Clusterin: Review of research progress and looking ahead to direction in hepatocellular carcinoma

Table 1 Summary of the phase I clinical trials of custirsen

Clinical trial	Notes	Drugs	Patients, n	Phase
OGX-011-01[24]	Dose escalation, single-center study in patients receiving hormone therapy and custirsen prior to radical prostatectomy	Buserelin, custirsen sodium, flutamide	25	I
Hormone therapy and OGX-011 before radical prostatectomy in treating patients with prostate cancer (NCT00054106)
OGX-011-2[25]	Dose escalation, multi-center, study with custirsen in combination with docetaxel in patients with CRPC, NSCLC, breast, ovarian, bladder or renal cancer	Custirsen sodium, docetaxel	40	I
OGX-011 and docetaxel in treating patients with metastatic or locally recurrent solid tumors (NCT 00471432)
OGX-011-10	Open-label, one arm, one-sequence crossover drug-drug interaction study in advanced solid tumors subjects to evaluate the potential effect of custirsen on the pharmacokinetics of paclitaxel	Custirsen, paclitaxel and carboplatin	36	I
A clinical study in cancer patients to investigate the potential impact of custirsen on the blood levels of the chemotherapeutic drug, paclitaxel, when given together as part of a treatment regimen (NCT01497470)

Table 2 Summary of the phase II clinical trials of custirsen

Clinical trial	Notes	Drugs	Patients, n
OGX-011-3[26] Docetaxel and prednisone with or without OGX-011 in treating patients with recurrent or metastatic prostate cancer that did not respond to previous hormone therapy (NCT00258388)	Randomized, two-arm, open label, multi-center study in patients who received docetaxel/prednisone with/without custirsen	Custirsen sodium: 640 mg iv for 2 h-Cycle 1: days 7, 5, 3, 1, 8, 15 (4 wk cycle) Docetaxel: 75 mg/m2 iv for 1 h-day 1 every 3 wk (3 wk cycles) Prednisone: 5 mg PO bid	82
0GX-011-04 Hormone ablation therapy in patients with localized prostate cancer	A single-arm, open-label, single center study to assess the effects of combined hormone ablation therapy and weekly treatment with custirsen prior to surgical removal of the prostate gland	LHRH agonist (hormone ablation) was given with weekly custirsen treatment for 12 wk and prostatectomy performed within 14 d of the last dose of custirsen	24
OGX-011-05[28] A study of OGX-011/Gemcitabine/Platinum-based regimen in stage IIIB/IV non-small cell lung cancer (NCT00138658)	An open-label trial to assess the safety and anti-tumor effect of OGX-011 when given to patients in combination with GEM and CIS/CARB	Custirsen sodium: 640 mg iv for 2 h Cycle 1: days 7, 5, 3 and days 1, 8, 15 of every 21-d cycle GEM: days 1 and 8 Cisplatin/Carboplatin: day 1 6 cycle 2	81
OGX-011-06[29] OGX-011 and docetaxel in treating women with locally advanced or metastatic breast cancer (NCT00258375)	To study how well giving OGX-011 together with docetaxel works in treating women with locally advanced or metastatic breast cancer	Custirsen sodium: 640 mg iv for 2 h on days 7, 5, 3, 1, 8 and 15 of cycle 1 and on days 1, 8, 15 on the other cycle Docetaxel: 75 mg/m2 iv for 1 h on days 1 and 8	15
OGX-011-07[27] Evaluation of safety and feasibility of OGX-011 in combination with second line chemotherapy in patients with HRPC (NCT00327340)	A multicenter, open-label, randomized study evaluating the safety and feasibility of custirsen in combination with second line chemotherapy in patients with HRPC	Prednisone: 5 mg twice daily through completion of the final treatment cycle. Custirsen: 640 mg iv for 2 h on days 9 to 1 of every cycle Mitoxantrone: 12 mg/m2, iv on day 1. Docetaxel: 75 mg/m2, iv on day 1	42
Assessing the effects of combined therapy with androgen ablation and OGX-011 given prior to radical prostatectomy on pathologic complete response rates in men with localized prostate cancer and high risk features (NCT00138918)	An open-label, non-blinded, phase II clinical, tissue pharmacokinetic and pharmacodynamics study of weekly OGX-011 and neoadjuvant hormone therapy prior to radical prostatectomy in patients with localized prostate carcinoma and high risk features	Neoadjuvant hormone therapy: buserelin 9.9 mg subcutaneously × 1 injection with flutamide 250 mg orally tid for the first 4 wk OGX-011: 640 mg by intravenous infusion over 2 h on days 1, 3, and 5	45

Table 3 Summary of the phase III clinical trials of custirsen

Phase III trial	Treatment and Arms	Patients, n	Completion Date
ENSPIRIT A multinational, randomized, open-label study of custirsen in patients with advanced or metastatic non-small cell lung cancer (NCT01630733)	Arm A: Custirsen Docetaxel Custirsen: Three loading doses of custirsen 640 mg iv over 2 h administered in 5 to 9 d prior to day 1 of cycle 1, then custirsen 640 mg iv weekly every 21-d cycle Docetaxel: 75 mg/m2 iv over 1 h on day 1 of every 21-d cycle Arm B: Docetaxel Docetaxel: 75 mg/m2 iv over 1 h on day 1 of every 21-d cycle until disease progression, unacceptable toxicity, withdrawal of consent or protocol specified parameters to stop treatment	1100	July, 2017
AFFINITY	Drugs: cabazitaxel, prednisone, custirsen sodium	630	December, 2015
Comparison of cabazitaxel/prednisone alone or in combination with custirsen for second line chemotherapy in prostate cancer (NCT01578655)	Following 2 loading doses of custirsen (640 mg iv), cabazitaxel (25 mg/2 iv) is administered on a 3-wk cycle with weekly custirsen (640 mg iv) and daily prednisone (10 mg PO) until disease progression, unacceptable toxicity, or completion of 10 cycles Drugs: cabazitaxel, prednisone Cabazitaxel (25 mg/m2 iv) is administered on a 3-wk cycle with daily prednisone (10 mg PO) until disease progression, unacceptable toxicity, or completion of 10 cycles
SYNERGY Comparison of docetaxel/prednisone to docetaxel/prednisone in combination with OGX-011 in men with prostate cancer (NCT01188187)	Drugs: custirsen sodium, docetaxel, prednisone Docetaxel/prednisone on a 3-wk cycle with weekly OGX-011 640 mg infusions until disease progression, unacceptable toxicity, or completion of 10 cycles. Drugs: docetaxel, prednisone Docetaxel/prednisone on a 3-wk cycle until disease progression, unacceptable toxicity, or completion of 10 cycles	1023	April, 2014