Trial Outcomes & Findings for ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment (NCT NCT02917629)
NCT ID: NCT02917629
Last Updated: 2023-03-08
Results Overview
Baseline, post-exposure, absolute change in Ki-67, and difference in absolute change between the ACTOplus met XR and placebo subjects will all be summarized with descriptive statistics. Ki-67 is a semi-quantitative immune-histochemistry analysis in which a computer generates an analysis based on the staining within tumor and normal cells leading to a score which is an indirect measure of cellular proliferation. Will compare the difference in absolute change in Ki-67 between the ACTOplus met XR and placebo arms using a two sided two-sample Student's t-test or Wilcoxon rank-sum test, as appropriate, at a significance level of 0.05.
Recruitment status
TERMINATED
Study phase
PHASE2
Target enrollment
6 participants
Primary outcome timeframe
Baseline to days 11-22
Results posted on
2023-03-08
Participant Flow
Participants were enrolled from Johns Hopkins University - Sidney Kimmel Comprehensive Cancer Center, UW Hospital and Clinics, and University of Minnesota - Masonic Cancer Center between May 31, 2018 and August 2, 2019.
16 people were consented and 10 people were subsequently determined to be ineligible. 6 participants were randomized to study.
Participant milestones
| Measure |
Group I (ACTOplus Met XR)
Patients receive ACTOplus met extended release (XR) by mouth (PO) once a day (QD) for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Overall Study
STARTED
|
4
|
2
|
|
Overall Study
Considered Study Compliant
|
4
|
1
|
|
Overall Study
Experienced Study Drug Interruption
|
2
|
1
|
|
Overall Study
COMPLETED
|
4
|
1
|
|
Overall Study
NOT COMPLETED
|
0
|
1
|
Reasons for withdrawal
| Measure |
Group I (ACTOplus Met XR)
Patients receive ACTOplus met extended release (XR) by mouth (PO) once a day (QD) for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Overall Study
Withdrawal by Subject
|
0
|
1
|
Baseline Characteristics
ACTOplus Met XR in Treating Patients With Stage I-IV Oral Cavity or Oropharynx Cancer Undergoing Definitive Treatment
Baseline characteristics by cohort
| Measure |
Group I (ACTOplus Met XR)
n=4 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
Total
n=6 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
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
Age, Categorical
>=65 years
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
Sex: Female, Male
Female
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 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
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
Ethnicity (NIH/OMB)
Unknown or Not Reported
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Race (NIH/OMB)
White
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 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
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
United States
|
4 participants
n=5 Participants
|
2 participants
n=7 Participants
|
6 participants
n=5 Participants
|
|
ECOG Performance Status
0 (Fully Active)
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
ECOG Performance Status
1 (Restricted)
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Systolic Blood Pressure
|
141.75 mmHg
n=5 Participants
|
135.00 mmHg
n=7 Participants
|
139.50 mmHg
n=5 Participants
|
|
Diastolic Blood Pressure
|
80.00 mmHg
n=5 Participants
|
86.00 mmHg
n=7 Participants
|
82.00 mmHg
n=5 Participants
|
|
Pulse
|
66.00 beats per minute
n=5 Participants
|
79.00 beats per minute
n=7 Participants
|
70.34 beats per minute
n=5 Participants
|
|
Temperature
|
97.92 degrees Fahrenheit (F)
n=5 Participants
|
98.05 degrees Fahrenheit (F)
n=7 Participants
|
97.96 degrees Fahrenheit (F)
n=5 Participants
|
|
Height
|
171.48 centimeters
n=5 Participants
|
180.00 centimeters
n=7 Participants
|
174.32 centimeters
n=5 Participants
|
|
Weight
|
88.64 kilograms
n=5 Participants
|
93.67 kilograms
n=7 Participants
|
90.32 kilograms
n=5 Participants
|
|
Body Mass Index (BMI)
|
30.17 kilograms per meter squared
n=5 Participants
|
28.70 kilograms per meter squared
n=7 Participants
|
29.68 kilograms per meter squared
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Gastrointestinal
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Head, Eyes, Ears, Nose, Throat
|
4 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
6 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Musculoskeletal
|
3 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
5 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Cardiovascular
|
3 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Endocrine / Metabolic
|
2 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Genitourinary
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Respiratory
|
4 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
4 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Dermatologic
|
0 Participants
n=5 Participants
|
2 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Neurologic
|
1 Participants
n=5 Participants
|
1 Participants
n=7 Participants
|
2 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Hematopoietic / Lymph
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Neck
|
1 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
1 Participants
n=5 Participants
|
|
History or Baseline Presence of Abnormality or Disease
Breasts
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
PRIMARY outcome
Timeframe: Baseline to days 11-22Population: 1 sample in the treatment group was not analyzed because site misplaced the sample.
