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A Randomized Phase II Study of OGX-011 in Combination with Docetaxel and Prednisone or

Docetaxel and Prednisone Alone in Patients with Metastatic Castration Resistant Prostate Cancer

Authors: Chi K, Hotte S, Yu E, Tu D, Eigl B, Tannock I, Saad F, North S, Powers J, E. Eisenhauer.Reviewed by: Dr. Stephanie Snow and Dr. Lori WoodAbstract: 5012Date posted: June 2009

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RTreatment A:

OGX-011 640 mg IV q week + Docetaxel 75 mg IV q3weeks + Prednisone 5 mg po bid

Note: Patients received three loading doses of OGX-011 the week prior to starting Docetaxel

Treatment B:

Docetaxel 75 mg IV q3weeks + Prednisone 5 mg po bid

Progressing, MetastaticCastration Resistant

Prostate Cancer

PSA ≥ 5ECOG 0-2

Chemo naïven=82

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RESULTS

Treatment

A

Treatment

Bp-value

1° Endpoint: Response Rate (%)

↓PSA ≥50%58 54 NS

PFS/TTP (median, mos)

7.26 6.14 NS

OS

(median, mos)23.8 16.8 0.06

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STUDY COMMENTARY: What is OGX-011?

• OGX-011 (aka Custirsen) is an anti-sense molecule complementary to clusterin mRNA

•Clusterin is a chaperone protein which stabilizes cells under stress:

• Anti-apoptotic secretory form

• Expressed in many cancers. In prostate cancer:

• increased expression correlated with Gleason grade

• increased expression seen after hormonal treatment

• Chemotherapy can induce expression, thereby leading to drug resistance

• Down regulation may lead to increased treatment sensitivity

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STUDY COMMENTARY

• Primary Endpoint was PSA response rate and there was no difference

• Mean number of cycles: Group A = 9, Group B = 7

• Discontinued treatment due to AEs: Group A = 9%, Group B = 5% (possibly due to more cycles?)

• Group A had more lymphopenia (no associated increase in infections), infusion reactions (usually during loading doses) and newly elevated Creatinine from baseline (20% vs 5%)

•Discontinued treatment due to progression: Group A 7%, Group B 16%

• It was designed to be a non-comparative trial, but OS data intriguing (Group A 23.8 m, Group B 16.8 m)

• Given the study met the primary endpoint of ≥ 50% reduction in PSA in Group A and the intriguing survival data, there are plans for a Phase III comparative trial

• Correlative study showed a decrease in serum clusterin during cycle 1 consistent with a treatment response

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BOTTOM LINE FOR CANADIAN MEDICAL ONCOLOGISTS

• Canadian trial from bench to bedside

• Combination makes biological sense

• Relatively well tolerated

• Phase III trial will be coming to a Canadian center near you!