Trial Outcomes & Findings for Metformin Hydrochloride and Doxycycline in Treating Patients With Localized Breast or Uterine Cancer (NCT NCT02874430)
NCT ID: NCT02874430
Last Updated: 2026-04-22
Results Overview
Caveolin-1 (CAV1) expression in stromal cells is assessed by immunohistochemistry using a standard intensity scale of 0 to 3+, where 0 indicates no staining and 1+, 2+, and 3+ indicate increasing levels of staining intensity. For this measure, stromal cells with CAV1 staining of 1+ or higher are considered positive. Results are reported as the percentage of positive stromal cells, ranging from 0% (no positive cells) to 100% (all cells positive). Higher percentages indicate a worse outcome, as higher CAV1 expression is associated with more aggressive tumor behavior. Within-patient changes will be analyzed using the Wilcoxon signed-rank test.
TERMINATED
PHASE2
29 participants
Pre-treatment (Baseline) and Post-treatment (week 6)
2026-04-22
Participant Flow
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
Participant milestones
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Overall Study
STARTED
|
29
|
|
Overall Study
COMPLETED
|
27
|
|
Overall Study
NOT COMPLETED
|
2
|
Reasons for withdrawal
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Overall Study
Lost to Follow-up
|
2
|
Baseline Characteristics
Metformin Hydrochloride and Doxycycline in Treating Patients With Localized Breast or Uterine Cancer
Baseline characteristics by cohort
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=29 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=60 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
29 Participants
n=60 Participants
|
|
Age, Categorical
>=65 years
|
0 Participants
n=60 Participants
|
|
Sex: Female, Male
Female
|
29 Participants
n=60 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
2 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
27 Participants
n=60 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Asian
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Black or African American
|
9 Participants
n=60 Participants
|
|
Race (NIH/OMB)
White
|
18 Participants
n=60 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=60 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
2 Participants
n=60 Participants
|
|
Region of Enrollment
United States
|
29 participants
n=60 Participants
|
PRIMARY outcome
Timeframe: Pre-treatment (Baseline) and Post-treatment (week 6)Population: Only 10 patients had sufficient paired tumor specimens for primary outcome comparison. Post-treatment samples with extensive necrosis or no viable tumor were excluded due to lack of identifiable stroma. This single-arm study treated all participants uniformly. Patients with breast, uterine, and cervical cancers were analyzed as a combined population, as cohorts were not powered or intended for independent comparisons.
Caveolin-1 (CAV1) expression in stromal cells is assessed by immunohistochemistry using a standard intensity scale of 0 to 3+, where 0 indicates no staining and 1+, 2+, and 3+ indicate increasing levels of staining intensity. For this measure, stromal cells with CAV1 staining of 1+ or higher are considered positive. Results are reported as the percentage of positive stromal cells, ranging from 0% (no positive cells) to 100% (all cells positive). Higher percentages indicate a worse outcome, as higher CAV1 expression is associated with more aggressive tumor behavior. Within-patient changes will be analyzed using the Wilcoxon signed-rank test.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=10 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Change in the Percentage of Stromal Cells Expressing Caveolin-1 (CAV1) at an Intensity of 1+ or Greater by Immunohistochemistry
Pre-treatment
|
61 percentage of cells
Interval 25.0 to 75.0
|
|
Change in the Percentage of Stromal Cells Expressing Caveolin-1 (CAV1) at an Intensity of 1+ or Greater by Immunohistochemistry
Post-treatment
|
58.3 percentage of cells
Interval 25.0 to 75.0
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
Incidence of adverse events evaluated using National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=29 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Number of Adverse Events
|
18 adverse events
|
SECONDARY outcome
Timeframe: at 5 weeksPopulation: No participants were analyzed for this outcome. Post-treatment tumor specimens lacked sufficient stromal tissue to allow evaluation of MCT4 expression. No additional tissue specimens are available and this outcome will not be assessed in the future.
Analysis will be performed separately in breast and uterine cancer patients. Evaluated using Aperio analyses of expression intensity with previously validated algorithms. Analysis will be performed using the Wilcoxon signed-rank test.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: at 5 weeksPopulation: No participants were analyzed for this outcome. Post-treatment tumor specimens lacked sufficient stromal tissue to allow evaluation of TOMM20. No additional tissue specimens are available and this outcome will not be assessed in the future.