Baseline, post-exposure, absolute change in Ki-67, and difference in absolute change between the ACTOplus met XR and placebo subjects will all be summarized with descriptive statistics. Ki-67 is a semi-quantitative immune-histochemistry analysis in which a computer generates an analysis based on the staining within tumor and normal cells leading to a score which is an indirect measure of cellular proliferation. Will compare the difference in absolute change in Ki-67 between the ACTOplus met XR and placebo arms using a two sided two-sample Student's t-test or Wilcoxon rank-sum test, as appropriate, at a significance level of 0.05.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=3 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Absolute Change in Proliferation Index (Ki-67) Expression, Assessed in Tumor Tissue by Immunohistochemistry
baseline
|
20.40 proliferation index expression
Interval 19.84 to 25.1
|
13.69 proliferation index expression
Interval 12.91 to 14.46
|
|
Absolute Change in Proliferation Index (Ki-67) Expression, Assessed in Tumor Tissue by Immunohistochemistry
Day 11-22
|
17.57 proliferation index expression
Interval 17.17 to 17.64
|
36.96 proliferation index expression
Interval 36.96 to 36.96
|
|
Absolute Change in Proliferation Index (Ki-67) Expression, Assessed in Tumor Tissue by Immunohistochemistry
absolute change from baseline
|
-2.68 proliferation index expression
Interval -7.46 to -2.6
|
24.82 proliferation index expression
Interval 24.82 to 24.82
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: 1 sample in the treatment group was not analyzed because site misplaced the sample.
Will be summarized for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=3 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Change in Ki-67 Expression in Visually Normal Appearing Tissue, Assessed by Immunohistochemistry
baseline
|
17.58 proliferation index expression
Interval 15.18 to 17.68
|
14.52 proliferation index expression
Interval 11.66 to 17.38
|
|
Change in Ki-67 Expression in Visually Normal Appearing Tissue, Assessed by Immunohistochemistry
Day 11-22
|
11.81 proliferation index expression
Interval 10.02 to 14.23
|
26.05 proliferation index expression
Interval 26.05 to 26.05
|
|
Change in Ki-67 Expression in Visually Normal Appearing Tissue, Assessed by Immunohistochemistry
absolute change from baseline
|
-5.77 proliferation index expression
Interval -7.66 to -0.95
|
17.25 proliferation index expression
Interval 17.25 to 17.25
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: 1 sample in the treatment group was not analyzed because site misplaced the sample.
Cleaved Caspase 3 is a semi-quantitative immune-histochemistry analysis in which a computer generates an analysis based on the staining within tumor and normal cells leading to a score which is a direct measure of cellular apoptosis. Will be summarized for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=3 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Change in Cleaved Caspase 3 Expression in Visually Normal Appearing Tissue and Tumor Tissue Samples, Assessed by Immunohistochemistry
Baseline Tumor Tissue
|
1.000 percent positive cells
Standard Deviation 1.000
|
1.000 percent positive cells
Standard Deviation 0.000
|
|
Change in Cleaved Caspase 3 Expression in Visually Normal Appearing Tissue and Tumor Tissue Samples, Assessed by Immunohistochemistry
Post-Exposure Tumor Tissue
|
3.333 percent positive cells
Standard Deviation 4.041
|
4.000 percent positive cells
Standard Deviation NA
only 1 participant measured
|
|
Change in Cleaved Caspase 3 Expression in Visually Normal Appearing Tissue and Tumor Tissue Samples, Assessed by Immunohistochemistry
Baseline Normal Tissue
|
0.000 percent positive cells
Standard Deviation 0.000
|
0.000 percent positive cells
Standard Deviation 0.000
|
|
Change in Cleaved Caspase 3 Expression in Visually Normal Appearing Tissue and Tumor Tissue Samples, Assessed by Immunohistochemistry
Post-Exposure Normal Tissue
|
0.000 percent positive cells
Standard Deviation 0.000
|
0.000 percent positive cells
Standard Deviation NA
only 1 participant measured
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: 1 sample in the treatment group was not analyzed because site misplaced the sample.
