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

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Translational Breast Cancer Reserach Consortium
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00577122
First received: December 18, 2007
Last updated: August 7, 2013
Last verified: March 2013
  Purpose

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.


Condition Intervention Phase
Estrogen Receptor-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Drug: Medroxyprogesterone progesterone acetate (MPA)
Drug: Medroxyprogesterone with Cyclophosphamide + Methotrexate
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • To determine the clinical benefit rate (CR + PR + SD > 6 months) of MPA monotherapy and MPA + low dose oral cyclophosphamide and methotrexate (ldoCM) in patients with refractory hormone receptor negative metastatic breast cancer. [ Time Frame: baseline through end of study ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To evaluate the toxicity of MPA and MPA + ldoCM in this patient population [ Time Frame: baseline through end of treatment ] [ Designated as safety issue: Yes ]
  • To explore the relationship between MPA trough level and clinical benefit [ Time Frame: baseline through end of treatment ] [ Designated as safety issue: No ]
  • To explore genetic determinants of MPA bioavailability and trough concentration [ Time Frame: baseline through end of treatment ] [ Designated as safety issue: No ]
  • To explore potential surrogates of biologic activity including Nm-23 expression in primary tumor, change in Nm-23 expression in skin, change in plasma TSP-1, change in plasma PAI-1 antigen and activity. [ Time Frame: baseline through end of treatment ] [ Designated as safety issue: No ]

Enrollment: 31
Study Start Date: July 2007
Estimated Study Completion Date: December 2013
Primary Completion Date: December 2011 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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:
  • (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
  • Curretab
  • Depo-Provera
  • Provera
  • 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:
  • medroxyprogesterone acetate
  • MPA
  • cyclophosphamid monohydrate
  • CTX
  • methylaminopterin
  • MTX

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Please refer to this study by its ClinicalTrials.gov identifier: NCT00577122

Locations
United States, Alabama
University of Alabama at Birmingham
Birmingham, Alabama, United States, 35294
United States, California
University of California, San Francisco Comprehensive Cancer Center
San Francisco, California, United States, 94115
United States, Indiana
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, United States, 46202
United States, Massachusetts
Dana-Farber Cancer Institute
Boston, Massachusetts, United States, 02115
United States, North Carolina
University of North Carolina, Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, United States, 27599
Duke University Comprehensive Cancer Center
Durham, North Carolina, United States, 27710
United States, Texas
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, United States, 77030
Sponsors and Collaborators
Indiana University
Translational Breast Cancer Reserach Consortium
Investigators
Principal Investigator: Kathy Miller, MD IU Simon Cancer Center
  More Information

No publications provided

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00577122     History of Changes
Other Study ID Numbers: 0607-18 IUCRO-0154, TBCRC 007
Study First Received: December 18, 2007
Last Updated: August 7, 2013
Health Authority: United States: Institutional Review Board

Keywords provided by Indiana University:
Medroxyprogesterone progesterone acetate (MPA)
Cyclophosphamide plus Methotrexate

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Cyclophosphamide
Methotrexate
Medroxyprogesterone Acetate
17-alpha-hydroxy-progesterone caproate
11-hydroxyprogesterone
Progesterone
Medroxyprogesterone
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Antirheumatic Agents
Therapeutic Uses
Antineoplastic Agents, Alkylating
Alkylating Agents
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Myeloablative Agonists
Progestins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Estradiol Antagonists
Estrogen Antagonists
Estrogen Receptor Modulators
Hormone Antagonists

ClinicalTrials.gov processed this record on April 17, 2014