OGX-011 and Docetaxel in Treating Patients With Metastatic or Locally Recurrent Solid Tumors

Study Overview
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Brief Summary
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RATIONALE: OGX-011 may kill tumor cells by blocking some of the proteins that may cause tumor cells to grow. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving OGX-011 together with docetaxel may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of OGX-011 when given together with docetaxel in treating patients with metastatic or locally recurrent solid tumors.

Detailed Description
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OBJECTIVES: Primary Determine the dose-limiting toxicity and recommended phase II dose of OGX-011 when administered with docetaxel in patients with metastatic or locally recurrent solid tumors. Secondary Determine the pharmacokinetic profile of this regimen in these patients. Assess the effect of OGX-011 on serum clusterin levels and clusterin expression in peripheral blood mononuclear cells and accessible tumors. Assess objective response in patients treated with this regimen. OUTLINE: This is an open-label, multicenter, dose-escalation study of OGX-011. Patients are sequentially assigned to 1 of 2 treatment schedules. Schedule A: Patients receive OGX-011 IV over 2 hours on days 1, 3, 5, 8, 15, 22, 29, and 36 of course 1 and once weekly in weeks 1-6 of all subsequent courses. Patients also receive docetaxel IV over 1 hour once weekly in weeks 1-5. Treatment repeats every 6 weeks for up to 4 courses in the absence of disease progression or unacceptable toxicity. Schedule B: Patients receive OGX-011 IV over 2 hours on days -7, -5, -3, 1, 8, and 15 of course 1 and days 1, 8, and 15 of all subsequent courses. Patients also receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks (course 1 is 4 weeks in duration) for up to 4 courses in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of OGX-011 (in each schedule) until the recommended phase II dose (RPTD) is determined. The RPTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity. Patients undergo serum collection periodically for pharmacokinetic and pharmacodynamic analysis. After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter. PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.

Official Title
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A Phase I Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel

Conditions
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Bladder Cancer, Breast Cancer, Kidney Cancer, Lung Cancer, Ovarian Cancer, Prostate Cancer, Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
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* Drug: custirsen sodium
* Drug: docetaxel
* Other: pharmacological study


Participation Criteria
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Eligibility Criteria
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DISEASE CHARACTERISTICS: Histologically or cytologically confirmed solid tumors that have been shown to overexpress clusterin, including but not limited to, any of the following: Prostate cancer Renal cell carcinoma Non-small cell lung cancer Bladder cancer Breast cancer Ovarian cancer Metastatic or locally recurrent disease Refractory to standard curative therapy or no standard curative therapy exists Patients with prostate cancer must be hormone refractory (i.e., have documented evidence of progression while receiving androgen ablative therapy) Measurable or nonmeasurable disease Measurable disease defined as measurable lesion ≥ 20 mm by x-ray, physical exam, or nonspiral CT scan or ≥ 10 mm by spiral CT scan No documented CNS metastases Hormone receptor status not specified PATIENT CHARACTERISTICS: Menopausal status not specified ECOG performance status 0-2 Life expectancy ≥ 12 weeks Absolute granulocyte count ≥ 1,500/mm³ Platelet count ≥ 100,000/mm³ Bilirubin normal Creatinine ≤ 2 times upper limit of normal (ULN) AST and ALT ≤ 1.5 times ULN PT/INR and PTT normal No uncontrolled pain No known bleeding disorder No history of serious allergic reaction to taxane (paclitaxel or docetaxel) No preexisting peripheral neuropathy ≥ grade 2 Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception No other serious illness or medical conditions that would preclude study compliance, including any of the following: Active uncontrolled infection Significant cardiac dysfunction No significant neurological disorder that would preclude giving informed consent PRIOR CONCURRENT THERAPY: No prior strontium chloride Sr 89 No more than 2 prior chemotherapy regimens, including adjuvant or neoadjuvant chemotherapy (for patients assigned to schedule B [docetaxel once every 3 weeks]) More than 4 weeks since prior chemotherapy and recovered At least 4 weeks since prior antiandrogens More than 4 weeks since prior external-beam radiotherapy, except low-dose nonmyelosuppressive radiotherapy No prior radiotherapy to ≥ 30% of marrow-bearing areas (for patients assigned to schedule B [docetaxel once every 3 weeks]) At least 28 days since prior new anticancer therapy At least 28 days since prior and no other concurrent investigational agents No concurrent radiotherapy, except low-dose nonmyelosuppressive radiotherapy No other concurrent cytotoxic therapy Concurrent luteinizing hormone-releasing hormone agonist allowed (if already initiated in patients with prostate cancer) No concurrent anticoagulant therapy (i.e., heparin, warfarin)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: custirsen sodium|nan|
|Drug: docetaxel|nan|
|Other: pharmacological study|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dose-limiting toxicity |  |  | 
| Recommended phase II dose of OGX-011 |  |  | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pharmacokinetic profile |  |  | 
| Serum clusterin levels and clusterin expression in peripheral blood mononuclear cells and accessible tumors |  |  | 
| Objective response |  |  | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stage IV non-small cell lung cancer, recurrent prostate cancer, stage IV prostate cancer, recurrent renal cell cancer, stage IV renal cell cancer, recurrent non-small cell lung cancer, recurrent bladder cancer, stage IV bladder cancer, recurrent breast cancer, stage IV breast cancer, recurrent ovarian epithelial cancer, stage IV ovarian epithelial cancer, unspecified adult solid tumor, protocol specific, male breast cancer