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

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ClinicalTrials.gov Identifier: NCT00577122
Recruitment Status : Completed
First Posted : December 19, 2007
Results First Posted : September 23, 2014
Last Update Posted : October 3, 2014
Sponsor:
Collaborator:
Translational Breast Cancer Research Consortium
Information provided by (Responsible Party):
Indiana University

Study Type Interventional
Study Design Allocation: Non-Randomized;   Intervention Model: Parallel Assignment;   Masking: None (Open Label);   Primary Purpose: Treatment
Conditions Estrogen Receptor-negative Breast Cancer
Progesterone Receptor-negative Breast Cancer
Recurrent Breast Cancer
Stage IV Breast Cancer
Interventions Drug: Medroxyprogesterone progesterone acetate (MPA)
Drug: Medroxyprogesterone with Cyclophosphamide + Methotrexate
Enrollment 30
Recruitment Details 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.
Pre-assignment Details  
Arm/Group Title Cohort 1: MPA-Alone Cohort 2: MPA+IdoCM
Hide Arm/Group Description Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

Period Title: Overall Study
Started 14 16
Completed 0 0
Not Completed 14 16
Reason Not Completed
Adverse Event             0             2
Progression, relapse during active trt             6             8
Prog, refract disease during active trt             8             5
Alternative Therapy             0             1
Arm/Group Title Cohort 1: MPA-Alone Cohort 2: MPA+IdoCM Total
Hide Arm/Group Description Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

Total of all reporting groups
Overall Number of Baseline Participants 14 16 30
Hide Baseline Analysis Population Description
[Not Specified]
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
9
  64.3%
12
  75.0%
21
  70.0%
>=65 years
5
  35.7%
4
  25.0%
9
  30.0%
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 14 participants 16 participants 30 participants
59.0  (12.78) 56.2  (12.24) 57.5  (12.36)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
Female
14
 100.0%
16
 100.0%
30
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Ethnicity (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
Hispanic or Latino
0
   0.0%
0
   0.0%
0
   0.0%
Not Hispanic or Latino
14
 100.0%
16
 100.0%
30
 100.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 14 participants 16 participants 30 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
1
   6.3%
1
   3.3%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
5
  35.7%
3
  18.8%
8
  26.7%
White
9
  64.3%
12
  75.0%
21
  70.0%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
1.Primary Outcome
Title Clinical Benefit Rate (CR + PR + SD > 6 Months).
Hide Description 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.
Time Frame baseline through end of study, up to 3 years
Hide Outcome Measure Data
Hide Analysis Population Description
All Patients on study.
Arm/Group Title Cohort I: MPA-Alone Cohort 2: MPA+IdoCM
Hide Arm/Group Description:
Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

Overall Number of Participants Analyzed 14 16
Measure Type: Number
Number (95% Confidence Interval)
Unit of Measure: Percent of Participants
7.1
(0.2 to 33.9)
6.3
(0.2 to 30.2)
2.Secondary Outcome
Title Grade 3 or 4 Adverse Events Related to Treatment
Hide Description 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.
Time Frame baseline through end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
All patients in the study
Arm/Group Title Cohort I: MPA-Alone Cohort II: MPA+IdoCM
Hide Arm/Group Description:
Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

Overall Number of Participants Analyzed 14 16
Measure Type: Number
Unit of Measure: participants
2 2
3.Secondary Outcome
Title MPA Trough Level > 50 ng/mL When Have Clinical Benefit
Hide Description 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.
Time Frame baseline through end of treatment
Hide Outcome Measure Data
Hide Analysis Population Description
Patients who showed clinical benefit (CR, PR, or SD > 6 months)
Arm/Group Title Cohort I: MPA-Alone Cohort II: MPA+IdoCM
Hide Arm/Group Description:
Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

Overall Number of Participants Analyzed 1 1
Measure Type: Number
Unit of Measure: participants
1 1
4.Secondary Outcome
Title MPA Trough Concentration
Hide Description 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).
Time Frame Cycle 1 (Day 10-14) and Cycle 2 (Day 1)
Hide Outcome Measure Data
Hide Analysis Population Description
All patients with available data
Arm/Group Title Cohort I: MPA-Alone Cohort II: MPA+IdoCM
Hide Arm/Group Description:
Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

Overall Number of Participants Analyzed 14 16
Mean (Standard Deviation)
Unit of Measure: ng/mL
Cycle 1, Day 10-14 14.5  (8.9) 42.1  (66.4)
Cycle 2, Day 1 52.6  (65.3) 66.4  (71.5)
Time Frame Throughout the entire study, up to 3 years.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Cohort 1: MPA Alone Cohort 2: MPA+IdoCM
Hide Arm/Group Description Medroxyprogesterone progesterone acetate (MPA) will be administered orally as a single daily dose.

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.

All-Cause Mortality
Cohort 1: MPA Alone Cohort 2: MPA+IdoCM
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Cohort 1: MPA Alone Cohort 2: MPA+IdoCM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   2/14 (14.29%)      2/16 (12.50%)    
Metabolism and nutrition disorders     
DEHYDRATION *  0/14 (0.00%)  0 1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders     
FRACTURE *  1/14 (7.14%)  1 0/16 (0.00%)  0
Renal and urinary disorders     
RENAL FAILURE *  0/14 (0.00%)  0 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders     
DYSPNEA (SHORTNESS OF BREATH) *  0/14 (0.00%)  0 2/16 (12.50%)  2
ASPIRATION *  0/14 (0.00%)  0 1/16 (6.25%)  1
HYPOXIA *  0/14 (0.00%)  0 1/16 (6.25%)  1
PNEUMOTHORAX *  1/14 (7.14%)  1 0/16 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 5%
Cohort 1: MPA Alone Cohort 2: MPA+IdoCM
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   14/14 (100.00%)      12/16 (75.00%)    
Blood and lymphatic system disorders     
DERMAL CHANGE LYMPHEDEMA, PHLEBOLYMPHEDEMA *  1/14 (7.14%)  1 0/16 (0.00%)  0
LYMPHATICS *  0/14 (0.00%)  0 1/16 (6.25%)  1
Ear and labyrinth disorders     
AUDITORY/EAR *  1/14 (7.14%)  1 0/16 (0.00%)  0
Gastrointestinal disorders     
CONSTIPATION *  5/14 (35.71%)  5 4/16 (25.00%)  4
DIARRHEA *  1/14 (7.14%)  1 2/16 (12.50%)  2
DRY MOUTH/SALIVARY GLAND (XEROSTOMIA) *  1/14 (7.14%)  1 0/16 (0.00%)  0
DYSPHAGIA (DIFFICULTY SWALLOWING) *  0/14 (0.00%)  0 1/16 (6.25%)  1
GASTRITIS (INCLUDING BILE REFLUX GASTRITIS) *  1/14 (7.14%)  1 1/16 (6.25%)  1
GASTROINTESTINAL - OTHER (SPECIFY, __) *  0/14 (0.00%)  0 2/16 (12.50%)  2
HEARTBURN/DYSPEPSIA *  1/14 (7.14%)  1 1/16 (6.25%)  1
MUCOSITIS/STOMATITIS (CLINICAL EXAM) - STOMACH *  0/14 (0.00%)  0 1/16 (6.25%)  1
MUCOSITIS/STOMATITIS (FUNCTIONAL/SYMPTOMATIC) - ESOPHAGUS *  0/14 (0.00%)  0 1/16 (6.25%)  1
NAUSEA *  3/14 (21.43%)  3 3/16 (18.75%)  3
PAIN - ABDOMEN NOS *  0/14 (0.00%)  0 2/16 (12.50%)  2
TASTE ALTERATION (DYSGEUSIA) *  3/14 (21.43%)  3 1/16 (6.25%)  1
VOMITING *  2/14 (14.29%)  2 0/16 (0.00%)  0
General disorders     
