Use of Metformin to Reduce Cardiac Toxicity in Breast Cancer

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ClinicalTrials.gov Identifier: NCT02472353

Recruitment Status : Terminated (did not meet target accrual)

First Posted : June 15, 2015

Results First Posted : October 16, 2019

Last Update Posted : October 16, 2019

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Sponsor:

Information provided by (Responsible Party):

Avera McKennan Hospital & University Health Center

Study Type	Interventional
Study Design	Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Prevention
Conditions	Breast Cancer Breast Tumors
Interventions	Drug: Metformin Drug: Doxorubicin
Enrollment	30

Participant Flow

Recruitment Details	Referrals and investigator's own patients
Pre-assignment Details


Arm/Group Title	Standard of Care	Metformin + Standard of Care
Arm/Group Description	Patients will receive standard of c...	Patients will receive metformin dur...
Arm/Group Description	Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. Doxorubicin: Standard of care treatment with doxorubicin	Patients will receive metformin during their treatment with doxorubicin for their breast cancer. Metformin: Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy. Doxorubicin: Standard of care treatment with doxorubicin
Period Title: Overall Study
Started	14	16
Completed	10	10
Not Completed	4	6
Reason Not Completed
Lost to Follow-up	1	1
Withdrawal by Subject	2	1
Study Termination	1	4

Baseline Characteristics

Arm/Group Title		Standard of Care	Metformin + Standard of Care	Total
Arm/Group Description		Patients will receive standard of c...	Patients will receive metformin dur...	Total of all reporting groups
Arm/Group Description		Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. Doxorubicin: Standard of care treatment with doxorubicin	Patients will receive metformin during their treatment with doxorubicin for their breast cancer. Metformin: Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy. Doxorubicin: Standard of care treatment with doxorubicin	Total of all reporting groups
Overall Number of Baseline Participants		14	16	30
Baseline Analysis Population Description		[Not Specified]
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	14 100.0%	12 75.0%	26 86.7%
	>=65 years	0 0.0%	4 25.0%	4 13.3%
Age, Continuous Mean (Full Range) Unit of measure: Years
	Number Analyzed	14 participants	16 participants	30 participants
		43 (31 to 64)	53 (29 to 68)	53 (29 to 68)
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%	1 6.3%	1 3.3%
	Not Hispanic or Latino	14 100.0%	15 93.8%	29 96.7%
	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%	0 0.0%	0 0.0%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	0 0.0%	0 0.0%	0 0.0%
	White	14 100.0%	16 100.0%	30 100.0%
	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%
Region of Enrollment Measure Type: Count of Participants Unit of measure: Participants
United States	Number Analyzed	14 participants	16 participants	30 participants
United States		14 100.0%	16 100.0%	30 100.0%
Echocardiography Measure Type: Number Unit of measure: Participants
	Number Analyzed	14 participants	16 participants	30 participants
		14	16	30

Outcome Measures

1.Primary Outcome


Title	Number of Participants With Less Than or Equal to 5% Decrease in Left Ventricle Ejection Fraction (LVEF) on Echocardiogram
Description	Determine whether the addition of metformin to standard doxorubicin th...
Description	Determine whether the addition of metformin to standard doxorubicin therapy in breast cancer patients will decrease the incidence of change in left ventricle ejection fraction (LVEF).
Time Frame	1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]


Arm/Group Title	Standard of Care	Metformin + Standard of Care
Arm/Group Description:	Patients will receive standard of c...	Patients will receive metformin dur...
Arm/Group Description:	Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. Doxorubicin: Standard of care treatment with doxorubicin	Patients will receive metformin during their treatment with doxorubicin for their breast cancer. Metformin: Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy. Doxorubicin: Standard of care treatment with doxorubicin
Overall Number of Participants Analyzed	10	10
Measure Type: Count of Participants Unit of Measure: Participants
	4 40.0%	5 50.0%

Adverse Events

Time Frame	Time point 1: Within 2 weeks of starting metformin Time point 2: 4 weeks after starting metformin Time point 3: 7 weeks after starting metformin Time point 4: 9 weeks after starting metformin (last assessment during treatment period)
Adverse Event Reporting Description	[Not Specified]