Will be summarized for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=3 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Cyclin D1 Baseline
|
0.051 percent positive cells
Interval 0.039 to 0.062
|
0.020 percent positive cells
Interval 0.014 to 0.025
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Cyclin D1 Day 11-22
|
0.050 percent positive cells
Interval 0.044 to 0.086
|
0.033 percent positive cells
Interval 0.033 to 0.033
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Absolute change in Cyclin D1 from Baseline
|
-0.0066 percent positive cells
Interval -0.021 to 0.0079
|
0.0019 percent positive cells
Interval 0.0019 to 0.0019
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
P21 Baseline
|
0.090 percent positive cells
Interval 0.077 to 0.166
|
0.112 percent positive cells
Interval 0.112 to 0.112
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
P21 Day 11-22
|
0.068 percent positive cells
Interval 0.066 to 0.07
|
0.052 percent positive cells
Interval 0.052 to 0.052
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Absolute change in P21 from Baseline
|
-0.0093 percent positive cells
Interval -0.014 to -0.0049
|
-0.0605 percent positive cells
Interval -0.0605 to -0.0605
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Phosphorylated AKT Baseline
|
0.00018 percent positive cells
Interval 0.00015 to 0.00442
|
0.00013 percent positive cells
Interval 0.000067 to 0.0002
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Phosphorylated AKT Day 11-22
|
0.00048 percent positive cells
Interval 0.00025 to 0.00481
|
0.00042 percent positive cells
Interval 0.00042 to 0.00042
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Absolute change in phosphorylated AKT from baseline
|
0.00031 percent positive cells
Interval 0.0001 to 0.00039
|
0.00016 percent positive cells
Interval 0.00016 to 0.00016
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Phosphorylated AMPK at Baseline
|
0.079 percent positive cells
Interval 0.075 to 0.088
|
0.363 percent positive cells
Interval 0.363 to 0.363
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Phosphorylated AMPK Day 11-22
|
0.131 percent positive cells
Interval 0.103 to 0.134
|
0.030 percent positive cells
Interval 0.03 to 0.03
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Absolute change in phosphorylated AMPK from baseline
|
0.052 percent positive cells
Interval 0.015 to 0.06
|
-0.333 percent positive cells
Interval -0.333 to -0.333
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
PPAR gamma at Baseline
|
0.0547 percent positive cells
Interval 0.0286 to 0.066
|
0.0138 percent positive cells
Interval 0.0072 to 0.02
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
PPAR gamma Day 11-22
|
0.0061 percent positive cells
Interval 0.0056 to 0.02
|
0.0200 percent positive cells
Interval 0.02 to 0.02
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Absolute change in PPAR gamma from baseline
|
-0.022 percent positive cells
Interval -0.047 to -0.0091
|
0.019 percent positive cells
Interval 0.019 to 0.0194
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Phosphorylated S6 at Baseline
|
0.284 percent positive cells
Interval 0.188 to 0.339
|
0.188 percent positive cells
Interval 0.143 to 0.232
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Phosphorylated S6 Day 11-22
|
0.282 percent positive cells
Interval 0.226 to 0.298
|
0.071 percent positive cells
Interval 0.071 to 0.071
|
|
Change in Cyclin D1, p21 and Biguanide or Phosphorylated AKT, Phosphorylated AMPK, Phosphorylated S6 (Metformin), and PPAR Gamma Expression, Assessed by Immunohistochemistry
Absolute change in phosphorylated S6 from Baseline
|
0.029 percent positive cells
Interval -0.098 to 0.11
|
-0.028 percent positive cells
Interval -0.028 to -0.028
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: 1 sample in the treatment group was not analyzed because site misplaced the sample.
