/98 (1%) LuPSMA vs 3/85 (4%) cabazitaxel-treated. There were no treatment-related deaths. Conclusions: In men with docetaxel-treated mCRPC, LuPSMA was more active (PSA50-RR) than cabazitaxel with relatively fewer G3-4 AEs and PSA-PFS favoring LuPSMA. Clinical trial information: NCT03392428 .

SWOG S0354: A phase II trial of CNTO328, a monoclonal antibody against interleukin-6 (IL-6), in chemotherapy pretreated patients (pts) with castration- resistant prostate cancer (CRPC)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 5143-5143
Author(s):  
J. K. Pinski ◽  
B. Goldman ◽  
T. Dorff ◽  
P. Mack ◽  
P. Lara ◽  
...  
Keyword(s):  
Phase Ii ◽  
Performance Status ◽  
Progression Free Survival ◽  
Response Assessment ◽  
Castration Resistant Prostate Cancer ◽  
Plasma Cytokines ◽  
Cancer Cell Survival ◽  
Psa Response ◽  
Pleiotrophic Effects ◽  
Grade 3

5143 Background: IL-6 facilitates cancer cell survival via pleiotrophic effects on proliferation, apoptosis, angiogenesis, differentiation, and chemo-resistance. A multicenter phase II study of CNTO328 in chemo pretreated CRPC pts was conducted. Methods: Eligible pts had one prior chemotherapy, Zubrod performance status 0–2, and adequate end-organ function. Regimen: CNTO328 6 mg/kg IV q2 weeks x 12 cycles. Response assessment was q6 weeks. Primary endpoint was PSA response rate (RR) defined as ≥50% reduction. Accrual was completed in 2 stages, with planned accrual of 20 eligible pts in the first stage and 40 overall. Plasma cytokines were measured by Luminex in 44 pts. Results: Of 62 pts, 54 were eligible; all had received prior taxane therapy. Two (3.7%; 95% CI: 0.5%, 12.8%) had PSA response. Of 47 pts evaluable by RECIST, none had a response and 10 (21%) had stable disease (SD). With median follow-up of 6.6 months, median progression-free survival is 1.6 months (95% CI: 1.6, 1.7). Grade 4 toxicity included 1 case of DIC and 1 CNS ischemia; grade 3 toxicities included elevated AST (1), gastritis/esophagitis (2), thrombocytopenia (2), pain (2), leucopenia (1), and neuropathy (2). Median baseline IL-6 levels were 12.5 pg/mL (IQR: 2.5, 41.5). Pts with levels >12.5 pg/mL had worse 6-month survival vs. < 12.5 pg/mL (53% vs 94%, p = 0.02). Post-cycle 1, IL-6 levels were > 250-fold higher, indicating antibody-target complex formation. 33/39 pts had a decline in C-reactive protein (CRP) plasma levels at 6 weeks. Conclusions: CNTO328 was well-tolerated and resulted in a PSA RR of 3.7% and RECIST SD rate of 21%. Declining CRP levels during treatment reflect biologic activity. Elevated baseline IL-6 levels portend a poor prognosis. Additional translational studies will be presented. Additional study of CNTO328 in combination may be warranted. [Table: see text]

ARN-509 in men with high-risk nonmetastatic castration-resistant prostate cancer (CRPC).

2013 ◽  
Vol 31 (6_suppl) ◽  
pp. 7-7 ◽  
Author(s):  
Matthew Raymond Smith ◽  
Emmanuel S. Antonarakis ◽  
Charles J. Ryan ◽  
William R. Berry ◽  
Neal Shore ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Phase I ◽  
Phase Ii ◽  
Nuclear Translocation ◽  
Performance Status ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Psa Response ◽  
Psa Progression

7 Background: ARN-509 is a novel second-generation anti-androgen that binds directly to the ligand-binding domain of the androgen receptor, impairing nuclear translocation and DNA binding. The Phase II portion of a multicenter Phase I/II study is evaluating the activity of ARN-509 in 3 distinct patient populations of men with CRPC (high risk non-metastatic CRPC, metastatic treatment-naïve CRPC, and progressive disease after abiraterone acetate). Preliminary results for the cohort of patients with high-risk non-metastatic CRPC are presented here. Methods: All patients had CRPC, no radiographic evidence of metastases (pelvic lymph nodes <3 cm below the iliac bifurcation were allowed), and high risk for disease progression based on PSA value ≥ 8 ng/mL within 3 months of enrollment and/or PSA doubling time ≤ 10 months. Patients received ARN-509 at the recommended Phase II dose of 240 mg/day, previously established in Phase I (Rathkopf et al, GU ASCO 2012). The primary endpoint was PSA response rate at 12 weeks according to the Prostate Cancer Working Group 2 Criteria. Secondary endpoints included safety, time to PSA progression and 1-year metastasis-free survival. PSA assessments were collected every 4 weeks and tumor scans were performed every 16 weeks. Results: Forty-seven patients were enrolled between November 2011 and May 2012. The median age was 71 years (range 51 to 88) and at baseline, patients presented with ECOG performance status 0 (77%), Gleason Score 8-10 (32%), and median PSA of 10.7 ng/mL. All patients received prior treatment with a LHRH analog with or without a first-generation anti-androgen. At a median treatment duration of 20 weeks, three patients discontinued the study. The most common treatment-related adverse events (AE) were fatigue (30%), diarrhea (28%), nausea (17%), rash (13%), and abdominal pain (11%). The incidence of Grade 3 AEs was 6.4%, and no seizures have been observed to date. The 12-week PSA response was 91% and the time to PSA progression has not been reached. Conclusions: In men with high-risk non-metastatic CRPC, ARN-509 is safe and well tolerated with promising preliminary activity based on high PSA response rates. Clinical trial information: NCT01171898.

