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: 17.0 Level: PT Classification code 10005084 Term: Bladder transitional cell carcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Product Code: OGX-427
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: Not applicable
CAS Number: 915443-09-3
Current Sponsor code: OGX-427
Concentration unit: mg/ml milligram(s)/millil
Sponsors
OncoGenex Technologies, Inc.
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Age = 18 years at the time of consent. 2) Histologically documented metastatic or locally inoperable advanced TCC of the urinary tract (bladder, urethra, ureter and renal pelvis) (T4b, N2, N3 or M1 disease). 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. 3) Measurable disease defined as at least one target lesion that has not been irradiated and can be accurately measured in at least one dimension by RECIST 1.1 criteria. 4) No prior systemic chemotherapy with the following exceptions: • Prior use of radiosensitizing single agent therapy is allowed. • 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. 5) Minimum of 21 days have elapsed since prior major surgery or radiation therapy, with recovery from any adverse events. 6) Karnofsky performance status =70%. 7) Required laboratory values at baseline: • ANC = 1.5x10^9 cells/L • platelet count = 125 x 10^9/L • Calculated creatinine clearance =60 mL/minute (by modified Cockcroft-Gault formula). • bilirubin = 1.5 x ULN (= 2.5 x ULN if secondary to Gilbert’s disease) • AST and ALT = 3.0 x ULN 8) If of child-bearing potential, willing to use contraceptive measures during and for 3 months after completion of therapy. 9) willing to give written informed consent Are the trial subjects under 18? no Number of subjects for this age range: 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
Exclusion criteria: 1) A candidate for potential curative surgery or radiotherapy. 2) Intravesical therapy within the last 3 months, 3) Documented brain metastasis or carcinomatous meningitis, treated or untreated. NOTE: Brain imaging is not required unless the patient has symptoms or physical signs of CNS disease. 4) Peripheral neuropathy =Grade 2. 5) Known serious hypersensitivity to gemcitabine, cisplatin or carboplatin. 6) Current serious, uncontrolled medical condition such as congestive heart failure, angina, hypertension, arrhythmia, diabetes mellitus, infection, etc. or any condition such as a psychiatric illness which in the opinion of the investigator would make the patient unacceptable for the protocol. 7) Cerebrovascular accident, myocardial infarction or pulmonary embolus within 6 months of randomization. 8) 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. 9) Pregnant or nursing (must have a negative serum or urine pregnancy test within 72 hours prior to randomization). 10) Participating in a concurrent clinical trial of an experimental drug, vaccine or device. Participation in an observational study is allowed.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. ;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 Objective: • To compare the safety and tolerability of placebo, 600 mg of OGX-427, and 1000 mg of OGX-427 in combination with gemcitabine plus cisplatin. • To select the optimal dose of OGX-427 (600 mg vs. 1000 mg) for Phase 3 studies based on the safety and efficacy (i.e., risk/benefit). • To compare ORR (CR+PR), disease control rate (CR+PR+stable disease), 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 (CTC) 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. | — |
Secondary
| Measure | Time frame |
|---|---|
| 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 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. | — |
Countries
Canada, France, Germany, Italy, Poland, Spain, United States
Contacts
Public ContactMonica Krieger
OncoGenex Technologies, Inc.
Outcome results
None listed