FATIGUE (ASTHENIA, LETHARGY, MALAISE) *  7/14 (50.00%)  7 7/16 (43.75%)  7
FEVER (IN THE ABSENCE OF NEUTROPENIA, WHERE NEUTROPENIA IS DEFINED AS ANC <1.0 X 10E9/L) *  0/14 (0.00%)  0 2/16 (12.50%)  2
PAIN - OTHER (SPECIFY, __) *  3/14 (21.43%)  3 3/16 (18.75%)  3
Infections and infestations     
INFECTION - OTHER (SPECIFY, __) *  0/14 (0.00%)  0 1/16 (6.25%)  1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - BLADDER (URINARY) *  0/14 (0.00%)  0 1/16 (6.25%)  1
INFECTION WITH NORMAL ANC OR GRADE 1 OR 2 NEUTROPHILS - LUNG (PNEUMONIA) *  0/14 (0.00%)  0 1/16 (6.25%)  1
INFECTION WITH UNKNOWN ANC - NECK NOS *  1/14 (7.14%)  1 0/16 (0.00%)  0
PAIN - SKIN *  0/14 (0.00%)  0 1/16 (6.25%)  1
Injury, poisoning and procedural complications     
BURN *  0/14 (0.00%)  0 1/16 (6.25%)  1
Investigations     
ALKALINE PHOSPHATASE *  0/14 (0.00%)  0 1/16 (6.25%)  1
ALT, SGPT (SERUM GLUTAMIC PYRUVIC TRANSAMINASE) *  0/14 (0.00%)  0 1/16 (6.25%)  1
AST, SGOT(SERUM GLUTAMIC OXALOACETIC TRANSAMINASE) *  1/14 (7.14%)  1 0/16 (0.00%)  0
BICARBONATE, SERUM-LOW *  1/14 (7.14%)  1 0/16 (0.00%)  0
HEMOGLOBIN *  2/14 (14.29%)  2 0/16 (0.00%)  0
INR (INTERNATIONAL NORMALIZED RATIO OF PROTHROMBIN TIME) *  2/14 (14.29%)  2 0/16 (0.00%)  0
METABOLIC/LABORATORY - OTHER (SPECIFY, __) *  0/14 (0.00%)  0 1/16 (6.25%)  1
PTT (PARTIAL THROMBOPLASTIN TIME) *  1/14 (7.14%)  1 0/16 (0.00%)  0
WEIGHT GAIN *  0/14 (0.00%)  0 1/16 (6.25%)  1
Metabolism and nutrition disorders     
ANOREXIA *  1/14 (7.14%)  1 1/16 (6.25%)  1
CALCIUM, SERUM-LOW (HYPOCALCEMIA) *  1/14 (7.14%)  1 0/16 (0.00%)  0
POTASSIUM, SERUM-LOW (HYPOKALEMIA) *  1/14 (7.14%)  1 0/16 (0.00%)  0
URIC ACID, SERUM-HIGH (HYPERURICEMIA) *  0/14 (0.00%)  0 1/16 (6.25%)  1
Musculoskeletal and connective tissue disorders     
EDEMA: LIMB *  3/14 (21.43%)  3 1/16 (6.25%)  1
PAIN - BACK *  2/14 (14.29%)  2 3/16 (18.75%)  3
PAIN - BONE *  0/14 (0.00%)  0 2/16 (12.50%)  2
PAIN - CHEST WALL *  0/14 (0.00%)  0 2/16 (12.50%)  2
PAIN - CHEST/THORAX NOS *  2/14 (14.29%)  2 0/16 (0.00%)  0
PAIN - EXTREMITY-LIMB *  2/14 (14.29%)  2 1/16 (6.25%)  1
PAIN - JOINT *  1/14 (7.14%)  1 2/16 (12.50%)  2
PAIN - MUSCLE *  1/14 (7.14%)  1 1/16 (6.25%)  1
PAIN - NECK *  1/14 (7.14%)  1 0/16 (0.00%)  0
PAIN - PAIN NOS *  1/14 (7.14%)  1 0/16 (0.00%)  0
Nervous system disorders     
ENCEPHALOPATHY *  1/14 (7.14%)  1 0/16 (0.00%)  0
NEUROLOGY - OTHER (SPECIFY, __) *  0/14 (0.00%)  0 1/16 (6.25%)  1
NEUROPATHY: SENSORY *  6/14 (42.86%)  6 2/16 (12.50%)  2
PAIN - HEAD/HEADACHE *  1/14 (7.14%)  1 2/16 (12.50%)  2
