OGX-011 and Docetaxel in Treating Women With Locally Advanced or Metastatic Breast Cancer

A Phase II Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel in Advanced Breast Cancer

RATIONALE: 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. OGX-011 may help docetaxel kill more tumor cells by making tumor cells more sensitive to the drug.

PURPOSE: This phase II trial is studying how well giving OGX-011 together with docetaxel works in treating women with locally advanced or metastatic breast cancer.

Study Overview

• Status: Completed
• Conditions: Breast Cancer
• Intervention / Treatment: Drug: docetaxel; Drug: custirsen sodium

Detailed Description

OBJECTIVES:

Primary

• Determine the efficacy of OGX-011 and docetaxel, in terms of objective tumor response rate, in women with locally advanced or metastatic breast cancer.

Secondary

• Determine the tolerability and toxicity of this regimen in these patients.
• Determine the time to progression and overall survival of patients treated with this regimen.

OUTLINE: This is an open-label, nonrandomized, multicenter study.

Patients receive OGX-011 IV over 2 hours on days -7, -5, -3, 1, 8, and 15 of course 1 and on days 1, 8, and 15 of all subsequent courses. Patients also receive docetaxel IV over 1 hour on days 1 and 8 of all courses. Treatment repeats every 21 days* for up to 10 courses in the absence of disease progression or unacceptable toxicity.

NOTE: *Course 1 is 28 days in length and all subsequent courses (courses 2-10) are 21 days in length.

After completion of study treatment, patients are followed at 4 weeks and then periodically until disease progression.

PROJECTED ACCRUAL: Approximately 42 patients will be accrued for this study.

• Study Type: Interventional
• Enrollment (Actual): 15
• Phase: Phase 2

Contacts and Locations

Study Locations

• Canada
  • British Columbia
    • Kelowna, British Columbia, Canada, V1Y 5L3
      • British Columbia Cancer Agency - Centre for the Southern Interior
    • Surrey, British Columbia, Canada, V3V 1Z2
      • BCCA - Fraser Valley Cancer Centre
    • Vancouver, British Columbia, Canada, V5Z 4E6
      • British Columbia Cancer Agency - Vancouver Cancer Centre
  • Ontario
    • London, Ontario, Canada, N6A 4L6
      • London Regional Cancer Program at London Health Sciences Centre
    • Ottawa, Ontario, Canada, K1H 8L6
      • Ottawa Hospital Regional Cancer Centre - General Campus

Participation Criteria

Eligibility Criteria

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

Description

DISEASE CHARACTERISTICS:

• Histologically confirmed breast cancer

  • Metastatic or locally advanced disease
  • Not curable with standard therapy

• Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan

  • Lesion must be outside of the previously irradiated field

    • If the sole site of disease is in a previously irradiated field, there must be evidence of disease progression or new lesions in the irradiated field
• No known CNS metastases

• Hormone receptor status:

  • Not specified

PATIENT CHARACTERISTICS:

Sex

• Female

Menopausal status

• Not specified

Performance status

• ECOG 0-2

Life expectancy

• At least 12 weeks

Hematopoietic

• Platelet count ≥ 100,000/mm^3
• Absolute granulocyte count ≥ 1,500/mm^3
• PTT, PT, and INR normal
• No known bleeding disorder

Hepatic

• Bilirubin normal
• AST and ALT ≤ 1.5 times upper limit of normal (ULN)

Renal

• Creatinine ≤ 1.5 times ULN

Cardiovascular

• No significant cardiac dysfunction

Immunologic

• No active uncontrolled infection
• No history of serious allergic reaction to taxanes, including paclitaxel or docetaxel

Other

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No preexisting neuropathy ≥ grade 2
• No other malignancies within the past 5 years except adequately treated nonmelanoma skin cancer or curatively treated carcinoma in situ of the cervix
• No other serious medical condition or illness that would preclude study participation
• No significant neurological disorder that would preclude giving informed consent

PRIOR CONCURRENT THERAPY:

Biologic therapy

• Prior trastuzumab (Herceptin^®) allowed

Chemotherapy

• Recovered from prior chemotherapy
• At least 6 months since prior adjuvant chemotherapy (taxanes allowed)

• At least 4 weeks since prior chemotherapy for advanced disease

  • No prior taxanes for advanced disease
• No more than 1 prior chemotherapy regimen for advanced disease
• No other concurrent chemotherapy

Endocrine therapy

• At least 1 week since prior hormonal therapy

Radiotherapy

• See Disease Characteristics

• At least 4 weeks since prior radiotherapy

  • Low-dose, nonmyelosuppressive radiotherapy allowed within 4 weeks before study entry at the discretion of the investigator
• No prior radiotherapy ≥ 30% of functioning bone marrow
• No concurrent radiotherapy

Surgery

• At least 3 weeks since prior major surgery and recovered (wound healing must have occurred)

Other

• More than 4 weeks since prior investigational agents or new anticancer therapy
• No concurrent therapeutic anticoagulation therapy except low-dose oral anticoagulant therapy (i.e., 1 mg of oral warfarin once a day) or low molecular weight heparin
• No other concurrent investigational therapy
• No other concurrent cytotoxic therapy

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
Objective response measured by RECIST criteria after accrual of 14 evaluable patients

Secondary Outcome Measures

Outcome Measure
Toxicity

Collaborators and Investigators

• Sponsor: NCIC Clinical Trials Group
• Investigators: Study Chair: Stephen Chia, MD, British Columbia Cancer Agency

Publications and helpful links

General Publications

• Chia S, Dent S, Ellard SL, et al.: A phase II trial of a second generation antisense oligonucleotide (ASO) to clusterin (OGX-011) in combination with docetaxel in metastatic breast cancer (MBC): NCIC-CTG IND 164 trial. [Abstract] American Association for Cancer Research: 98th Annual Meeting, April 14-18, 2007, Los Angeles, CA. A-3512, 2007.

Study record dates

Study Major Dates

• Study Start (Actual): October 21, 2005
• Primary Completion (Actual): February 23, 2007
• Study Completion (Actual): September 22, 2008

Study Registration Dates

• First Submitted: November 22, 2005
• First Submitted That Met QC Criteria: November 22, 2005
• First Posted (Estimated): November 24, 2005

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 breast cancer; stage IIIA breast cancer; recurrent breast cancer; stage IIIB breast cancer; stage IIIC breast cancer
• Additional Relevant MeSH Terms: Skin Diseases; Neoplasms; Neoplasms by Site; Breast Diseases; Breast Neoplasms; Molecular Mechanisms of Pharmacological Action; Antineoplastic Agents; Tubulin Modulators; Antimitotic Agents; Mitosis Modulators; Docetaxel
• Other Study ID Numbers: I164; CAN-NCIC-IND164 (Other Identifier: PDQ); ONCOGENEX-OGX-011-06 (Other Identifier: Oncogenex Technologies); CDR0000450847 (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