Alternate Title
Basic Trial Information
Objectives
Entry Criteria
Expected Enrollment
Outline
Trial Contact Information

Alternate Title

Trastuzumab Plus CpG 7909 in Treating Women With Metastatic Breast Cancer That Has Not Responded to Previous Trastuzumab and Chemotherapy

Basic Trial Information

Phase	Type	Status	Age	Sponsor	Protocol IDs
Phase II, Phase I	Treatment	Completed	18 and over	Pharmaceutical / Industry	CPGI-C005 CPGI-C005-CPG7909, CPGI-WIRB-20011156, NCI-V02-1697

Objectives

1. Determine the maximum tolerated dose of CpG 7909 in combination with trastuzumab (Herceptin) in women with metastatic breast cancer refractory to trastuzumab and chemotherapy.
2. Determine the safety and tolerability of this regimen in these patients.
3. Determine the tumor response and duration of response in patients treated with this regimen.
4. Determine the time to progression and overall survival of patients treated with this regimen.

Entry Criteria

Disease Characteristics:

• Histologically confirmed breast cancer
  • Metastatic disease



• HER2 overexpression as documented by being either FISH-positive or HER2/neu 3+ confirmed by immunohistochemistry



• Must have received at least 1, but no more than 2, prior chemotherapy regimens for metastatic breast cancer
  • Most recent regimen must have been in combination with trastuzumab (Herceptin)
  • No prior anthracycline with trastuzumab



• Disease progression documented during prior trastuzumab and chemotherapy after more than 4 weeks of therapy
  • No more than 42 days since last dose of failed treatment



• At least 1 unidimensionally measurable lesion
  • At least 20 mm by conventional techniques

    OR

  • At least 10 mm by spiral CT scan



• No known CNS metastases that are uncontrolled or treated within the past 2 months



• Hormone receptor status:
  • Not specified

Prior/Concurrent Therapy:

Biologic therapy:

• See Disease Characteristics

Chemotherapy:

• See Disease Characteristics
• Prior adjuvant chemotherapy allowed

Endocrine therapy:

• At least 1 week since prior systemic corticosteroids

Radiotherapy:

• Not specified

Surgery:

• No prior transplantation

Other:

• At least 30 days since prior participation in an investigational drug study
• Recovered from adverse events of agents administered more than 30 days ago
• No concurrent anticoagulants except salicylates, heparin flush, or low-dose warfarin to maintain line patency

Patient Characteristics:

Age:

• 18 and over

Sex:

• Female

Menopausal status:

• Not specified

Performance status:

• ECOG 0-2

Life expectancy:

• More than 3 months

Hematopoietic:

• Neutrophil count at least 1,500/mm3
• Platelet count at least 100,000/mm3

Hepatic:

• Bilirubin less than 2 mg/dL
• Transaminase less than 2 times upper limit of normal
• No concurrent significant hepatic disease

Renal:

• Creatinine less than 2 mg/dL
• No concurrent significant renal disease

Cardiovascular:

• No significant cardiovascular disease
• No New York Heart Association class III congestive heart failure
• No myocardial infarction within the past 6 months
• No unstable angina
• No coronary angioplasty within the past 6 months
• No uncontrolled atrial or ventricular arrhythmias
• LVEF at least 50%

Pulmonary:

• No concurrent significant pulmonary disease

Immunologic:

• No pre-existing autoimmune or antibody-mediated diseases
• No systemic lupus erythematosus
• No rheumatoid arthritis
• No multiple sclerosis
• No Sjogren's syndrome
• No autoimmune thrombocytopenia
• No history of allergic reactions to compounds of similar composition to CpG 7909 and/or trastuzumab except a mild hypersensitivity reaction associated with the first infusion of trastuzumab

Other:

• Not pregnant or nursing
• Negative pregnancy test
• Fertile patients must use effective contraception
• No acute infection or fever over 38.2 degrees Celsius within the past 3 days
• No suspected or confirmed poor compliance or mental instabilities that would preclude study
• No other medical history, including lab results, that would preclude study

Expected Enrollment

A total of 12-64 patients (12-24 for phase I and 15-40 for phase II) will be accrued for this study.

Outline

This is a multicenter, dose-escalation study of CpG 7909.

• Phase I: Patients receive trastuzumab (Herceptin) IV over 30-90 minutes followed by CpG 7909 IV over 2 hours once weekly for 8-24 weeks in the absence of disease progression or unacceptable toxicity.

  Cohorts of 3-6 patients receive escalating doses of CpG 7909 until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.




• Phase II: Once the MTD is determined, additional patients receive trastuzumab and CpG 7909 at the MTD as above.

Patients are followed within 2 weeks and then every 3 months thereafter.

Trial Contact Information

Trial Lead Organizations

Coley Pharmaceutical Group, Incorporated

Cheryl Eaton, Protocol chair(Contact information may not be current)		Ph: 781-431-9000