PAIN - NEURALGIA/PERIPHERAL NERVE *  0/14 (0.00%)  0 1/16 (6.25%)  1
SPEECH IMPAIRMENT (E.G., DYSPHASIA OR APHASIA) *  1/14 (7.14%)  1 0/16 (0.00%)  0
SWEATING (DIAPHORESIS) *  2/14 (14.29%)  2 0/16 (0.00%)  0
TREMOR *  1/14 (7.14%)  1 0/16 (0.00%)  0
Psychiatric disorders     
INSOMNIA *  5/14 (35.71%)  5 5/16 (31.25%)  5
MOOD ALTERATION - AGITATION *  0/14 (0.00%)  0 1/16 (6.25%)  1
MOOD ALTERATION - ANXIETY *  4/14 (28.57%)  4 2/16 (12.50%)  2
MOOD ALTERATION - DEPRESSION *  4/14 (28.57%)  4 2/16 (12.50%)  2
Reproductive system and breast disorders     
HOT FLASHES/FLUSHES *  4/14 (28.57%)  4 2/16 (12.50%)  2
IRREGULAR MENSES (CHANGE FROM BASELINE) *  0/14 (0.00%)  0 1/16 (6.25%)  1
MEMORY IMPAIRMENT *  1/14 (7.14%)  1 1/16 (6.25%)  1
PAIN - BREAST *  2/14 (14.29%)  2 1/16 (6.25%)  1
VAGINAL DRYNESS *  0/14 (0.00%)  0 1/16 (6.25%)  1
Respiratory, thoracic and mediastinal disorders     
ALLERGIC RHINITIS (INCLUDING SNEEZING, NASAL STUFFINESS, POSTNASAL DRIP) *  0/14 (0.00%)  0 1/16 (6.25%)  1
COUGH *  7/14 (50.00%)  7 5/16 (31.25%)  5
DIZZINESS *  1/14 (7.14%)  1 0/16 (0.00%)  0
DYSPNEA (SHORTNESS OF BREATH) *  8/14 (57.14%)  8 7/16 (43.75%)  7
HICCOUGHS (HICCUPS, SINGULTUS) *  0/14 (0.00%)  0 1/16 (6.25%)  1
NASAL CAVITY/PARANASAL SINUS REACTIONS *  1/14 (7.14%)  1 0/16 (0.00%)  0
VOICE CHANGES/DYSARTHRIA (E.G., HOARSENESS, LOSS OR ALTERATION IN VOICE, LARYNGITIS) *  1/14 (7.14%)  1 2/16 (12.50%)  2
Skin and subcutaneous tissue disorders     
ATROPHY, SKIN *  1/14 (7.14%)  1 0/16 (0.00%)  0
DERMATOLOGY/SKIN - OTHER (SPECIFY, __) *  2/14 (14.29%)  2 1/16 (6.25%)  1
HAIR LOSS/ALOPECIA (SCALP OR BODY) *  3/14 (21.43%)  3 1/16 (6.25%)  1
MUCOSITIS/STOMATITIS (CLINICAL EXAM) - ORAL CAVITY *  1/14 (7.14%)  1 3/16 (18.75%)  3
NAIL CHANGES *  1/14 (7.14%)  1 0/16 (0.00%)  0
PRURITUS/ITCHING *  1/14 (7.14%)  1 1/16 (6.25%)  1
RASH/DESQUAMATION *  2/14 (14.29%)  2 3/16 (18.75%)  3
ULCERATION *  1/14 (7.14%)  1 0/16 (0.00%)  0
*
Indicates events were collected by non-systematic assessment
Certain Agreements
All Principal Investigators ARE employed by the organization sponsoring the study.
Results Point of Contact
Name/Title: Kathy Miller, MD
Organization: IndianaU
Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00577122     History of Changes
Other Study ID Numbers: 0607-18 IUCRO-0154
TBCRC 007 ( Other Identifier: Translational Breast Cancer Reserach Consortium )
First Submitted: December 18, 2007
First Posted: December 19, 2007
Results First Submitted: September 16, 2014
Results First Posted: September 23, 2014
Last Update Posted: October 3, 2014