Clinical trial NCT00577122: Medroxyprogesterone +/- Cyclophosphamide & Methotrexate in Hormone Receptor-Negative Recurrent/Metastatic Breast Cancer
Official title: MPA Revisited: A Phase II Study of Anti-Metastatic, Anti-Angiogenic Therapy in Postmenopausal Patients With Hormone Receptor Negative Breast Cancer. A Translational Breast Cancer Research Consortium (TBCRC) Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
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
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: Translational Breast Cancer Research Consortium
First posted: 2007-12-19
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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.

Primary outcomes:
measure: Clinical Benefit Rate (CR + PR + SD > 6 Months).
timeFrame: baseline through end of study, up to 3 years
Secondary outcomes:
measure: Grade 3 or 4 Adverse Events Related to Treatment
timeFrame: baseline through end of treatment
measure: MPA Trough Level > 50 ng/mL When Have Clinical Benefit
timeFrame: baseline through end of treatment
measure: MPA Trough Concentration
timeFrame: Cycle 1 (Day 10-14) and Cycle 2 (Day 1)
Other outcomes:
Locations:
city: Birmingham
country: United States
facility: University of Alabama at Birmingham
state: Alabama
city: San Francisco
country: United States
facility: University of California, San Francisco Comprehensive Cancer Center
state: California
city: Indianapolis
country: United States
facility: Indiana University Melvin and Bren Simon Cancer Center
state: Indiana
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Chapel Hill
country: United States
facility: University of North Carolina, Lineberger Comprehensive Cancer Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Comprehensive Cancer Center
state: North Carolina
city: Houston
country: United States
facility: The University of Texas M. D. Anderson Cancer Center
state: Texas
Study officials:
affiliation: IU Simon Cancer Center
name: Kathy Miller, MD
role: PRINCIPAL_INVESTIGATOR
References: