A Phase 2 Study Comparing Chemotherapy in Combination With OGX-427 or Placebo in Patients With Bladder Cancer
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Purpose
| 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 |
- 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.
- 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.
| Enrollment: | 182 |
| Study Start Date: | October 2011 |
| Study Completion Date: | November 2014 |
| Primary Completion Date: | November 2014 (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 (Adult, Senior) |
| Genders Eligible for Study: | Both |
| Accepts Healthy Volunteers: | No |
Inclusion Criteria:
- Age ≥ 18 years at the time of consent
- 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.
- 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
-
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
- Minimum of 21 days since prior major surgery or radiation therapy
- Karnofsky performance status ≥70%
-
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
- If of child-bearing potential, willing to use contraceptives
- Willing to give written informed consent
Exclusion Criteria:
- A candidate for potential curative surgery or radiotherapy
- Intravesical therapy within the last 3 months
- 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.
- Peripheral neuropathy ≥Grade 2
- Known serious hypersensitivity to gemcitabine, cisplatin or carboplatin
- 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
- 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
- Pregnant or nursing (must have a negative serum or urine pregnancy test within 72 hours prior to randomization)
- Participating in a concurrent clinical trial of an experimental drug, vaccine or device. Participation in an observational study is allowed.
Contacts and LocationsPlease refer to this study by its ClinicalTrials.gov identifier: NCT01454089
Show 55 Study Locations
| Principal Investigator: | Daniel Petrylak, MD | Columbia University |
More Information
| 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: | October 22, 2015 |
| 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:
|
Neoplasms Urinary Bladder Neoplasms Carcinoma, Transitional Cell Urologic Neoplasms Urogenital Neoplasms Neoplasms by Site Urinary Bladder Diseases Urologic Diseases Carcinoma Neoplasms, Glandular and Epithelial Neoplasms by Histologic Type Gemcitabine |
Cisplatin Antineoplastic Agents Antimetabolites, Antineoplastic Antimetabolites Molecular Mechanisms of Pharmacological Action Antiviral Agents Anti-Infective Agents Enzyme Inhibitors Immunosuppressive Agents Immunologic Factors Physiological Effects of Drugs |
ClinicalTrials.gov processed this record on September 23, 2016