Analysis was performed in breast and uterine cancer patients together due to lower than expected tumor viability.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: 5 weeksPopulation: No participants were analyzed for this outcome. Post-treatment tumor specimens lacked sufficient stromal tissue for allow evaluation. No additional tissue specimens are available and this outcome will not be assessed in the future.
Assessed in relation to the percentage of cells expressing Estrogen Receptor (ER) and Progesterone Receptor (PR) for breast and uterine samples and Human Epidermal Growth Factor Receptor 2 (HER2) in breast cancer samples.
Outcome measures
Outcome data not reported
SECONDARY outcome
Timeframe: Pre-treatment (Baseline) and Post-treatment (week 6)Population: Only 10 patients had sufficient tumor tissue for primary outcome comparisons. Samples with extensive necrosis or no viable tumor were not analyzable. Due to limited viability, CAV1 was prioritized, followed by MCT1, MCT4, and TOMM20, resulting in tissue exhaustion. This single-arm study analyzed breast, uterine, and cervical cancers as a combined population, as cohorts were not powered or intended for independent comparisons.
Analyzed breast and uterine cancer patients together due to low tumor viability. Mean scores and full range are provided. Expression is reported as the percentage of tumor cells staining on a positive scale from 0-100%, where higher percentages indicate greater MCT1 expression. Pre-treatment and post treatment samples were compared.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=10 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Percentage of Tumor Cells That Express Monocarboxylate Transporter 1 (MCT1)
pre-treatment
|
41.6 percentage of cells
Interval 10.0 to 50.0
|
|
Percentage of Tumor Cells That Express Monocarboxylate Transporter 1 (MCT1)
post-treatment
|
38.9 percentage of cells
Interval 10.0 to 75.0
|
SECONDARY outcome
Timeframe: 1 yearPopulation: All participants included in the analysis did not have progression observed. This was a single-arm study in which all participants received the same intervention. Patients with breast, uterine, and cervical cancers were analyzed as a single population. Although enrollment targets were set by disease cohort, these groups were not intended or powered for independent comparisons, so results are reported for the combined population.
The time from the start of treatment until disease progression or death from any cause, whichever occurs first. The number of participants who experienced progression or death during the follow up period is reported.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=27 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Progression-free Survival
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
The time from the start of treatment until death from any cause. The number of participants who died during the 12 month follow up period.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=27 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Overall Survival (OS)
|
0 Participants
|
SECONDARY outcome
Timeframe: 12 monthsPopulation: This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
The number of participants with clinical improvement in disease status following treatment. Clinical response is defined as the continued eligibility for the surgical procedure as initially planned at the time of trial enrollment.
Outcome measures
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=27 Participants
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Clinical Response Rate
|
27 Participants
|
Adverse Events
Treatment (Metformin Hydrochloride, Doxycycline)
Serious adverse events
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=29 participants at risk
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Blood and lymphatic system disorders
Thrombocytopenia - Grade 4
|
3.4%
1/29 • Number of events 2 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
Other adverse events
| Measure |
Treatment (Metformin Hydrochloride, Doxycycline)
n=29 participants at risk
Patients receive metformin hydrochloride orally daily on days 1-3 and twice a day starting on day 4. Patients also receive doxycycline orally every 12 hours starting on day 1. Treatment repeats every 7 days for up to 2 courses in the absence of disease progression or unacceptable toxicity.
Metformin Hydrochloride: Given orally
Doxycycline: Given orally
|
|---|---|
|
Gastrointestinal disorders
diarrhea - grade 1
|
10.3%
3/29 • Number of events 4 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
diarrhea - grade 2
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
vomiting
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
nausea
|
6.9%
2/29 • Number of events 2 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
General disorders
Fatigue
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
Constipation
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Renal and urinary disorders
Hematuria
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
stomach pain
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
dyspepsia - grade 1
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
dyspepsia - grade 2
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Gastrointestinal disorders
upset stomach
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
|
Renal and urinary disorders
urinary frequency
|
3.4%
1/29 • Number of events 1 • Subjects were monitored for adverse events for up to five weeks prior to surgical resection, then for 12 months. AE data is collected until the 1 year follow up post surgery.
This was a single-arm study in which all participants received the same intervention. Participants included patients with breast, uterine, and cervical cancers, which were treated as subgroups within a single analysis population. While the protocol specified enrollment targets by disease cohort, these cohorts were not intended to function as independent comparison groups, and the study was not powered for separate analyses. Accordingly, results are reported for the combined population.
|
Additional Information
Jennifer Johnson, MD, PhD, FACP
Thomas Jefferson University
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place