Arm/Group Title	Standard of Care		Metformin + Standard of Care
Arm/Group Description	Patients will receive standard of c...		Patients will receive metformin dur...
Arm/Group Description	Patients will receive standard of care for their breast cancer with no metformin during their treatment with doxorubicin. Doxorubicin: Standard of care treatment with doxorubicin		Patients will receive metformin during their treatment with doxorubicin for their breast cancer. Metformin: Metformin will begin to be administered prior to treatment with doxorubicin. Metformin will continue to be given throughout doxorubicin cycles until the completion of doxorubicin therapy. Doxorubicin: Standard of care treatment with doxorubicin
All-Cause Mortality
	Standard of Care		Metformin + Standard of Care
	Affected / at Risk (%)		Affected / at Risk (%)
Total	0/14 (0.00%)		0/16 (0.00%)
Serious Adverse Events Serious Adverse Events
	Standard of Care		Metformin + Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/14 (0.00%)		3/16 (18.75%)
Blood and lymphatic system disorders
Febrile neutropenia ^† 1	0/14 (0.00%)	0	2/16 (12.50%)	3
General disorders
Pain ^* 1 [1]	0/14 (0.00%)	0	1/16 (6.25%)	1
Infections and infestations
Infection ^† 1 [2]	0/14 (0.00%)	0	1/16 (6.25%)	1
1 Term from vocabulary, MedDRA 10.0 † Indicates events were collected by systematic assessment * Indicates events were collected by non-systematic assessment [1] admitted for pain control for herpes zoster outbreak [2] admitted for central line infection
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Standard of Care		Metformin + Standard of Care
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	12/14 (85.71%)		16/16 (100.00%)
Blood and lymphatic system disorders
Anemia ^† 1	10/14 (71.43%)	17	14/16 (87.50%)	39
Febrile Neutropenia ^† 1	3/14 (21.43%)	4	2/16 (12.50%)	2
Cardiac disorders
Tachycardia ^† 1	1/14 (7.14%)	1	4/16 (25.00%)	6
Eye disorders
Water Eyes ^† 1	1/14 (7.14%)	1	2/16 (12.50%)	2
Gastrointestinal disorders
Diarrhea ^† 1	8/14 (57.14%)	12	13/16 (81.25%)	26
Constipation ^† 1	7/14 (50.00%)	12	7/16 (43.75%)	13
Nausea ^† 1	9/14 (64.29%)	16	12/16 (75.00%)	29
Oral Mucositis ^† 1	7/14 (50.00%)	7	7/16 (43.75%)	10
Vomiting ^† 1	3/14 (21.43%)	4	5/16 (31.25%)	6
Dyspnea ^† 1	5/14 (35.71%)	6	2/16 (12.50%)	6
General disorders
Pain ^† 1	9/14 (64.29%)	15	6/16 (37.50%)	7
Fatigue ^† 1	12/14 (85.71%)	20	16/16 (100.00%)	49
Fever ^† 1	1/14 (7.14%)	1	2/16 (12.50%)	2
Edema ^* 1	1/14 (7.14%)	1	5/16 (31.25%)	7
Infections and infestations
Sepsis ^† 1	0/14 (0.00%)	0	2/16 (12.50%)	2
Investigations
Decreased Platelets ^* 1	2/14 (14.29%)	2	2/16 (12.50%)	2
Decreased WBC ^* 1	4/14 (28.57%)	4	6/16 (37.50%)	9
Weight Loss ^† 1	2/14 (14.29%)	2	4/16 (25.00%)	6
Increased AST ^† 1	1/14 (7.14%)	1	2/16 (12.50%)	2
Increased ALT ^† 1	4/14 (28.57%)	4	3/16 (18.75%)	3
Metabolism and nutrition disorders
Anorexia ^† 1	4/14 (28.57%)	5	11/16 (68.75%)	22
Musculoskeletal and connective tissue disorders
Myalgia ^† 1	6/14 (42.86%)	8	3/16 (18.75%)	4
Arthralgia ^† 1	4/14 (28.57%)	7	5/16 (31.25%)	8
Nervous system disorders
Headache ^† 1	6/14 (42.86%)	10	9/16 (56.25%)	19
Dysphagia ^† 1	0/14 (0.00%)	0	2/16 (12.50%)	2
Dizziness ^† 1	1/14 (7.14%)	1	3/16 (18.75%)	3
Neuropathy ^† 1	7/14 (50.00%)	9	4/16 (25.00%)	7
Dysgeusia ^† 1	9/14 (64.29%)	11	7/16 (43.75%)	12
Psychiatric disorders
Depression ^† 1	3/14 (21.43%)	4	3/16 (18.75%)	4
Anxiety ^† 1	6/14 (42.86%)	6	9/16 (56.25%)	15
Insomnia ^† 1	9/14 (64.29%)	12	10/16 (62.50%)	28
Respiratory, thoracic and mediastinal disorders
Sore Throat ^† 1	5/14 (35.71%)	6	3/16 (18.75%)	3
Allergic Rhinitis ^† 1	0/14 (0.00%)	0	3/16 (18.75%)	3
Cough ^† 1	8/14 (57.14%)	12	7/16 (43.75%)	12
Skin and subcutaneous tissue disorders
Alopecia ^† 1	8/14 (57.14%)	10	7/16 (43.75%)	15
Dry Skin ^† 1	3/14 (21.43%)	3	5/16 (31.25%)	11
Pruritus ^† 1	0/14 (0.00%)	0	2/16 (12.50%)	2
Rash ^† 1	2/14 (14.29%)	2	3/16 (18.75%)	4
Nail discoloration ^† 1	1/14 (7.14%)	1	2/16 (12.50%)	8
Vascular disorders
Hot Flashes ^† 1	7/14 (50.00%)	8	10/16 (62.50%)	28
Hypertension ^† 1	8/14 (57.14%)	14	9/16 (56.25%)	12
1 Term from vocabulary, MedDRA 10.0 † Indicates events were collected by systematic assessment * Indicates events were collected by non-systematic assessment

Limitations and Caveats

The study was terminated early due to slow accrual.

More Information

Certain Agreements

All Principal Investigators ARE employed by the organization sponsoring the study.

Results Point of Contact

Layout table for Results Point of Contact information

Name/Title:	Stacy Kehoe
Organization:	Avera
Phone:	605.322.3082
EMail:	Stacy.Kehoe@avera.org

Layout table for additonal information

Responsible Party:	Avera McKennan Hospital & University Health Center
ClinicalTrials.gov Identifier:	NCT02472353
Other Study ID Numbers:	AMEM-2014-MET001
First Submitted:	June 9, 2015
First Posted:	June 15, 2015
Results First Submitted:	September 5, 2019
Results First Posted:	October 16, 2019
Last Update Posted:	October 16, 2019

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