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. El estudio está diseñado para determinar la eficacia de OGX-427 vS placebo en combinación con Gemcitabina y Cisplatino en pacientes con cancer en tracto urinario

• Register: EUCTR
• Last refreshed on: 19 January 2015
• Main ID: EUCTR2011-002424-41-ES
• Date of registration: 28/10/2011
• Prospective Registration: Yes
• 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. El estudio está diseñado para determinar la eficacia de OGX-427 vS placebo en combinación con Gemcitabina y Cisplatino en pacientes con cancer en tracto urinario
• 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 Estudio fase 2, doble ciego y aleatorizado para comparar la gemcitabina y el cisplatino en combinación con OGX-427 o placebo en pacientes con carcinoma de células transicionales avanzado
• Date of first enrolment: 08/02/2012
• 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, France, Germany, Italy, Poland, Spain, United States

Contacts

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

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

Key inclusion & exclusion 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:
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) History of significant bleeding disorder or recent bleeding event within 3 months of randomization or currently receiving warfarin anticoagulation therapy
9) 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.
10) Pregnant or nursing (must have a negative serum or urine pregnancy test within 72 hours prior to randomization).
11) Participating in a concurrent clinical trial of an experimental drug, vaccine or device. Participation in an observational study is allowed.


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

Health Condition(s) or Problem(s) studied

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

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)

Intervention(s)

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)/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.

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.

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

Secondary Objective: ?Comparar seguridad y tolerabilidad de placebo, 600 mg de OGX-427 y 1000 mg de OGX-427 combinado con gemcitabina y cisplatino.
?Seleccionar dosis óptima de OGX-427 (600 mg vs. 1000 mg) para estudios en Fase 3 en base a la seguridad y eficacia ( riesgo/beneficio).
?Comparar la TRG (RC+RP), tasa de control de enfermedad (RC+RP+enfermedad estable)duración de la respuesta y SLP entre brazos.
?Evaluar el efecto de la terapia con gemcitabina, cisplatino y OGX-427 sobre los valores séricos de Hsp27, de clusterina y cifras de CTC.
?Evaluar y comparar el número de células tumorales circulantes (CTC) en el inicio del estudio, la cifra mínima de CTC durante el tratamiento y el cambio máximo en la cifra de CTC en t entre brazos.
?Evaluar efecto administración repetida de OGX-427 sobre Cmax y Cmin mínimas de OGX-427 sericas.
?Evaluar la pérdida, translocación o deleción de PTEN, junto con genes dianas, en relación a la respuesta clínica y cambios en los niveles de clusterina y Hsp27.

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.