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

Stage IV Breast Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00577122
• Other study ID #: 0607-18 IUCRO-0154
• Secondary ID: TBCRC 007
• Status: Completed
• Phase: Phase 2
• Start date: July 2007
• Est. completion date: December 2011

Study information

• Verified date: October 2023
• Source: Indiana University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 30
• Est. completion date: December 2011
• Est. primary completion date: December 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

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

Intervention

Drug:
• Medroxyprogesterone progesterone acetate (MPA)
1000 mg po daily
• Medroxyprogesterone with Cyclophosphamide + Methotrexate
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

Locations

Country	Name	City	State
United States	University of Alabama at Birmingham	Birmingham	Alabama
United States	Dana-Farber Cancer Institute	Boston	Massachusetts
United States	University of North Carolina, Lineberger Comprehensive Cancer Center	Chapel Hill	North Carolina
United States	Duke University Comprehensive Cancer Center	Durham	North Carolina
United States	The University of Texas M. D. Anderson Cancer Center	Houston	Texas
United States	Indiana University Melvin and Bren Simon Cancer Center	Indianapolis	Indiana
United States	University of California, San Francisco Comprehensive Cancer Center	San Francisco	California

Sponsors (2)

Lead Sponsor	Collaborator
Indiana University	Translational Breast Cancer Research Consortium

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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.	baseline through end of study, up to 3 years
Secondary	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.	baseline through end of treatment
Secondary	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.	baseline through end of treatment
Secondary	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).	Cycle 1 (Day 10-14) and Cycle 2 (Day 1)