Efficacy of docetaxel and prednisone in men with metastatic castration-resistant prostate cancer (mCRPC) exposed to prior ketoconazole (KC).

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 204-204
Author(s):  
Gregory Russell Pond ◽  
Andrew J. Armstrong ◽  
Brian A. Wood ◽  
Lance Howard Leopold ◽  
Matt D. Galsky ◽  
...  
Keyword(s):  
Performance Status ◽  
Objective Response ◽  
Clinical Importance ◽  
Progression Free Survival ◽  
Abiraterone Acetate ◽  
Castration Resistant Prostate Cancer ◽  
Androgen Synthesis ◽  
Randomized Phase Ii ◽  
Psa Response ◽  
And Performance

204 Background: The efficacy of docetaxel following exposure to androgen synthesis inhibitors such as KC or abiraterone acetate (AA) is unknown. Given the emerging use of pre-docetaxel AA and docetaxel’s inhibition of androgen signaling, we retrospectively evaluated the efficacy of every 3 week docetaxel with prednisone (DP) in mCRPC previously exposed to KC as compared to KC-naïve patients. Methods: A randomized phase II trial of men with mCRPC treated with DP+AT-101 (bcl-2 inhibitor) vs. DP+placebo was analyzed (stratified for pain and performance status). Both arms were combined for analysis as no significant differences were seen. Overall survival [OS], progression-free survival [PFS], objective response [ORR], pain and PSA response rates were estimated with and without prior KC. Results: Of 220 evaluable men, 40 (18.2%) received prior KC (median duration=2.0 months, maximum=31.1 months). These 40 men had less visceral disease (15% vs 28%), more prior radiotherapy (70% vs 51%), and increased prior radiological (38% vs 21%) or bone scan progression (55% vs 41%). Efficacy outcomes were not statistically different (table). After adjusting for baseline stratum and treatment group, prior KC did not appear to significantly change OS with DP-based therapy (HR 1.34, 95%CI: 0.86–2.09, p=0.20). Conclusions: Similar outcomes were observed in mCRPC treated with DP-based therapy with or without prior KC. Given the marginally inferior survival with prior KC, evaluation of docetaxel outcomes following AA is of clinical importance, given its more potent CYP17 inhibition. [Table: see text]

PEAK (study 20070509): A randomized phase II study of mFOLFOX6 with either panitumumab (pmab) or bevacizumab (bev) as first-line treatment (tx) in patients (pts) with unresectable wild‑type (WT) KRAS metastatic colorectal cancer (mCRC).

2013 ◽  
Vol 31 (4_suppl) ◽  
pp. 446-446 ◽  
Author(s):  
Lee Steven Schwartzberg ◽  
Fernando Rivera ◽  
Meinolf Karthaus ◽  
Gianpiero Fasola ◽  
Jean-Luc Canon ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Study ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Phase Iii ◽  
Ecog Performance Status ◽  
Eligibility Criteria ◽  
Prior Therapy ◽  
Randomized Phase Ii

