Medroxyprogesterone +/- Cyclophosphamide & Methotrexate in Hormone Receptor-Negative Recurrent/Metastatic Breast Cancer

Indiana University

Status and phase: Completed; Phase 2

Conditions: Progesterone Receptor-negative Breast Cancer; Estrogen Receptor-negative Breast Cancer; Recurrent Breast Cancer; Stage IV Breast Cancer

Treatments: Drug: Medroxyprogesterone progesterone acetate (MPA); Drug: Medroxyprogesterone with Cyclophosphamide + Methotrexate

Study type: Interventional

Funder types: Other

Identifiers

NCT00577122

0607-18 IUCRO-0154

TBCRC 007 (Other Identifier)

Details and patient eligibility

About

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.

Full 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.

Enrollment: 30 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Histologically or cytologically confirmed adenocarcinoma of the breast with measurable locally recurrent or metastatic disease
• Primary tumor must be ER negative and PR negative
• Patients must be post-menopausal
• Patients may have had up to 3 prior chemotherapy regimens for recurrent/metastatic disease
• Adequate organ function as evidenced by laboratory studies outlined in section 3.6 of the protocol
• Patients with treated, asymptomatic brain metastases are eligible provided chronic steroid therapy is not required

Exclusion criteria

• Patients must not have extensive pleural effusion or ascites
• Patients must not have history of DVT or pulmonary embolism w/in past 12 mo
• Patients must not have had chemotherapy or hormonal therapy within 2 weeks of study entry
• Patients must not have had radiation therapy within 1 week of study entry.

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Parallel Assignment

Masking: None (Open label)

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30 participants in 2 patient groups

Cohort I (MPA)

Experimental group

Description:

Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

Treatment:

Drug: Medroxyprogesterone progesterone acetate (MPA)

Cohort II (MPA, low-dose chemotherapy)

Experimental group

Description:

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.

Treatment:

Drug: Medroxyprogesterone with Cyclophosphamide + Methotrexate