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

NCIC Clinical Trials Group

Status and phase

Completed

Phase 1

Conditions

Breast Cancer

Bladder Cancer

Unspecified Adult Solid Tumor, Protocol Specific

Lung Cancer

Kidney Cancer

Ovarian Cancer

Prostate Cancer

Treatments

Drug: docetaxel

Other: pharmacological study

Drug: custirsen sodium

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00471432

I154

CDR0000547039 (Other Identifier)

CAN-NCIC-IND154 (Other Identifier)

ONCOGENEX-OGX-01-02 (Other Identifier)

Details and patient eligibility

About

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.

Full description

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.

Enrollment

40 patients

Sex

All

Ages

18 to 120 years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

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)