446 Background: Pmab has demonstrated significant improvement in progression-free survival (PFS) in pts with WT KRAS mCRC as 1st-line tx in a phase III trial comparing pmab + FOLFOX4 vs FOLFOX4 alone. Here, we describe the results of PEAK, a multicenter, randomized phase II study evaluating pmab + mFOLFOX6 and bev + mFOLFOX6 in pts with previously untreated WT KRASmCRC. Methods: Pts were randomized 1:1 to pmab 6.0 mg/kg + mFOLFOX6 Q2W or bev 5.0 mg/kg + mFOLFOX6 Q2W. Pt eligibility criteria included: WT KRASmCRC, ECOG performance status ≤ 1, and no prior chemotherapy, anti-VEGF tx, or anti-EGFR tx for mCRC. The primary endpoint was PFS; secondary endpoints included overall survival (OS), objective response rate (ORR), and safety. No formal hypothesis was tested. Results: 285 pts with WT KRASmCRC were randomized and 278 pts received tx. Demographics were balanced between arms. Intent-to-treat efficacy results are shown (Table). Worst grade 3/4 adverse events (AE) occurred in 86% of pts in the pmab + mFOLFOX6 arm vs 76% of pts in the bev + mFOLFOX6 arm. Grade 5 AEs occurred in 5% of pts in the pmab + mFOLFOX6 arm and 6% of pts in the bev + mFOLFOX6 arm. Tx discontinuation due to any AE was 24% in the pmab + mFOLFOX6 arm and 27% in the bev + mFOLFOX6 arm. Conclusions: In this estimation study of pts with WT KRASmCRC without any prior therapy for mCRC, PFS and ORR were similar between arms. The median OS was not reached in the pmab + mFOLFOX6 arm. The safety profile for both arms was consistent with previously reported studies of either combination. Tx discontinuation rates due to AEs were similar between arms. Clinical trial information: NCT00819780. [Table: see text]

Clinical activity of enzalutamide against metastatic castration-resistant prostate cancer (mCRPC) in patients who have progressed on abiraterone acetate: The Princess Margaret experience.

2014 ◽  
Vol 32 (4_suppl) ◽  
pp. 159-159 ◽  
Author(s):  
Francisco Emilio Vera-Badillo ◽  
Raya Leibowitz-Amit ◽  
Arnoud Templeton ◽  
Jo-An Seah ◽  
Srikala S. Sridhar ◽  
...  
Keyword(s):  
Response Rate ◽  
Performance Status ◽  
Progression Free Survival ◽  
Median Number ◽  
Abiraterone Acetate ◽  
Clinical Activity ◽  
Castration Resistant Prostate Cancer ◽  
Ecog Performance Status ◽  
Psa Response ◽  
Metastatic Sites

159 Background: In men with mCRPC enzalutamide and abiraterone acetate have been shown individually to prolong survival after progression on chemotherapy with docetaxel. Little is known about the sequential use of enzalutamide and abiraterone. A PSA response rate of 8% and progression free survival (PFS) of 2.7 months has been reported for 38 men who received abiraterone following enzalutamide [Loriot, Ann Onc, 2013]. Here we report our experience with enzalutamide following abiraterone. Methods: We reviewed all patients with mCRPC treated with enzalutamide following abiraterone and docetaxel at our institution. Primary outcomes were PSA response rate (confirmed decline ≥ 50%) and time to treatment failure (TTF, defined as the time from treatment initiation to treatment discontinuation for any reason, including disease progression, treatment toxicity, patient preference, or death.). Data were analyzed using the Kaplan-Meier method. Results: Twenty-six patients were treated between August 2012 and July 2013. Median age was 72 years (range 56-88); 85% had ECOG performance status 0 or 1; metastatic sites included bone (N=25, 96%), lymph nodes (N=19, 73%) and visceral (N=1, 3.4%). Median number of prior cycles of docetaxel was 8 (range 1 – 12), 6 patients (29%) had previous exposure to ketoconazole, and median duration of previous abiraterone was 8.7 (range 1.4-22.7) months. Seven pts (27%) had a PSA response ≥ 50% and an additional 7 patients (27%) had a ≥ 30% PSA response. Median TTF on enzalutamide was 4.9 (95% CI 3.8-6.2) months. Reasons for discontinuation of enzalutamide were clinical and/or biochemical progression in 24 patients (92%), and toxicity (fatigue grade 3-4) in 3 patients (11.5%). An update of patient numbers and analysis will be presented at the meeting. Conclusions: Treatment of patients with mCRPC with enzalutamide after progression on docetaxel and abiraterone has modest clinical activity.

Randomized phase II study of maintenance vandetanib (ZD6474) in small cell lung cancer (SCLC) patients who have a complete or partial response to induction therapy: NCIC CTG BR.20

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 7522-7522 ◽  
Author(s):  
A. M. Arnold ◽  
M. Smylie ◽  
K. Ding ◽  
Y. Ung ◽  
B. Findlay ◽  
...  
Keyword(s):  
Partial Response ◽  
Phase Ii ◽  
Randomized Study ◽  
Progression Free Survival ◽  
P Value ◽  
Cancer Society ◽  
Randomized Phase Ii ◽  
Secondary Endpoints ◽  
Dose Modifications ◽  
Ecog Ps

