Conditions: Estrogen Receptor-negative Breast Cancer Progesterone Receptor-negative Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer
Keywords: Medroxyprogesterone progesterone acetate (MPA) Cyclophosphamide plus Methotrexate
Allocation: NON_RANDOMIZED | Intervention model: PARALLEL
Enrollment: 30
Healthy volunteers: no

Brief summary:
The purpose of this study is to evaluate the impact of MPA alone and in combination with low dose oral chemotherapy in patients with ER- and PR- advanced breast cancer.

Detailed description:
PRIMARY OBJECTIVES:

I. To determine the clinical benefit rate (complete response \[CR\] + partial response \[PR\] + stable disease \[SD\] \>= 6 months) of medroxyprogesterone acetate (MPA) monotherapy and MPA + low dose oral cyclophosphamide and methotrexate (ldoCM) in patients with refractory hormone receptor negative metastatic breast cancer.

SECONDARY OBJECTIVES:

I. To evaluate the toxicity of MPA and MPA + ldoCM in this patient population. II. To explore the relationship between MPA trough level and clinical benefit. III. To explore genetic determinants of MPA bioavailability and trough concentration.

IV. To explore potential surrogates of biologic activity including Nm-23 expression in primary tumor, change in Nm-23 expression in skin, change in plasma thrombospondin (TSP)-1, change in plasma plasminogen activator inhibitor (PAI)-1 antigen and activity.

OUTLINE: Patients are assigned to 1 of 2 treatment arms.

COHORT I: Patients receive MPA orally (PO) once daily (QD).

COHORT II: Patients receive MPA as in Cohort I, cyclophosphamide PO QD, and methotrexate PO twice daily (BID) on days 1 and 2 of every week.

In both arms, treatment continues in the absence of disease progression or unacceptable toxicity.

Arms:
arm 1: Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. arm 2: Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

Cyclophosphamide will be administered orally as a single daily dose. Methotrexate will be administered twice daily on days 1 and 2 of each week.

Interventions: intervention 1: Medroxyprogesterone progesterone acetate (MPA) intervention 2: Medroxyprogesterone with Cyclophosphamide + Methotrexate
Intervention descriptions: intervention 1: 1000 mg po daily intervention 2: Medroxyprogesterone Acetate Dose 1000 mg po daily Cyclophosphamide Dose 50 mg po daily Methotrexate Dose 2.5 mg po daily Days 1 and 2 of each week

Protocol document: