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

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

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.

Study Overview

• Status: Completed
• Conditions: Kidney Cancer; Breast Cancer; Ovarian Cancer; Lung Cancer; Prostate Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Bladder Cancer
• Intervention / Treatment: Other: pharmacological study; Drug: docetaxel; Drug: custirsen sodium

Detailed 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.

• Study Type: Interventional
• Enrollment (Actual): 40
• Phase: Phase 1

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 120 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Dose-limiting toxicity
Recommended phase II dose of OGX-011

Secondary Outcome Measures

Outcome Measure
Objective response
Pharmacokinetic profile
Serum clusterin levels and clusterin expression in peripheral blood mononuclear cells and accessible tumors

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Kim N. Chi, MD, British Columbia Cancer Agency

Publications and helpful links

General Publications

• Chi KN, Siu LL, Hirte H, Hotte SJ, Knox J, Kollmansberger C, Gleave M, Guns E, Powers J, Walsh W, Tu D, Eisenhauer E. A phase I study of OGX-011, a 2'-methoxyethyl phosphorothioate antisense to clusterin, in combination with docetaxel in patients with advanced cancer. Clin Cancer Res. 2008 Feb 1;14(3):833-9. doi: 10.1158/1078-0432.CCR-07-1310.

Study record dates

Study Major Dates

• Study Start (Actual): April 4, 2003
• Primary Completion (Actual): March 9, 2006
• Study Completion (Actual): December 21, 2009

Study Registration Dates

• First Submitted: May 8, 2007
• First Submitted That Met QC Criteria: May 8, 2007
• First Posted (Estimated): May 10, 2007

Study Record Updates

• Last Update Posted (Actual): August 4, 2023
• Last Update Submitted That Met QC Criteria: August 3, 2023
• Last Verified: April 1, 2020

More Information

Terms related to this study

• Keywords: stage IV renal cell cancer; recurrent renal cell cancer; stage IV breast cancer; recurrent breast cancer; recurrent non-small cell lung cancer; recurrent bladder cancer; stage IV bladder cancer; stage IV prostate cancer; recurrent prostate cancer; stage IV non-small cell lung cancer; unspecified adult solid tumor, protocol specific; stage IV ovarian epithelial cancer; recurrent ovarian epithelial cancer; male breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Respiratory Tract Diseases; Neoplasms; Lung Diseases; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Kidney Diseases; Urologic Diseases; Urinary Bladder Diseases; Genital Neoplasms, Male; Breast Diseases; Prostatic Diseases; Respiratory Tract Neoplasms; Thoracic Neoplasms; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Genital Diseases, Male; Genital Diseases; Kidney Neoplasms; Breast Neoplasms; Prostatic Neoplasms; Lung Neoplasms; Urinary Bladder Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: I154; CAN-NCIC-IND154 (Other Identifier: PDQ); ONCOGENEX-OGX-01-02 (Other Identifier: Oncogenex Technologies); CDR0000547039 (Other Identifier: PDQ)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No