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| ID | Type | Description | Link |
|---|---|---|---|
| TBCRC 007 | Other Identifier | Translational Breast Cancer Reserach Consortium |
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| Name | Class |
|---|---|
| Translational Breast Cancer Research Consortium | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Cohort I (MPA) | Experimental | Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. |
|
| 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. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Medroxyprogesterone progesterone acetate (MPA) | Drug | 1000 mg po daily |
|
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| MPA Trough Level > 50 ng/mL When Have Clinical Benefit |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Kathy Miller, MD | IU Simon Cancer Center | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Alabama at Birmingham | Birmingham | Alabama | 35294 | United States | ||
| University of California, San Francisco Comprehensive Cancer Center |
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Since there was not enough evidence of clinical benefit, this study did not go beyond the first stage in the two stage design. A total of 30 patients (14 in the MPA alone cohort and 16 in the MPA+ ldoCM cohort) were in the study before the study ended.
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| ID | Title | Description |
|---|---|---|
| FG000 | Cohort 1: MPA-Alone | Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. |
| FG001 | Cohort 2: MPA+IdoCM | 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. |
| Title | Milestones | Reasons Not Completed | |||||
|---|---|---|---|---|---|---|---|
| Overall Study |
|
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| Medroxyprogesterone with Cyclophosphamide + Methotrexate | Drug | 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 |
|
|
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 | 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) |
| San Francisco |
| California |
| 94115 |
| United States |
| Indiana University Melvin and Bren Simon Cancer Center | Indianapolis | Indiana | 46202 | United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02115 | United States |
| University of North Carolina, Lineberger Comprehensive Cancer Center | Chapel Hill | North Carolina | 27599 | United States |
| Duke University Comprehensive Cancer Center | Durham | North Carolina | 27710 | United States |
| The University of Texas M. D. Anderson Cancer Center | Houston | Texas | 77030 | United States |
| COMPLETED |
|
| NOT COMPLETED |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Cohort 1: MPA-Alone | Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. |
| BG001 | Cohort 2: MPA+IdoCM | 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. |
| BG002 | Total | Total of all reporting groups |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants | Participants |
| ||||||||||||||||||
| Age, Continuous | Mean | Standard Deviation | Years |
| |||||||||||||||||
| Sex: Female, Male | Count of Participants | Participants |
| ||||||||||||||||||
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
| ||||||||||||||||||
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 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. | All Patients on study. | Posted | Number | 95% Confidence Interval | Percent of Participants | 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. | All patients in the study | Posted | Number | participants | 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. | Patients who showed clinical benefit (CR, PR, or SD > 6 months) | Posted | Number | participants | 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). | All patients with available data | Posted | Mean | Standard Deviation | ng/mL | Cycle 1 (Day 10-14) and Cycle 2 (Day 1) |
|
|
Throughout the entire study, up to 3 years.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Cohort 1: MPA Alone | Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose. | 2 | 14 | 14 | 14 | ||
| EG001 | Cohort 2: MPA+IdoCM | 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. | 2 | 16 | 12 | 16 |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| DYSPNEA (SHORTNESS OF BREATH) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| DEHYDRATION | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| FRACTURE | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| RENAL FAILURE | Renal and urinary disorders | Non-systematic Assessment |