7522 Background: Vandetanib (V) is an inhibitor of vascular endothelial and epidermal growth factor receptors. This trial sought to determine whether maintenance V, given after standard chemotherapy (CT) and radiation (RT), prolonged progression-free survival (PFS) in responding patients with SCLC. Secondary endpoints: overall survival (OS) and toxicity. Methods: Phase II randomized, study of V 300 mg PO daily or placebo (P). Eligibility: complete (CR) or partial response (PR) to platinum-based CT, ECOG PS 0–2 and completion of RT (thoracic or prophylactic cranial). Statistics: 80% power to detect a 2.5 months improvement in median PFS (estimate for P of 4 months) using a 1-sided 10% level test (100 eligible patients; 77 events). Results: Between May 2003 and March 2006, 107 patients were accrued from 17 centres. Median follow up: 13.5 months. 46 had limited disease (LD); 61 extensive disease (ED). There were fewer PS 0 patients (11 vs. 20), and fewer had CR to initial CT (4 vs. 8) in the V arm. V patients were more likely to experience toxicity and require dose modification. The most frequent toxicities leading to dose modifications were gastrointestinal and rash. Clinically asymptomatic QTc prolongation was observed in 8 V patients. 83 of 107 patients developed progressive disease (43 on V; 40 on P). The median PFS for V was 2.7 months (80% C.I.: 1.1 –4.5) and 2.8 months for P (80% C.I.: 1.9 –5.6); estimated hazard ratio (HR) was 1.01 for V vs P (80% C.I.: 0.75 –1.36, 1-sided P-value = 0.51). Median OS for V was 10.6 months vs. 11.9 months for P; HR was 1.43 for V vs. P (80% C.I.: 1.00 –2.05, 1-sided P-value = 0.90). In a planned subgroup analysis, a significant interaction was noted (P-value = 0.01); with LD patients randomized to V having a longer OS (HR: 0.45, 1-sided P-value = 0.07), whereas ED patients randomized to V had a shorter OS compared to P (HR: 2.27, 1-sided P-value = 0.996). Conclusion: V failed to demonstrate efficacy as maintenance therapy for SCLC. Future targeted therapies should probably be explored concurrently with chemotherapy. This study was supported by the Canadian Cancer Society and AstraZeneca. [Table: see text]

A randomized phase II trial of weekly docetaxel plus either cisplatin or oxaliplatin in patients with previously untreated advanced gastric cancer: Preliminary results

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 4566-4566
Author(s):  
S. Sym ◽  
S. Park ◽  
J. Park ◽  
K. Kwon ◽  
I. Jung ◽  
...  
Keyword(s):  
Phase Ii ◽  
Phase Ii Trial ◽  
Performance Status ◽  
Objective Response ◽  
Progression Free Survival ◽  
Tolerability Profile ◽  
Preliminary Results ◽  
Weekly Docetaxel ◽  
Randomized Phase Ii ◽  
Significant Difference

4566 Background: Docetaxel, in combination with cisplatin or oxaliplatin, has demonstrated efficacy against AGC. This randomized phase II trial evaluated two weekly docetaxel-based regimens to see which would be most promising according to objective response rate (ORR) as first-line therapy in AGC. Methods: Chemotherapy-naïve patients with measurable unresectable and/or metastatic gastric adenocarcinoma and a performance status ≤2 were randomly assigned to receive docetaxel (35 mg/m2) weekly on days 1 and 8 of a 21-day cycle plus either cisplatin (60 mg/m2 on day 1) (arm A) or oxaliplatin (120 mg/m2 on day 1) (arm B). Toxicity was assessed on days 1, 8, and 21 of each cycle, and response was evaluated every 2 cycles. Results: Between March 2007 and December 2008, 61 eligible patients entered. In Arm A, 29 patients were evaluable for objective response and 31 for safety. In Arm B, 28 patients were evaluable for objective response and 30 for safety. Median age was 52 years and disease status was comparable for both arms. Ten of 29 (34.5%) patients had a confirmed objective response in the arm A (95% confidence interval [CI] 17.1–51.8%) and 11 of 28 (39.2%) patients had a confirmed objective response in the arm B (95% CI 21.1- 57.2%). No significant difference was noted between the arms both for ORR (p=0.202) or for disease control (58.6% and 82.1%, respectively, p=0.082). Median progression free survival time was 4.4 month in the arm A and 4.3 months in the arm B (Hazard ratio = 0.936; 95% CI, 0.503–1.744; p = 0.836). There was no relevant difference in the occurrence of overall grade ¾ toxicity between the two arms (51.6% vs. 46.6%, respectively; p=0.800). Neutropenia was the most common grade 3/4 toxicity (32.3% vs. 36.6%, respectively). There was one treatment related death in Arm B. Conclusions: The preliminary results showed that both treatment arms have similar clinical efficacy as front-line treatment in AGC. Each regimen has a manageable tolerability profile. The accrual is ongoing. No significant financial relationships to disclose.

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