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

October 12, 2023 updated by: Kathy Miller, Indiana University

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

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

30

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • University of Alabama at Birmingham
    • California
      • San Francisco, California, United States, 94115
        • University of California, San Francisco Comprehensive Cancer Center
    • Indiana
      • Indianapolis, Indiana, United States, 46202
        • Indiana University Melvin and Bren Simon Cancer Center
    • Massachusetts
      • Boston, Massachusetts, United States, 02115
        • Dana-Farber Cancer Institute
    • North Carolina
      • Chapel Hill, North Carolina, United States, 27599
        • University of North Carolina, Lineberger Comprehensive Cancer Center
      • Durham, North Carolina, United States, 27710
        • Duke University Comprehensive Cancer Center
    • Texas
      • Houston, Texas, United States, 77030
        • The University of Texas M. D. Anderson Cancer Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (Adult, Older Adult)

Accepts Healthy Volunteers

No

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Non-Randomized
  • Interventional Model: Parallel Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Cohort I (MPA)
Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.
Drug: Medroxyprogesterone progesterone acetate (MPA)
1000 mg po daily
Other Names:
  • Provera
  • Depo-Provera
  • Curretab
  • (6alpha)-17-hydroxy-6-methylpregn-4-ene-3,20-dione
  • 17alpha-hydroxy-6alpha-methylprogesterone
  • 27408
  • 520-85-4
  • 6alpha-methyl-17alpha-hydroxyprogesterone
  • 6alpha-methyl-4-pregnen-17alpha-ol-3,20-dione
  • Provera Dosepak
Experimental: Cohort II (MPA, low-dose chemotherapy)

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.
Drug: 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
Other Names:
  • CTX
  • methylaminopterin
  • MTX
  • MPA
  • medroxyprogesterone acetate
  • cyclophosphamid monohydrate

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Clinical Benefit Rate (CR + PR + SD > 6 Months).
Time Frame: baseline through end of study, up to 3 years
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 Outcome Measures

Outcome Measure
Measure Description
Time Frame
Grade 3 or 4 Adverse Events Related to Treatment
Time Frame: baseline through end of 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
MPA Trough Level > 50 ng/mL When Have Clinical Benefit
Time Frame: baseline through end of treatment
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
MPA Trough Concentration
Time Frame: Cycle 1 (Day 10-14) and Cycle 2 (Day 1)
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)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Indiana University

Collaborators

Translational Breast Cancer Research Consortium

Investigators

  • Principal Investigator: Kathy Miller, MD, IU Simon Cancer Center

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

July 1, 2007

Primary Completion (Actual)

December 1, 2011

Study Completion (Actual)

December 1, 2011

Study Registration Dates

First Submitted

December 18, 2007

First Submitted That Met QC Criteria

December 18, 2007

First Posted (Estimated)

December 19, 2007

Study Record Updates

Last Update Posted (Actual)

October 16, 2023

Last Update Submitted That Met QC Criteria

October 12, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 0607-18 IUCRO-0154
  • TBCRC 007 (Other Identifier: Translational Breast Cancer Reserach Consortium)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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