Will be summarized for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=3 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
CD68 Baseline
|
0.11 percent positive cells
Interval 0.07 to 0.14
|
0.190 percent positive cells
Interval 0.175 to 0.21
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
CD68 Day 11-22
|
0.10 percent positive cells
Interval 0.074 to 0.11
|
0.23 percent positive cells
Interval 0.227 to 0.23
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
Absolute Change in CD68 from Baseline
|
-0.033 percent positive cells
Interval -0.055 to -0.01
|
0.068 percent positive cells
Interval 0.068 to 0.068
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
PD1 Baseline
|
0.0520 percent positive cells
Interval 0.0439 to 0.153
|
0.0356 percent positive cells
Interval 0.029 to 0.042
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
PD1 Day 11-22
|
0.0088 percent positive cells
Interval 0.0081 to 0.017
|
0.0721 percent positive cells
Interval 0.0721 to 0.0721
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
Absolute Change in PD1 from Baseline
|
-0.045 percent positive cells
Interval -0.15 to -0.027
|
0.050 percent positive cells
Interval 0.05 to 0.05
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
PD-L1 Baseline
|
0.0632 percent positive cells
Interval 0.0335 to 0.093
|
0.0086 percent positive cells
Interval 0.0051 to 0.012
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
PD-L1 Day 11-22
|
0.0494 percent positive cells
Interval 0.0263 to 0.051
|
0.0136 percent positive cells
Interval 0.0136 to 0.0136
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
Absolute Change in PD-L1 from Baseline
|
-0.012 percent positive cells
Interval -0.043 to 0.019
|
0.012 percent positive cells
Interval 0.012 to 0.012
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
CD8 Baseline
|
0.244 percent positive cells
Interval 0.18 to 0.31
|
0.141 percent positive cells
Interval 0.122 to 0.16
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
CD8 Day 11-22
|
0.095 percent positive cells
Interval 0.066 to 0.12
|
0.189 percent positive cells
Interval 0.189 to 0.19
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
Absolute Change in CD8 from Baseline
|
-0.218 percent positive cells
Interval -0.218 to -0.218
|
0.086 percent positive cells
Interval 0.086 to 0.086
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
CD4 Baseline
|
0.193 percent positive cells
Interval 0.114 to 0.204
|
0.195 percent positive cells
Interval 0.191 to 0.198
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
CD4 Day 11-22
|
0.159 percent positive cells
Interval 0.118 to 0.332
|
0.074 percent positive cells
Interval 0.074 to 0.074
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
Absolute Change in CD4 from Baseline
|
0.043 percent positive cells
Interval -0.0064 to 0.18
|
-0.128 percent positive cells
Interval -0.128 to -0.128
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
FoxP3 Baseline
|
0.027 percent positive cells
Interval 0.015 to 0.035
|
0.057 percent positive cells
Interval 0.036 to 0.079
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
FoxP3 Day 11-22
|
0.020 percent positive cells
Interval 0.014 to 0.025
|
0.038 percent positive cells
Interval 0.038 to 0.038
|
|
Change in Regulatory T Cell, T4, T8, Tumor-associated Macrophage-CD68 Positive, PD1, PD-L1 Expression, Assessed in Tumor Tissue by Immunohistochemistry
Absolute Change in FoxP3 from Baseline
|
0.0034 percent positive cells
Interval -0.01 to 0.0041
|
0.0235 percent positive cells
Interval 0.0235 to 0.0235
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: Pre- and post-treatment RNA-seq data was available in four ACTOplus treated participants and one placebo treated participant. Because of this, a comparison between the treatment arms was not deemed to be possible or useful. What was attempted was an analysis of change from baseline values for the ACTOplus met® XR arm.
Will be summarized for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=37769 genes
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=37769 genes
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Genes With Significant Changes From Baseline to Days 11-22 in Tumor Tissue in Treated Participants: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000229822
|
1.0011 raw counts of RNA sequencing reads
Standard Deviation 0.0240
|
-5.0023 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
|
Genes With Significant Changes From Baseline to Days 11-22 in Tumor Tissue in Treated Participants: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000230585
|
-1.0217 raw counts of RNA sequencing reads
Standard Deviation 0.0257
|
-3.0108 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
|
Genes With Significant Changes From Baseline to Days 11-22 in Tumor Tissue in Treated Participants: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000249245
|
-1.0098 raw counts of RNA sequencing reads
Standard Deviation 0.0050
|
0.0000 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
|
Genes With Significant Changes From Baseline to Days 11-22 in Tumor Tissue in Treated Participants: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000261792
|
1.0007 raw counts of RNA sequencing reads
Standard Deviation 0.0063
|
0.0000 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: Pre- and post-treatment RNA-seq data was available in four ACTOplus treated participants and one placebo treated participant. Because of this, a comparison between the treatment arms was not deemed to be possible or useful. What was attempted was an analysis of change from baseline values for the ACTOplus met® XR arm.
Will be summarized for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=1 genes
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=1 genes
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Genes With Significant Changes From Baseline to Days 11-22 for Normal Tissue: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
|
1.0060 raw counts of RNA sequencing reads
Standard Deviation 0.0060
|
2.0135 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
SECONDARY outcome
Timeframe: Baseline to days 11-22Population: Pre- and post-treatment RNA-seq data was available in four ACTOplus treated participants and one placebo treated participant. Because of this, a comparison between the treatment arms was not deemed to be possible or useful. What was attempted was an analysis of change from baseline values for the ACTOplus met® XR arm.
