3-AP and Gemcitabine in Treating Patients With Refractory Metastatic Breast Cancer

National Cancer Institute (NCI)

Status and phase

Terminated

Phase 2

Conditions

Male Breast Cancer

Recurrent Breast Cancer

Stage IV Breast Cancer

Treatments

Drug: triapine

Other: laboratory biomarker analysis

Drug: gemcitabine hydrochloride

Other: pharmacological study

Study type

Interventional

Funder types

NIH

Identifiers

NCT00095888

NCI-2012-02632

N01CM62205 (U.S. NIH Grant/Contract)

MC0333

Details and patient eligibility

About

Phase II trial to study the effectiveness of combining 3-AP with gemcitabine in treating patients who have refractory metastatic breast cancer. Drugs used in chemotherapy, such as 3-AP and gemcitabine, work in different ways to stop tumor cells from dividing so they stop growing or die. Combining 3-AP with gemcitabine may kill more tumor cells

Full description

OBJECTIVES: Primary I. Determine antitumor activity of 3-AP (Triapine®) and gemcitabine by measuring tumor size in patients with refractory metastatic breast cancer.

Secondary I. Determine the safety and tolerability of this regimen in these patients. II. Determine the time to disease progression in patients treated with this regimen.

III. Determine the effect of multidrug resistance polymorphisms on pharmacokinetics and toxicity of this regimen in these patients.

OUTLINE: This is a multicenter study.

Patients receive 3-AP (Triapine®) IV over 2 hours followed by gemcitabine IV over 30 minutes on days 1, 8, and 15. Courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.

Patients are followed every 3 months until disease progression and then every 6 months for up to 3 years after registration.

PROJECTED ACCRUAL: A total of 30-75 patients will be accrued for this study within 24 months.

Enrollment

68 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically or cytologically confirmed breast cancer
- Refractory metastatic disease
Measurable disease
- At least 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques OR ≥ 10 mm by spiral CT scan
Must have received 1, and only 1, prior chemotherapy regimen for metastatic disease
Patients overexpressing HER2/neu antigen must have received a prior trastuzumab (Herceptin®)-containing regimen
No known brain metastases
Hormone receptor status:
- Not specified
Male or female
Performance status - ECOG 0-2
At least 12 weeks
WBC ≥ 3,000/mm^3
Absolute neutrophil count ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
Bilirubin normal
AST and ALT ≤ 2.5 times upper limit of normal
Creatinine normal
Creatinine clearance ≥ 60 mL/min
No uncontrolled congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No severe pulmonary disease requiring oxygen
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No glucose-6-phosphate dehydrogenase (G6PD) deficiency
No other uncontrolled illness
No active or ongoing infection
No history of allergic reaction attributed to compounds of similar chemical or biological composition to 3-AP (Triapine®) or other study agents
No psychiatric illness or social situation that would preclude study compliance
No other malignancy within the past 5 years
See Disease Characteristics
No concurrent immunotherapy
No concurrent routine colony-stimulating factors (e.g., filgrastim [G-CSF] or sargramostim [GM-CSF])
See Disease Characteristics
More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
No prior gemcitabine for metastatic disease
No other concurrent chemotherapy
More than 4 weeks since prior hormonal therapy
More than 4 weeks since prior radiotherapy
No concurrent radiotherapy
Recovered from prior therapy
No concurrent antiretroviral therapy for HIV-positive patients
No other concurrent investigational therapy