The trial is designed to determine the efficacy of OGX-427 Vs placebo in combination with Gemcitabine and Cisplatin in patients with Urinary tract cancer.

• Register: EUCTR
• Last refreshed on: 14 September 2015
• Main ID: EUCTR2011-002424-41-IT
• Date of registration: 03/04/2012
• Prospective Registration: No
• Primary sponsor: ONCOGENEX TECHNOLOGIES INC
• Public title: The trial is designed to determine the efficacy of OGX-427 Vs placebo in combination with Gemcitabine and Cisplatin in patients with Urinary tract cancer.
• Scientific title: A Randomized, Double-blind Phase 2 Study Comparing Gemcitabine and Cisplatin in Combination with OGX-427 or Placebo in Patients With Advanced Transitional Cell Carcinoma
• Date of first enrolment: 08/03/2012
• Target sample size: 180
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002424-41
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: yes Randomised: yes Open: no Single blind: no Double blind: yes Parallel group: no Cross over: no Other: no If controlled, specify comparator, Other Medicinial Product: no Placebo: yes Other: no Number of treatment arms in the trial: 3

Countries of recruitment

Canada, Germany, Italy, Spain, United States

Contacts

• Name: Monica Krieger
• Affiliation: OncoGenex Technologies Inc.

• Name: Monica Krieger
• Affiliation: OncoGenex Technologies Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
• Histologically documented metastatic or locally inoperable, advanced (T4b, N2, N3 or M1) TCC of the urinary tract (bladder, urethra, ureter and renal pelvis)
NOTE: Certain mixed histologies that are predominately (= 50%) TCC are eligible: squamous, adenocarcinoma, and undifferentiated. Mixed undifferentiated histology requires IHC consistent with a TCC origin. Mixed small-cell histologies are excluded.
• Measurable disease according to RECIST 1.1.
• No prior systemic chemotherapy with the following exceptions:
o Prior history of radiosensitizing single agent therapy is allowed.
o Prior neoadjuvant and adjuvant systemic chemotherapy are permissible if the interval from the end of therapy to the diagnosis of metastatic disease is at least 12 months.
• Karnofsky performance status =70%.
• Required laboratory values at baseline:
o ANC = 1.5 x 109 cells/L and platelet count = 125 x 109/L.
o calculated creatinine clearance =60 mL/minute according to the modified Cockcroft-Gault formula.
o bilirubin = 1.5 x ULN; AST and ALT = 3.0 x ULN.
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 150
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion criteria:
• A candidate for potential curative surgery or radiotherapy.
• Intravesicular therapy within the past 3 months.
• Documented brain metastasis or carcinomatous meningitis, treated or untreated.
• Peripheral neuropathy =Grade 2.
• Cerebrovascular accident, myocardial infarction, or pulmonary embolus within 6 months of randomization.
• Active second malignancy (except non-melanomatous skin cancer): active secondary malignancy is defined as a current need for cancer therapy or a high possibility (>30%) of recurrence during the study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Metastatic or locally inoperable, advanced (T4b, N2, N3 or M1) transitional cell carcinoma (TCC) of the urinary tract (bladder, urethra, ureter and renal pelvis)
MedDRA version: 14.1 Level: PT Classification code 10005084 Term: Bladder transitional cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Therapeutic area: Diseases [C] - Cancer [C04]

Intervention(s)

Product Name: OGX-427
Product Code: NA
Pharmaceutical Form: Solution for infusion
CAS Number: 915443-09-3
Current Sponsor code: OGX-427
Concentration unit: mg/ml milligram(s)/millilitre
Concentration type: equal
Concentration number: 25-
Pharmaceutical form of the placebo: Solution for infusion
Route of administration of the placebo: Intravenous use

Primary Outcome(s)

Main Objective: To ascertain whether there is evidence of longer survival relative to the
control arm for three comparisons: 600 mg OGX-427 Arm to control Arm;
1000 mg OGX-427 Arm to control Arm; and pooled 600 mg and 1000 mg
OGX-427 Arms to control Arm.

Primary end point(s): The primary efficacy endpoint for each patient is overall survival time.

Secondary Objective: • To compare safety and tolerability of placebo, 600 mg of OGX-427,
and 1000 mg of OGX-427 in combination with gemcitabine+cisplatin
• To select the optimal dose of OGX-427 for Phase 3 studies based on the safety and efficacy
• To compare ORR, disease control rate, duration of response and PFS between the arms
• To evaluate the effect of therapy with gemcitabine, cisplatin and OGX-
427 on serum Hsp27 levels, serum clusterin levels and CTC counts
• To evaluate and compare the number of circulating tumor cells at baseline, the minimum CTC count during treatment and the maximum
change in CTC count over time between arms
• To evaluate the effect of repeat OGX-427 dosing on serum OGX-427
Cmax and trough levels
• To evaluate for PTEN loss, translocation, or deletion, along with
downstream targets, in correlation with clinical response and changes in
clusterin and Hsp27 levels

Timepoint(s) of evaluation of this end point: The primary efficacy endpoint for each patient is overall survival time
measured as time from the date of randomization to the date of death
from any cause. For patients still alive at the time of analysis, overall
survival time will be censored on the date of last contact.

Secondary Outcome(s)

Secondary end point(s): The secondary efficacy objectives include evaluating the following:
• Best response to therapy (CR, PR, SD, PD) will be summarized by
treatment arm. In addition, the number (%) of patients with an overall
response (CR or PR) and with disease control (PR or CR or SD) will be
reported. Duration of responses will also be summarized.
• Progression-free survival time (PFS) will be summarized by treatment
arm. PFS is defined as the time from randomization to the date of
disease progression or death, whichever occurs first, before or after
treatment discontinuation. For those still on study and those who remain
alive and have not progressed after treatment discontinuation, PFS will
be censored on the date of the last tumor assessment.
• Serum Hsp27 levels, serum clusterin levels and CTC counts will be
summarized by treatment arm.
• Serum OGX-427 Cmax and trough levels will be summarized by
treatment arm.

Timepoint(s) of evaluation of this end point: Time from the date of randomization to the date of death from any cause
or the date of last contact for alive patients.

Secondary ID(s)

2011-002424-41-DE

OGX-427-02

Source(s) of Monetary Support

OncoGenex Technologies Inc.