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

Indiana University30 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

NON_RANDOMIZED

Purpose

TREATMENT

Masking

NONE

Enrollment

Conditions

Estrogen Receptor-negative Breast Cancer Progesterone Receptor-negative Breast Cancer Recurrent Breast Cancer Stage IV Breast Cancer

Interventions

Medroxyprogesterone progesterone acetate (MPA)DRUG

1000 mg po daily

Medroxyprogesterone with Cyclophosphamide + MethotrexateDRUG

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

Eligibility

Sex: ALLMin age: 18 Years

Medical Language ↔ Plain English

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.

Locations (7)

University of Alabama at Birmingham

Birmingham, Alabama, United States

University of California, San Francisco Comprehensive Cancer Center

San Francisco, California, United States

Indiana University Melvin and Bren Simon Cancer Center

Indianapolis, Indiana, United States

Outcomes

Primary Outcomes

Clinical Benefit Rate (CR + PR + SD > 6 Months).

To determine the clinical benefit rate (Complete Response + Partial Response + Stable Disease \> 6 months) per Response Evaluation Criteria in Solid tumors (RECIST version 1.0). of MPA monotherapy and MPA + low dose oral cyclophosphamide and methotrexate (ldoCM) in patients with refractory hormone receptor negative metastatic breast cancer. This will show the percent of patients who had Clinical Benefit and the Exact 95% Confidence Interval.

Time frame: baseline through end of study, up to 3 years

Secondary Outcomes

Grade 3 or 4 Adverse Events Related to Treatment

To evaluate the toxicity of MPA and MPA + ldoCM in this patient population by the number of patients who have grade 3 or 4 adverse events that are related to treatment.

Time frame: baseline through end of treatment

MPA Trough Level > 50 ng/mL When Have Clinical Benefit

To explore the relationship between MPA trough level and clinical benefit. This is done by seeing if the MPA concentrations remained \> 50 ng/mL after initial dose escalation for those patients who showed clinical benefit. The number shows how many of the patients who showed clinical benefit had MPA concentrations \> 50 ng/mL.

Time frame: baseline through end of treatment

MPA Trough Concentration

To explore genetic determinants of MPA bioavailability and trough concentration by showing average MPA levels at cycle 1 (Day 10-14) and cycle 2 (Day 1).

Time frame: Cycle 1 (Day 10-14) and Cycle 2 (Day 1)

Data from ClinicalTrials.gov

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