Trial Outcomes & Findings for Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin (NCT NCT02096588)

NCT ID: NCT02096588

Last Updated: 2024-07-09

Results Overview

To compare the absolute change in echocardiographic GLS (Global Longitudinal Strain) from baseline (T0) to 2-3 weeks after (T2) completion of 4 cycles of (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who do and do not receive concurrent simvastatin therapy

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

34 participants

Primary outcome timeframe

up to 15 weeks

Results posted on

2024-07-09

Participant Flow

27 -Hopkins 7 - Sibley memorial (DC)

3 subjects were screen failures, therefore 31 subjects were assigned to a treatment group in study

Participant milestones

Participant milestones
Measure	Simvastatin Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Overall Study STARTED	15	16
Overall Study COMPLETED	13	15
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Simvastatin Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Overall Study Lack of Efficacy	2	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Detection and Prevention of Anthracycline-Related Cardiac Toxicity With Concurrent Simvastatin

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Simvastatin n=15 Participants Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug n=16 Participants Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	Total n=31 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	14 Participants n=5 Participants	16 Participants n=7 Participants	30 Participants n=5 Participants
Age, Categorical >=65 years	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Sex: Female, Male Female	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	15 Participants n=5 Participants	15 Participants n=7 Participants	30 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	5 Participants n=5 Participants	5 Participants n=7 Participants	10 Participants n=5 Participants
Race (NIH/OMB) White	8 Participants n=5 Participants	11 Participants n=7 Participants	19 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Region of Enrollment United States	15 Participants n=5 Participants	16 Participants n=7 Participants	31 Participants n=5 Participants

PRIMARY outcome

Timeframe: up to 15 weeks

Population: Only participants with GLS measured on both T0 and T2 echocardiograms were evaluable for this outcome measure. Therefore, data was evaluable in only 27/31 participants for this outcome measure.

Outcome measures

Outcome measures
Measure	Simvastatin n=13 Participants Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug n=14 Participants Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Change in Echocardiographic Global Longitudinal Strain (GLS)	0.42 Percentage change in GLS Standard Deviation 2.46	1.11 Percentage change in GLS Standard Deviation 3.67

SECONDARY outcome

Timeframe: 52 weeks

Population: Adverse event data was not collected from the "No drug" arm.

Number of participants with concurrent administration of simvastatin with (neo)adjuvant anthracycline-based chemotherapy in early stage breast cancer patients who experience adverse events as defined by NCI CTCAE v4.0.

Outcome measures

Outcome measures
Measure	Simvastatin n=15 Participants Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Number of Participants With Adverse Events as a Measure of Safety and Tolerability	15 Participants	—

SECONDARY outcome

Timeframe: 5 years

Population: Data was not collected

To describe the recurrence free survival (RFS) in early stage breast cancer patients treated with anthracycline-based chemotherapy with and without concurrent simvastatin

Outcome measures

Outcome data not reported

Adverse Events

Simvastatin

Serious events: 1 serious events

Other events: 13 other events

Deaths: 1 deaths

No Drug

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Simvastatin n=15 participants at risk Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Investigations CPK increased	6.7% 1/15 • Number of events 1 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.	— 0/0 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.

Other adverse events

Other adverse events
Measure	Simvastatin n=15 participants at risk Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Treatment will start 7 days prior to the planned doxorubicin/cyclophosphamide chemotherapy initiation and will continue for a total of 25 weeks. Simvastatin: Simvastatin will be administered on an outpatient basis orally at a dose of 40 mg once daily. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.	No Drug Participant not randomized to simvastatin will participate in all aspects of the study, including planned doxorubicin/cyclophosphamide chemotherapy, with the exception of simvastatin administration. Doxorubicin/cyclophosphamide: The standard chemotherapy regimen that must be planned for all participants in order to take part in this study. The regimen is given every 2 or 3 weeks per standard of care, at the direction of the treating physician.
Investigations Alanine aminotransferase increased	46.7% 7/15 • Number of events 10 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.	— 0/0 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.
Respiratory, thoracic and mediastinal disorders Dyspnea	13.3% 2/15 • Number of events 2 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.	— 0/0 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.
General disorders Generalized Edema	13.3% 2/15 • Number of events 3 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.	— 0/0 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.
General disorders Fatigue	6.7% 1/15 • Number of events 1 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.	— 0/0 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.
Gastrointestinal disorders Constipation	6.7% 1/15 • Number of events 1 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.	— 0/0 • up to 30 days after last dose of simvastatin, up to 1 year Adverse events (AEs) were not monitored for participants in the "No Drug" arm (0 participants at risk). Only AEs possibly-related to simvastatin were recorded. The collection of toxicities related to chemotherapy and other breast cancer therapy administration was not monitored. Changes in EF or the development of other concerning findings on echocardiograms was also closely monitored.

Additional Information

Dr. Karen Smith ; Clinical Associate

SKCCC SOM Onc Breast and Ovarian Cancer

Phone: 2026606500

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place