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

This study has been completed.
Sponsor:
Collaborator:
Translational Breast Cancer Research Consortium
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00577122
First received: December 18, 2007
Last updated: September 24, 2014
Last verified: September 2014

December 18, 2007
September 24, 2014
July 2007
December 2011   (final data collection date for primary outcome measure)
Clinical Benefit Rate (CR + PR + SD > 6 Months). [ Time Frame: baseline through end of study, up to 3 years ] [ Designated as safety issue: No ]
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.
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 ]
Complete list of historical versions of study NCT00577122 on ClinicalTrials.gov Archive Site
  • Grade 3 or 4 Adverse Events Related to Treatment [ Time Frame: baseline through end of treatment ] [ Designated as safety issue: Yes ]
    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.
  • MPA Trough Level > 50 ng/mL When Have Clinical Benefit [ Time Frame: baseline through end of treatment ] [ Designated as safety issue: No ]
    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.
  • MPA Trough Concentration [ Time Frame: Cycle 1 (Day 10-14) and Cycle 2 (Day 1) ] [ Designated as safety issue: No ]
    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).
  • 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 ]
Not Provided
Not Provided
 
Medroxyprogesterone +/- Cyclophosphamide & Methotrexate in Hormone Receptor-Negative Recurrent/Metastatic Breast Cancer
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.

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.

Interventional
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Estrogen Receptor-negative Breast Cancer
  • Progesterone Receptor-negative Breast Cancer
  • Recurrent Breast Cancer
  • Stage IV Breast Cancer
  • 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
  • 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
  • Experimental: Cohort I (MPA)
    Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.
    Intervention: Drug: Medroxyprogesterone progesterone acetate (MPA)
  • 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.

    Intervention: Drug: Medroxyprogesterone with Cyclophosphamide + Methotrexate
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
30
December 2011
December 2011   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT00577122
0607-18 IUCRO-0154, TBCRC 007
Yes
Indiana University
Indiana University
Translational Breast Cancer Research Consortium
Principal Investigator: Kathy Miller, MD IU Simon Cancer Center
Indiana University
September 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP