The Borealis-2 Clinical Trial: A Randomized Phase 2 Study Comparing Docetaxel Alone to Docetaxel in Combination With OGX-427 in Patients With Relapsed or Refractory Metastatic Urothelial Carcinoma After Receiving a Platinum-containing Regimen: Hoosier Oncology Group GU12-160

Trial Information

The Borealis-2 Clinical Trial: A Randomized Phase 2 Study Comparing Docetaxel Alone to Docetaxel in Combination With OGX-427 in Patients With Relapsed or Refractory Metastatic Urothelial Carcinoma After Receiving a Platinum-containing Regimen: Hoosier Oncology Group GU12-160

OUTLINE: This is a multi-center study.

Eligible patients will be stratified based on time from prior systemic chemotherapy (< 3 vs
≥ 3 months) and Bellmunt prognostic factors criteria, which include Eastern Cooperative
Oncology Group (ECOG) performance status >0, hemoglobin <10g/dL, and presence of liver
metastases (0 versus 1-3 risk factors). Within the strata, participants will be randomly
assigned with equal probability to either the investigational arm (Arm A: docetaxel +
OGX-427) or the control arm (Arm B: docetaxel alone).

INVESTIGATIONAL ARM OGX-427 + DOCETAXEL (Arm A):

LOADING DOSE PERIOD:

Participants randomized onto the investigational arm (Arm A) will receive OGX-427 beginning
with a loading dose period prior to the initiation of docetaxel treatment. The first dose of
OGX-427 for the loading dose period must be administered within 5 working days of
registration and randomization.

During the loading dose period, participants will receive three separate administrations of
600 mg OGX-427 intravenously (IV) (days -9 to -1). There must be at least one "non-infusion"
day between each administration of OGX-427 (i.e., every other day) during the loading dose
period and between the third loading dose of OGX-427 and day 1 of cycle 1. There should be
no more than 7 days between the last loading dose and day 1 of cycle 1.

TREATMENT PERIOD:

During the treatment period, participants randomized to this arm will receive:

- OGX-427 600 mg IV weekly on days 1, 8, and 15 of each 21-day cycle. OGX-427 must be
administered prior to docetaxel on day 1 of each cycle.

- Docetaxel (75 mg/M2) IV on day 1 of each 21-day cycle. Docetaxel should be administered
immediately following the completion of the OGX-427 infusion.

OGX-427 MAINTENANCE:

Following completion of 10 cycles of docetaxel, 600 mg OGX-427 will continue to be
administered by IV weekly as maintenance therapy for participants who do not have disease
progression (i.e., stable disease or better). Participants without documented disease
progression who have discontinued from study treatment not due to toxicity related to
OGX-427 can also continue to receive OGX-427 maintenance as long as they have completed
disease assessments following at least 2 cycles of chemotherapy. Maintenance with OGX-427
will continue until disease progression or unacceptable toxicity.

CONTROL ARM - DOCETAXEL ALONE (Arm B):

TREATMENT PERIOD:

During the treatment period, participants randomized to this arm will receive:

- Docetaxel (75 mg/M2) IV on day 1 of each 21-day cycle. The first dose of docetaxel must be
administered within 5 working days of registration and randomization. Participants will
continue to receive docetaxel on day 1 of each 21-day cycle until disease progression,
unacceptable toxicity related to docetaxel, voluntary patient withdrawal, or a maximum of 10
docetaxel cycles.

FOLLOW-UP FOR BOTH ARMS:

Imaging studies will be performed every 6 weeks (i.e., after completion of cycles 2, 4, 6, 8
and 10) until disease progression and with any sign or symptom of new or worsening disease;
computed tomography scan (CT) of chest/abdomen/pelvis is preferred but magnetic resonance
imaging scan(MRI) is acceptable, especially for participants with increased risk of
contrast-related nephropathy or other contraindications. For Arm A, scans will be performed
every 2 cycles (6 weeks) +/1 week during the 21-day cycles of docetaxel administration and
every 6 weeks during maintenance OGX-427 administration until disease progression; for Arm
B, scans will be performed every 6 weeks during the 21-day cycles of docetaxel
administration until disease progression. All scans should be completed before the
subsequent cycle is scheduled to begin. Bone scans will be repeated, if positive at
baseline, every 6 weeks during the first 4 cycles of treatment (i.e., at the end of cycles 2
and 4) and then every 12 weeks thereafter until disease progression (i.e., at the end of
cycle 8, at end of treatment, and during maintenance with OGX-427 [Arm A only]).

All participants will have an End of Treatment (EOT) visit when they discontinue study
treatment. All participants will be followed until documented disease progression.

Once disease progression is documented, participants will enter a survival follow-up period.
All participants must be followed for survival as the primary endpoint. During the survival
follow-up period, data will be collected every three months regarding further cancer
therapy, secondary malignancy, and survival status.

Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1

Life Expectancy: Greater than 3 months

Hematopoietic:

- Absolute neutrophil count(ANC)≥ 1,500/mcL

- Hemoglobin ≥ 8 g/dL

- Platelets ≥ 100,000/mcL

Hepatic:

- Bilirubin ≤ 1.1 x upper limit of normal (ULN) (≤ 2.0 x ULN if secondary to Gilbert's
disease)

- Aspartate transaminase (AST), serum glutamic oxaloacetic transaminase (SGOT)/alanine
transaminase (ALT), serum glutamic pyruvic transaminase (SGPT) ≤ 1.5 X institutional
ULN

Renal:

- Serum creatinine ≤ 1.5 x ULN

Cardiac:

- Symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or
myocardial infarction within 3 months of randomization.