Estrogen Receptor-negative Breast CancerPhase 2NCT00577122
Medroxyprogesterone +/- Cyclophosphamide & Methotrexate in Hormone Receptor-Negative Recurrent/Metastatic Breast Cancer
A Phase 2 study testing Medroxyprogesterone progesterone acetate (MPA) and Medroxyprogesterone with Cyclophosphamide + Methotrexate in people with Estrogen Receptor-negative Breast Cancer and Progesterone Receptor-negative Breast Cancer, run by Indiana University at 7 sites in United States.
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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Estrogen Receptor-negative Breast Cancer, Progesterone Receptor-negative Breast Cancer, Recurrent Breast Cancer
- What is being tested?
- Medroxyprogesterone progesterone acetate (MPA) and Medroxyprogesterone with Cyclophosphamide + Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 7 sitesUnited States
- Study dates
- Jul 2007to Dec 2011
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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.
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
University of Alabama at Birmingham
Birmingham, Alabama, 35294
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
University of North Carolina, Lineberger Comprehensive Cancer Center
Chapel Hill, North Carolina, 27599
Duke University Comprehensive Cancer Center
Durham, North Carolina, 27710
The University of Texas M. D. Anderson Cancer Center
Houston, Texas, 77030
Indiana University Melvin and Bren Simon Cancer Center
Indianapolis, Indiana, 46202
University of California, San Francisco Comprehensive Cancer Center
San Francisco, California, 94115
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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:
- 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.
- Conditions
- Estrogen Receptor-negative Breast Cancer, Progesterone Receptor-negative Breast Cancer, Recurrent Breast Cancer, Stage IV Breast Cancer
- Being tested
- Medroxyprogesterone progesterone acetate (MPA), Medroxyprogesterone with Cyclophosphamide + Methotrexate
- Keywords
- Medroxyprogesterone progesterone acetate (MPA), Cyclophosphamide plus Methotrexate
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Medroxyprogesterone progesterone acetate (MPA)Drug
Also called (6alpha)-17-hydroxy-6-methylpregn-4-ene-3,20-dione, 17alpha-hydroxy-6alpha-methylprogesterone, 27408, 520-85-4
1000 mg po daily
Medroxyprogesterone with Cyclophosphamide + MethotrexateDrug
Also called medroxyprogesterone acetate, MPA, cyclophosphamid monohydrate, CTX
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
| Study group | Role | What they receive |
|---|---|---|
| Cohort I (MPA) | Experimental | Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. Receives: Drug: Medroxyprogesterone progesterone acetate (MPA) |
| Cohort II (MPA, low-dose chemotherapy) | Experimental | 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. Receives: Drug: Medroxyprogesterone with Cyclophosphamide + Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: baseline through end of study, up to 3 years
Secondary outcomes (3)
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.
Measured: baseline through end of treatment
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.
Measured: baseline through end of treatment
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).
Measured: Cycle 1 (Day 10-14) and Cycle 2 (Day 1)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Dec 2007 (estimated)
- Study startJul 2007
- Primary completionDec 2011
- Study completionDec 2011
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Estrogen Receptor-negative Breast CancerStudies of the same condition, open and under way.
- More trials run by Indiana UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- Indiana University
- Sponsor type
- University, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium
- Responsible party
- Principal investigator, Kathy Miller, Indiana University
- Investigators
- Kathy Miller, MD, Principal investigator, IU Simon Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00577122
- Sponsor's protocol ID
- 0607-18 IUCRO-0154
- Other IDs
- TBCRC 007
- Status last verified
- Oct 2023
- First submitted
- 18 Dec 2007
- Last updated
- 16 Oct 2023
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 16 Oct 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT00577122
- Acronym / sponsor ID
- 0607-18 IUCRO-0154
- 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
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- Indiana UniversityUniversity, hospital or other
- Collaborators
- Translational Breast Cancer Research Consortium
- Study start
- Jul 2007
- Primary completion
- Dec 2011 (actual)
- Study completion
- Dec 2011 (actual)
- First posted
- 19 Dec 2007 (estimated)
- Results
- Posted 23 Sep 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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:
- 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:
- 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 design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Cohort I (MPA) | Experimental | Drug: Medroxyprogesterone progesterone acetate (MPA)Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. |
| Cohort II (MPA, low-dose chemotherapy) | Experimental | Drug: Medroxyprogesterone with Cyclophosphamide + MethotrexateMedroxyprogesterone 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. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (4 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Medroxyprogesterone progesterone acetate (MPA)Also: (6alpha)-17-hydroxy-6-methylpregn-4-ene-3,20-dione, 17alpha-hydroxy-6alpha-methylprogesterone, 27408, 520-85-41000 mg po daily | Drug | Cohort I (MPA) |
| Medroxyprogesterone with Cyclophosphamide + MethotrexateAlso: medroxyprogesterone acetate, MPA, cyclophosphamid monohydrate, CTXMedroxyprogesterone 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 | Drug | Cohort II (MPA, low-dose chemotherapy) |
Primary outcome
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.
3 secondary outcomes
Grade 3 or 4 Adverse Events Related to Treatment
Time frame: baseline through end of treatment
MPA Trough Level > 50 ng/mL When Have Clinical Benefit
Time frame: baseline through end of treatment
MPA Trough Concentration
Time frame: Cycle 1 (Day 10-14) and Cycle 2 (Day 1)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 16 Oct 2023.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kathy Miller, MD principal investigator
IU Simon Cancer Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Medroxyprogesterone progesterone acetate (MPA) and Medroxyprogesterone with Cyclophosphamide + Methotrexate in people with Estrogen Receptor-negative Breast Cancer and Progesterone Receptor-negative Breast Cancer, run by Indiana University at 7 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 4 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 16 Oct 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 23 Sep 2014). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Clinical Benefit Rate (CR + PR + SD > 6 Months). (time frame: baseline through end of study, up to 3 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 16 Oct 2023.