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Trial record 1 of 1 for:    NCT01454089
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A Phase 2 Study Comparing Chemotherapy in Combination With OGX-427 or Placebo in Patients With Bladder Cancer

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborators:
OncoGenex Pharmaceuticals
PRA Health Sciences
Information provided by (Responsible Party):
OncoGenex Technologies
ClinicalTrials.gov Identifier:
NCT01454089
First received: October 5, 2011
Last updated: August 5, 2014
Last verified: August 2014
  Purpose

This study evaluates the safety and efficacy of standard chemotherapy in combination with the investigational drug OGX-427 in patients with advanced bladder cancer.


Condition Intervention Phase
Urologic Neoplasms
Metastatic Bladder Cancer
Urinary Tract Neoplasms
Drug: OGX-427 600 mg
Drug: OGX-427 1000 mg
Drug: Placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official 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

Resource links provided by NLM:


Further study details as provided by OncoGenex Technologies:

Primary Outcome Measures:
  • Overall survival [ Time Frame: From date of randomization to date of death from any cause (approx 12 months) ] [ Designated as safety issue: No ]
    To determine whether there is evidence of longer survival relative to the control arm for three comparisons: 600 mg OGX-427; 1000 mg OGX-427; and pooled 600 mg and 1000 mg OGX-427 arms. OS is defined as the time from randomization to death from any cause; OS will be censored on date of last contact for patients still alive at time of analysis.


Secondary Outcome Measures:
  • Safety summary [ Time Frame: During the trial until end of treatment visit (approx. 6-8 months) ] [ Designated as safety issue: Yes ]
    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; safety and tolerability will be evaluated based on the number (%) of patients experiencing abnormal laboratory test results and adverse events graded using National Cancer Institute's Common Terminology Criteria for Adverse Events (CTCAE) version 4.0.

  • Disease response/control [ Time Frame: During the trial and every 6 weeks during the follow up period (approx 10-12 months) ] [ Designated as safety issue: No ]
    To compare overall response rate (ORR), disease control rate, duration of response, and progression-free survival (PFS) between the arms. ORR is defined as the percent of patients with complete response (CR) or partial response (PR) as defined by RECIST; disease control rate is defined as the percent of patients with CR + PR + stable disease (SD); PFS is defined as the time from randomization to date of progression or death, whichever occurs first (censored on date of last tumor assessment for patients who have not progressed after treatment discontinuation).

  • Surrogate endpoint-Serum Hsp27 levels [ Time Frame: During the trial and every 6 weeks during the follow up period (approx 10-12 months) ] [ Designated as safety issue: No ]
    To evaluate the effect of therapy with gemcitabine, cisplatin, and OGX-427 on serum Hsp27 levels summarized by treatment arm

  • Surrogate Endpoint-Serum Clusterin Levels [ Time Frame: During the trial and every 6 weeks during the follow up period (approx 10-12 months) ] [ Designated as safety issue: No ]
    To evaluate the effect of therapy with gemcitabine, cisplatin, and OGX-427 on serum clusterin levels summarized by treatment arm

  • Surrogate endpoint-Circulating tumor cell count [ Time Frame: During the trial and every 6 weeks during the follow up period (approx 10-12 months) ] [ Designated as safety issue: No ]
    To evaluate the effect of therapy with gemcitabine, cisplatin, and OGX-427 on circulating tumor cell (CTC) counts summarized by treatment arm

  • Pharmacokinetics-serum OGX-427 Cmax [ Time Frame: During the trial and through the end of treatment visit (approx 6-8 months) ] [ Designated as safety issue: No ]
    To evaluate the effect of repeat OGX-427 dosing on serum OGX-427 Cmax summarized by treatment arm.

  • Pharmacokinetics-serum OGX-427 trough levels [ Time Frame: During the trial and through the end of treatment visit (approx 6-8 months) ] [ Designated as safety issue: No ]
    To evaluate the effect of repeat OGX-427 dosing on serum OGX-427 trough levels summarized by treatment arm.


Estimated Enrollment: 180
Study Start Date: October 2011
Estimated Primary Completion Date: February 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: OGX-427 600 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (600 mg)
Drug: OGX-427 600 mg

Patients will receive three loading doses of 600 mg Study Drug within a 9-day period. Following the loading dose period, patients will receive weekly Study Drug infusions (600 mg IV) on Days 1, 8 and 15 of each 21-day cycle.

Patients will receive chemotherapy consisting of up to 6 cycles of gemcitabine and cisplatin.

Experimental: OGX-427 1000 mg
Standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 (1000 mg)
Drug: OGX-427 1000 mg

Patients will receive three loading doses of 600 mg Study Drug within a 9-day period. Following the loading dose period, patients will receive weekly Study Drug infusions (1000 mg IV) on Days 1, 8 and 15 of each 21-day cycle.

Patients will receive chemotherapy consisting of up to 6 cycles of gemcitabine and cisplatin.

Active Comparator: Placebo
Standard chemotherapy (gemcitabine and cisplatin) in combination with placebo
Drug: Placebo

Patients will receive three loading doses of placebo within a 9-day period. Following the loading dose period, patients will receive weekly placebo infusions (IV) on Days 1, 8 and 15 of each 21-day cycle.

Patients will receive chemotherapy consisting of up to 6 cycles of gemcitabine and cisplatin.


Detailed Description:

The incidence of bladder cancer in 2010 in the US and Canada combined is estimated to be 77,680, with 16,520 deaths and in Europe in 2008 was 110,500 with 38,200 deaths. The most common histological type is transitional cell cancer (TCC). Most cases (70%) present with superficial or non-invasive disease which, in general, has a good prognosis. However, at diagnosis, 20% of patients will have advanced disease (muscular invasion) and 5% will present with metastatic disease. In addition, 50-70% of superficial tumors will recur and a significant proportion will evolve to muscular involvement within 5 years. Radical cystectomy is the treatment of choice for patients with operable invasive disease. Patients who present with locally inoperable disease due to local extension into organs other than the bladder or involvement of regional lymph nodes do not have this option, and, despite radical cystectomy, 50% of patients will recur either regionally (~30%) or systemically (~70%) following cystectomy. Following recurrence, few patients can be cured.

Before the advent of chemotherapy, survival of patients with metastatic TCC was <6 months. Today, TCC is felt to be a chemotherapy sensitive disease, and systemic chemotherapy is the treatment of choice for patients with inoperable, locally advanced, or metastatic disease.

This study evaluates the safety and efficacy of the standard chemotherapy (gemcitabine and cisplatin) in combination with OGX-427 at two dose levels (600 mg and 1000 mg) or placebo in patients with advanced TCC who have not previously received chemotherapy for metastatic disease and are not candidates for potential curative surgery or radiotherapy.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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 chemotherapy may be allowed
  5. Minimum of 21 days since prior major surgery or radiation therapy
  6. Karnofsky performance status ≥70%
  7. Required laboratory values at baseline:

    • ANC ≥ 1.5x109 cells/L
    • platelet count ≥ 125 x 109/L
    • Calculated creatinine clearance ≥60 mL/minute
    • 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 contraceptives
  9. Willing to give written informed consent

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01454089

  Show 55 Study Locations
Sponsors and Collaborators
OncoGenex Technologies
OncoGenex Pharmaceuticals
PRA Health Sciences
Investigators
Principal Investigator: Daniel Petrylak, MD Columbia University
  More Information

No publications provided

Responsible Party: OncoGenex Technologies
ClinicalTrials.gov Identifier: NCT01454089     History of Changes
Other Study ID Numbers: OGX-427-02
Study First Received: October 5, 2011
Last Updated: August 5, 2014
Health Authority: United States: Food and Drug Administration
European Union: European Medicines Agency
Canada: Health Canada

Keywords provided by OncoGenex Technologies:
bladder
urinary tract
transitional cell carcinoma
metastatic bladder cancer
chemotherapy

Additional relevant MeSH terms:
Carcinoma, Transitional Cell
Neoplasms
Urinary Bladder Neoplasms
Urologic Neoplasms
Carcinoma
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Urinary Bladder Diseases
Urogenital Neoplasms
Urologic Diseases
Cisplatin
Gemcitabine
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on November 27, 2014