The plan was to summarize for baseline, post-exposure, and absolute change by treatment arm using the appropriate descriptive statistics, and will be evaluated with Student's t-test or Wilcoxon rank-sum test.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=37769 genes
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=37769 genes
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Genes With Significant Changes From Baseline to Days 11-22 for Tumor-Normal Tissue: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000232479
|
1.0013 raw counts of RNA sequencing reads
Standard Deviation 0.0072
|
-1.0087 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
|
Genes With Significant Changes From Baseline to Days 11-22 for Tumor-Normal Tissue: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000233163
|
1.0037 raw counts of RNA sequencing reads
Standard Deviation 0.0193
|
-1.0003 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
|
Genes With Significant Changes From Baseline to Days 11-22 for Tumor-Normal Tissue: Change in Whole Transcriptome Gene Analysis on Total Ribonucleic Acid Samples
ENSG00000249245
|
-1.0098 raw counts of RNA sequencing reads
Standard Deviation 0.0050
|
0.0000 raw counts of RNA sequencing reads
Standard Deviation NA
only 1 data point
|
SECONDARY outcome
Timeframe: BaselineHuman papillomavirus status will be assessed in tumor tissue by p16 by immunohistochemistry.
Outcome measures
| Measure |
Group I (ACTOplus Met XR)
n=4 Participants
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 Participants
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Human Papillomavirus Status Assessed in Tumor Tissue by p16 by Immunohistochemistry
Positive
|
2 Participants
|
0 Participants
|
|
Human Papillomavirus Status Assessed in Tumor Tissue by p16 by Immunohistochemistry
Not Tested
|
2 Participants
|
2 Participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: Baseline to days 11-22Population: No one consented to this aspect of the study, no data is available.
Tumor fluorodeoxyglucose uptake/metabolism assess by treatment positron emission tomography/computed tomography.
Outcome measures
Outcome data not reported
Adverse Events
Group I (ACTOplus Met XR)
Serious events: 0 serious events
Other events: 4 other events
Deaths: 0 deaths
Group II (Placebo)
Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
| Measure |
Group I (ACTOplus Met XR)
n=4 participants at risk
Patients receive ACTOplus met XR PO QD for 10-21 days in the absence of disease progression or unacceptable toxicity. Patients may continue ACTOplus met XR PO QD for a maximum of 25 days if end of treatment biopsy/surgical treatment is delayed beyond day 22.
Laboratory Biomarker Analysis: Correlative studies
Metformide Hydrochloride/Pioglitazone Hydrochloride Extended-Release Tablet: Given PO
Pharmacological Study: Correlative studies
|
Group II (Placebo)
n=2 participants at risk
Patients receive placebo PO QD daily for 10-21 days.
Laboratory Biomarker Analysis: Correlative studies
Pharmacological Study: Correlative studies
Placebo: Given PO
|
|---|---|---|
|
Vascular disorders
Hypertension
|
25.0%
1/4 • Number of events 1 • up to 22 days
|
50.0%
1/2 • Number of events 1 • up to 22 days
|
|
Gastrointestinal disorders
Abdominal Pain
|
25.0%
1/4 • Number of events 1 • up to 22 days
|
0.00%
0/2 • up to 22 days
|
|
Respiratory, thoracic and mediastinal disorders
Allergic Rhinitis
|
25.0%
1/4 • Number of events 1 • up to 22 days
|
0.00%
0/2 • up to 22 days
|
|
Gastrointestinal disorders
Diarrhea
|
25.0%
1/4 • Number of events 2 • up to 22 days
|
0.00%
0/2 • up to 22 days
|
|
Gastrointestinal disorders
Nausea
|
25.0%
1/4 • Number of events 2 • up to 22 days
|
0.00%
0/2 • up to 22 days
|
|
Respiratory, thoracic and mediastinal disorders
Sore Throat
|
25.0%
1/4 • Number of events 1 • up to 22 days
|
0.00%
0/2 • up to 22 days
|
|
Nervous system disorders
Dizziness
|
0.00%
0/4 • up to 22 days
|
50.0%
1/2 • Number of events 1 • up to 22 days
|
|
General disorders
Fatigue
|
25.0%
1/4 • Number of events 1 • up to 22 days
|
0.00%
0/2 • up to 22 days
|
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place
Restriction type: LTE60