| ||
| ASPIRATION | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| HYPOXIA | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| PNEUMOTHORAX | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
|
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| DERMAL CHANGE LYMPHEDEMA, PHLEBOLYMPHEDEMA | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| LYMPHATICS | Blood and lymphatic system disorders | Non-systematic Assessment |
| ||
| AUDITORY/EAR | Ear and labyrinth disorders | Non-systematic Assessment |
| ||
| CONSTIPATION | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| DIARRHEA | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| DRY MOUTH/SALIVARY GLAND (XEROSTOMIA) | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| DYSPHAGIA (DIFFICULTY SWALLOWING) | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| GASTRITIS (INCLUDING BILE REFLUX GASTRITIS) | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| GASTROINTESTINAL - OTHER (SPECIFY, __) | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| HEARTBURN/DYSPEPSIA | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| MUCOSITIS/STOMATITIS (CLINICAL EXAM) - STOMACH | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| MUCOSITIS/STOMATITIS (FUNCTIONAL/SYMPTOMATIC) - ESOPHAGUS | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| NAUSEA | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| PAIN - ABDOMEN NOS | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| TASTE ALTERATION (DYSGEUSIA) | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| VOMITING | Gastrointestinal disorders | Non-systematic Assessment |
| ||
| FATIGUE (ASTHENIA, LETHARGY, MALAISE) | General disorders | Non-systematic Assessment |
| ||
| FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L) | General disorders | Non-systematic Assessment |
| ||
| PAIN - OTHER (SPECIFY, __) | General disorders | Non-systematic Assessment |
| ||
| INFECTION - OTHER (SPECIFY, __) | Infections and infestations | Non-systematic Assessment |
| ||
| INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - BLADDER (URINARY) | Infections and infestations | Non-systematic Assessment |
| ||
| INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - LUNG (PNEUMONIA) | Infections and infestations | Non-systematic Assessment |
| ||
| INFECTION WITH UNKNOWN ANC - NECK NOS | Infections and infestations | Non-systematic Assessment |
| ||
| PAIN - SKIN | Infections and infestations | Non-systematic Assessment |
| ||
| BURN | Injury, poisoning and procedural complications | Non-systematic Assessment |
| ||
| ALKALINE PHOSPHATASE | Investigations | Non-systematic Assessment |
| ||
| ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE) | Investigations | Non-systematic Assessment |
| ||
| AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE) | Investigations | Non-systematic Assessment |
| ||
| BICARBONATE, SERUM-LOW | Investigations | Non-systematic Assessment |
| ||
| HEMOGLOBIN | Investigations | Non-systematic Assessment |
| ||
| INR (INTERNATIONAL NORMALIZED RATIO OF PROTHROMBIN TIME) | Investigations | Non-systematic Assessment |
| ||
| METABOLIC/LABORATORY - OTHER (SPECIFY, __) | Investigations | Non-systematic Assessment |
| ||
| PTT (PARTIAL THROMBOPLASTIN TIME) | Investigations | Non-systematic Assessment |
| ||
| WEIGHT GAIN | Investigations | Non-systematic Assessment |
| ||
| ANOREXIA | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| CALCIUM, SERUM-LOW (HYPOCALCEMIA) | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| POTASSIUM, SERUM-LOW (HYPOKALEMIA) | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| URIC ACID, SERUM-HIGH (HYPERURICEMIA) | Metabolism and nutrition disorders | Non-systematic Assessment |
| ||
| EDEMA: LIMB | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - BACK | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - BONE | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - CHEST WALL | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - CHEST/THORAX NOS | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - EXTREMITY-LIMB | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - JOINT | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - MUSCLE | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - NECK | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| PAIN - PAIN NOS | Musculoskeletal and connective tissue disorders | Non-systematic Assessment |
