Clinical trial NCT00258375: OGX-011 and Docetaxel in Treating Women With Locally Advanced or Metastatic Breast Cancer
Official title: A Phase II Study of a Second Generation Clusterin Antisense Oligonucleotide (OGX-011) in Combination With Docetaxel in Advanced Breast Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Breast Cancer
Keywords: stage IIIA breast cancer
stage IIIB breast cancer
stage IIIC breast cancer
stage IV breast cancer
recurrent breast cancer
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2005-11-24
Enrollment: 15
Sex: FEMALE
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Objective response measured by RECIST criteria after accrual of 14 evaluable patients
Secondary outcomes:
measure: Toxicity
Other outcomes:
Locations:
city: Kelowna
country: Canada
facility: British Columbia Cancer Agency - Centre for the Southern Interior
state: British Columbia
city: Surrey
country: Canada
facility: BCCA - Fraser Valley Cancer Centre
state: British Columbia
city: Vancouver
country: Canada
facility: British Columbia Cancer Agency - Vancouver Cancer Centre
state: British Columbia
city: London
country: Canada
facility: London Regional Cancer Program at London Health Sciences Centre
state: Ontario
city: Ottawa
country: Canada
facility: Ottawa Hospital Regional Cancer Centre - General Campus
state: Ontario
Study officials:
affiliation: British Columbia Cancer Agency
name: Stephen Chia, MD
role: STUDY_CHAIR
References:
citation: 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.