Trial Outcomes & Findings for Metformin Hydrochloride and Doxycycline in Treating Patients With Head and Neck Squamous Cell Carcinoma (NCT NCT03076281)
NCT ID: NCT03076281
Last Updated: 2026-01-29
Results Overview
Within-patient change in IHC scores will be analyzed using the Wilcoxon signed-rank test. Comparisons will be made between pretreatment and post-treatment within each of the cohorts. Caveolin-1 (CAV1) immunohistochemistry (IHC) will be performed on pre- and post-treatment tumor specimens. The mean percentage of fibroblasts expressing CAV1 will be compared before and after treatment.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
7 participants
Primary outcome timeframe
Baseline to 30 days after last drug dose
Results posted on
2026-01-29
Participant Flow
Participant milestones
| Measure |
Arm A (Metformin Hydrochloride)
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Overall Study
STARTED
|
3
|
2
|
2
|
|
Overall Study
COMPLETED
|
3
|
1
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
1
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Metformin Hydrochloride and Doxycycline in Treating Patients With Head and Neck Squamous Cell Carcinoma
Baseline characteristics by cohort
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
Total
n=7 Participants
Total of all reporting groups
|
|---|---|---|---|---|
|
Age, Categorical
<=18 years
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Age, Categorical
Between 18 and 65 years
|
0 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
1 Participants
n=8687 Participants
|
2 Participants
n=153 Participants
|
|
Age, Categorical
>=65 years
|
3 Participants
n=35 Participants
|
1 Participants
n=4328 Participants
|
1 Participants
n=8687 Participants
|
5 Participants
n=153 Participants
|
|
Sex: Female, Male
Female
|
2 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
2 Participants
n=153 Participants
|
|
Sex: Female, Male
Male
|
1 Participants
n=35 Participants
|
2 Participants
n=4328 Participants
|
2 Participants
n=8687 Participants
|
5 Participants
n=153 Participants
|
|
Ethnicity (NIH/OMB)
Hispanic or Latino
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Ethnicity (NIH/OMB)
Not Hispanic or Latino
|
3 Participants
n=35 Participants
|
2 Participants
n=4328 Participants
|
2 Participants
n=8687 Participants
|
7 Participants
n=153 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
American Indian or Alaska Native
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Asian
|
1 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
1 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Black or African American
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
White
|
2 Participants
n=35 Participants
|
2 Participants
n=4328 Participants
|
2 Participants
n=8687 Participants
|
6 Participants
n=153 Participants
|
|
Race (NIH/OMB)
More than one race
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Race (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=35 Participants
|
0 Participants
n=4328 Participants
|
0 Participants
n=8687 Participants
|
0 Participants
n=153 Participants
|
|
Region of Enrollment
United States
|
3 participants
n=35 Participants
|
2 participants
n=4328 Participants
|
2 participants
n=8687 Participants
|
7 participants
n=153 Participants
|
PRIMARY outcome
Timeframe: Baseline to 30 days after last drug doseWithin-patient change in IHC scores will be analyzed using the Wilcoxon signed-rank test. Comparisons will be made between pretreatment and post-treatment within each of the cohorts. Caveolin-1 (CAV1) immunohistochemistry (IHC) will be performed on pre- and post-treatment tumor specimens. The mean percentage of fibroblasts expressing CAV1 will be compared before and after treatment.
Outcome measures
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Change in Percentage of CFS Expressing Caveolin-1 at an Intensity of 1+ or Greater Assessed in Tumor-associated Stroma Cells by Immunohistochemistry
|
32.5 percentage of cells
Interval 20.0 to 80.0
|
30 percentage of cells
Interval 30.0 to 60.0
|
32.5 percentage of cells
Interval 20.0 to 70.0
|
SECONDARY outcome
Timeframe: Up to 30 days after last drug dose: approximately1 yearSafety will be provided in descriptive tables as Incidence of adverse events as assessed by National Cancer Institute Common Terminology Criteria for Adverse Events version 4.0.
Outcome measures
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Incidence of Adverse Events as Assessed by National Cancer Institute Common Terminology Criteria for Adverse Events Version 4.0
|
5 adverse events
|
6 adverse events
|
3 adverse events
|
SECONDARY outcome
Timeframe: Baseline to 30 days after last drug doseImmunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Outcome measures
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express BGAL
|
0 Percentage of tumor cells
Interval 0.0 to 0.0
|
12.5 Percentage of tumor cells
Interval 0.0 to 25.0
|
12.5 Percentage of tumor cells
Interval 0.0 to 25.0
|
SECONDARY outcome
Timeframe: Baseline to 30 days after last drug doseImmunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Outcome measures
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT1
|
7.5 Percentage of tumor cells
Interval 0.0 to 15.0
|
7.5 Percentage of tumor cells
Interval 0.0 to 15.0
|
2.5 Percentage of tumor cells
Interval 0.0 to 5.0
|
SECONDARY outcome
Timeframe: Baseline to 30 days after last drug doseImmunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Outcome measures
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express MCT4
|
0 Percentage of tumor cells
Interval 0.0 to 0.0
|
12.5 Percentage of tumor cells
Interval 0.0 to 25.0
|
12.5 Percentage of tumor cells
Interval 0.0 to 25.0
|
SECONDARY outcome
Timeframe: Baseline to 30 days after last drug doseImmunohistochemistry will be performed for Caveolin-1, TUNEL, BGAL, MCT1, MCT4, and TOMM20 on the pre- and post- treatment specimens and evaluated for staining distribution and intensity by two blinded pathologists.
Outcome measures
| Measure |
Arm A (Metformin Hydrochloride)
n=3 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 Participants
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 Participants
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Change in Percent of Tumor Cells Expressing MCT4, That Are TUNEL Positive and That Express TOMM20
|
12.5 Percentage of tumor cells
Interval 0.0 to 25.0
|
12.5 Percentage of tumor cells
Interval 0.0 to 25.0
|
0 Percentage of tumor cells
Interval 0.0 to 0.0
|
Adverse Events
Arm A (Metformin Hydrochloride)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Arm B (Doxycycline)
Serious events: 1 serious events
Other events: 2 other events
Deaths: 1 deaths
Arm C (Metformin Hydrochloride, Doxycycline)
Serious events: 0 serious events
Other events: 1 other events
Deaths: 1 deaths
Serious adverse events
| Measure |
Arm A (Metformin Hydrochloride)
n=3 participants at risk
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 participants at risk
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 participants at risk
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Gastrointestinal disorders
Dysphagia
|
0.00%
0/3 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
|
Infections and infestations
Wound Infection
|
0.00%
0/3 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
|
General disorders
Hypocalcemia
|
0.00%
0/3 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
Other adverse events
| Measure |
Arm A (Metformin Hydrochloride)
n=3 participants at risk
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery in the absence of disease progression or unacceptable toxicity
Metformin Hydrochloride: Given orally
|
Arm B (Doxycycline)
n=2 participants at risk
Patients receive doxycycline PO every 12 hours on days 1 to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Doxycycline: Given orally
|
Arm C (Metformin Hydrochloride, Doxycycline)
n=2 participants at risk
Patients receive metformin hydrochloride PO daily on days 1-3 and twice daily starting on day 4 to the day prior to surgery and doxycycline PO every 12 hours on days 1to the day prior to surgery in the absence of disease progression or unacceptable toxicity.
Metformin +Doxycycline: Given orally
|
|---|---|---|---|
|
Gastrointestinal disorders
Dysphagia
|
66.7%
2/3 • Number of events 2 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
|
General disorders
Edema
|
33.3%
1/3 • Number of events 1 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
50.0%
1/2 • Number of events 2 • 1 year
|
|
General disorders
Neck Pain
|
66.7%
2/3 • Number of events 2 • 1 year
|
50.0%
1/2 • Number of events 1 • 1 year
|
0.00%
0/2 • 1 year
|
Additional Information
Dr. Jennifer Johnson
Sidney Kimmel Cancer Center at Thomas Jefferson University
Phone: 215-955-8875
Email: [email protected]
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place