| ||
| ENCEPHALOPATHY | Nervous system disorders | Non-systematic Assessment |
| ||
| NEUROLOGY - OTHER (SPECIFY, __) | Nervous system disorders | Non-systematic Assessment |
| ||
| NEUROPATHY: SENSORY | Nervous system disorders | Non-systematic Assessment |
| ||
| PAIN - HEAD/HEADACHE | Nervous system disorders | Non-systematic Assessment |
| ||
| PAIN - NEURALGIA/PERIPHERAL NERVE | Nervous system disorders | Non-systematic Assessment |
| ||
| SPEECH IMPAIRMENT (E.G., DYSPHASIA OR APHASIA) | Nervous system disorders | Non-systematic Assessment |
| ||
| SWEATING (DIAPHORESIS) | Nervous system disorders | Non-systematic Assessment |
| ||
| TREMOR | Nervous system disorders | Non-systematic Assessment |
| ||
| INSOMNIA | Psychiatric disorders | Non-systematic Assessment |
| ||
| MOOD ALTERATION - AGITATION | Psychiatric disorders | Non-systematic Assessment |
| ||
| MOOD ALTERATION - ANXIETY | Psychiatric disorders | Non-systematic Assessment |
| ||
| MOOD ALTERATION - DEPRESSION | Psychiatric disorders | Non-systematic Assessment |
| ||
| HOT FLASHES/FLUSHES | Reproductive system and breast disorders | Non-systematic Assessment |
| ||
| IRREGULAR MENSES (CHANGE FROM BASELINE) | Reproductive system and breast disorders | Non-systematic Assessment |
| ||
| MEMORY IMPAIRMENT | Reproductive system and breast disorders | Non-systematic Assessment |
| ||
| PAIN - BREAST | Reproductive system and breast disorders | Non-systematic Assessment |
| ||
| VAGINAL DRYNESS | Reproductive system and breast disorders | Non-systematic Assessment |
| ||
| ALLERGIC RHINITIS (INCLUDING SNEEZING, NASAL STUFFINESS, POSTNASAL DRIP) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| COUGH | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| DIZZINESS | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| DYSPNEA (SHORTNESS OF BREATH) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| HICCOUGHS (HICCUPS, SINGULTUS) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| NASAL CAVITY/PARANASAL SINUS REACTIONS | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| VOICE CHANGES/DYSARTHRIA (E.G., HOARSENESS, LOSS OR ALTERATION IN VOICE, LARYNGITIS) | Respiratory, thoracic and mediastinal disorders | Non-systematic Assessment |
| ||
| ATROPHY, SKIN | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| DERMATOLOGY/SKIN - OTHER (SPECIFY, __) | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| HAIR LOSS/ALOPECIA (SCALP OR BODY) | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| MUCOSITIS/STOMATITIS (CLINICAL EXAM) - ORAL CAVITY | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| NAIL CHANGES | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| PRURITUS/ITCHING | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| RASH/DESQUAMATION | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
| ||
| ULCERATION | Skin and subcutaneous tissue disorders | Non-systematic Assessment |
|
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Kathy Miller, MD | IndianaU | kathmill@iupui.edu |
| ID | Term |
|---|---|
| D001943 | Breast Neoplasms |
| ID | Term |
|---|---|
| D009371 | Neoplasms by Site |
| D009369 | Neoplasms |
| D001941 | Breast Diseases |
| D012871 | Skin Diseases |
| D017437 | Skin and Connective Tissue Diseases |
Not provided
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| ID | Term |
|---|---|
| D008525 | Medroxyprogesterone |
| D017258 | Medroxyprogesterone Acetate |
| D003520 | Cyclophosphamide |
| D008727 | Methotrexate |
| ID | Term |
|---|---|
| D006908 | Hydroxyprogesterones |
| D011374 | Progesterone |
| D011282 | Pregnenediones |
| D011283 | Pregnenes |
| D011278 | Pregnanes |
| D013256 | Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |
| D010752 | Phosphoramide Mustards |
| D009588 | Nitrogen Mustard Compounds |
| D009150 | Mustard Compounds |
| D006846 | Hydrocarbons, Halogenated |
| D006838 | Hydrocarbons |
| D009930 | Organic Chemicals |
| D063088 | Phosphoramides |
| D009943 | Organophosphorus Compounds |
| D000630 | Aminopterin |
| D011622 | Pterins |
| D011621 | Pteridines |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| D006571 | Heterocyclic Compounds |
Not provided
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| >=65 years |
|
| Male |
|
| Not Hispanic or Latino |
|
| Unknown or Not Reported |
|
| Asian |
|
| Native Hawaiian or Other Pacific Islander |
|
| Black or African American |
|
| White |
|
| More than one race |
|
| Unknown or Not Reported |
|
|
|
|