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Metformin and Nightly Fasting in Women With Early Breast Cancer

Primary Purpose

Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ

Status
Recruiting
Phase
Phase 2
Locations
International
Study Type
Interventional
Intervention
Biospecimen Collection
Extended Release Metformin Hydrochloride
Monitoring
Nutritional Assessment
Short-Term Fasting
Sponsored by
M.D. Anderson Cancer Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional prevention trial for Anatomic Stage I Breast Cancer AJCC v8

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

Inclusion Criteria:

  • Women with histologically confirmed luminal (ER+ve and/or progesterone [PgR]+ve >= 1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve (cT1, cN0) IBC and DCIS are also eligible
  • Age >= 18 years
  • Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%)
  • Leukocytes >= 3,000/microliter
  • Absolute neutrophil count >= 1,500/microliter
  • Platelets >= 100,000/microliter
  • Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal
  • Creatinine within normal institutional limits
  • Creatinine clearance estimated with Cockcroft-Gault formula > 45 mL/min
  • Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of metformin hydrochloride extended release on the developing human fetus at the recommended therapeutic dose are unknown
  • Ability to understand and the willingness to sign a written informed consent document

Exclusion Criteria:

  • Body mass index (BMI) < 18.5 Kg/m^2
  • Previous treatment for breast cancer including chemotherapy and endocrine therapy
  • Women who are planned to receive neoadjuvant therapy (HER2+ve T2 or N+ve IBC or women < 50 years with luminal B IBC)
  • Triple negative breast cancer (BC)
  • Documented history of symptomatic hypoglycemia
  • Diabetic patients or participants with fasting glucose level >= 126 mg/dL
  • Known hypersensitivity or intolerance to metformin hydrochloride extended release
  • Participants should not be receiving any other investigational agents
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
  • History of lactic acidosis
  • Liver dysfunction including chronic active hepatitis and cirrhosis not compensated
  • History of vitamin B12 deficiency or megaloblastic anemia
  • Chronic use of large doses of diuretics (e.g., > 80 mg furosemide)
  • Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and intrauterine devices (IUDs)
  • Concomitant use of topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide)
  • Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between metformin hydrochloride extended release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin hydrochloride extended release was used during pregnancy, these studies cannot definitely establish the absence of any metformin hydrochloride extended release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin hydrochloride extended release, breastfeeding should be discontinued if the mother is treated with metformin hydrochloride extended release. Moreover, prolonged fasting is not recommended in pregnant woman
  • Women who practice any type of intermittent fasting program
  • Women who will not have anyone available to assist them in case of need

Sites / Locations

  • M D Anderson Cancer CenterRecruiting
  • Galliera HospitalRecruiting
  • European Institute of Oncology

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Active Comparator

Arm Label

Arm I (fasting, glucose monitoring, counseling, metformin)

Arm II (glucose monitoring)

Arm Description

Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release PO QD until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).

Outcomes

Primary Outcome Measures

Frequency of occurrence of dose limiting toxicity
Defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug.
Change in pre-post treatment Ki67 labeling index in invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) (in the absence of IBC)
Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as body mass index [BMI] and HER2 status).
Difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or intraepithelial neoplasia Ki67 between arms
Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as BMI and HER2 status).

Secondary Outcome Measures

Change in circulating biomarkers
Will include Homeostatic model assessment index, highly sensitive C-reactive protein, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, leptin and adiponectin. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. Analysis of covariance (ANCOVA) models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.
Change of CIP2A-PP2A-GSK3beta-MCL-1 axis in cancer tissue
Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.
Change of Ki67 in cancer tissue
Will depend upon next generation sequencing mutational profile obtained in post-treatment surgical specimens. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.
Difference of M30
Will be assessed between arms. Will be assessed using IHC.
Difference of phosphorylated S6
Will be assessed between arms. Will be assessed using IHC.
Physiological distress
Will be correlated with response biomarkers.
Eating habits
Will be correlated with response biomarkers.
Tobacco
Will be correlated with response biomarkers.
Alcohol consumption
Will be correlated with response biomarkers.
Incidence of adverse events
Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0.
Difference of the area under the curve of glucose levels
Will be assessed between arms.

Full Information

First Posted
August 26, 2021
Last Updated
June 21, 2023
Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)
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1. Study Identification

Unique Protocol Identification Number
NCT05023967
Brief Title
Metformin and Nightly Fasting in Women With Early Breast Cancer
Official Title
Time Restricted Eating And Metformin (TEAM) in Invasive Breast Cancer (IBC) or Ductal Carcinoma in Situ (DCIS). A Randomized, Phase IIb, Window of Opportunity Presurgical Trial.
Study Type
Interventional

2. Study Status

Record Verification Date
June 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 4, 2023 (Actual)
Primary Completion Date
November 20, 2025 (Anticipated)
Study Completion Date
November 20, 2025 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
M.D. Anderson Cancer Center
Collaborators
National Cancer Institute (NCI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product
Yes
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
This phase IIb trial studies the combined effect of prolonged nightly fasting and metformin hydrochloride extended release in decreasing breast tumor cell proliferation and other biomarkers of breast cancer. Preventing invasive breast cancer or DCIS. Metformin is widely used to treat type II diabetes and is associated with a decreased risk of cancer and death in diabetic individuals. Intermittent fasting may protect cancer patients from the toxic effects of chemotherapy agents without causing chronic weight loss. The combination of intermittent fasting and metformin may reduce breast cancer growth and may be used in women at risk for breast cancer or other cancers associated with being overweight.
Detailed Description
PRIMARY OBJECTIVES: I. To assess the safety of the experimental intervention based on the frequency of occurrence of a dose limiting toxicity (DLT) in the first 14 participants assigned to the experimental treatment arm. II. Evaluate the difference in post-treatment Ki67 labeling index (LI) in cancer adjacent ductal carcinoma in situ (DCIS) (in the presence of invasive breast cancer [IBC]), if present, or intraepithelial neoplasia (IEN) (defined as atypical ductal hyperplasia [ADH] or atypical lobular hyperplasia [ALH] or lobular carcinoma in situ [LCIS]) between the active treatment and the control group. SECONDARY OBJECTIVES: I. To explore the effect of intervention on the change of expression of PP2A-GSK3beta-MCL-1 axis in pre-post treatment cancer tissue levels. II. To measure the change in circulating biomarkers: Homeostatic model assessment (HOMA) index, highly sensitive C-reactive protein (CRP) (hsCRP), C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, adipokines (leptin and adiponectin). III. To correlate a customized next generation sequencing (NGS) mutational profile panel focused on estrogen receptor (ER) positive (+ve) with the response of Ki67. IV. To measure the difference of cell death by immunohistochemistry (IHC) for M30 in post- treatment cancer samples between arms. V. To measure the difference of phosphorylated (p)S6 by IHC in post- treatment cancer samples between arms. VI. To assess safety and toxicities according to National Cancer Institute (NCI)-Common Terminology Criteria for Adverse Events (CTCAE) version (v.) 5.0. VII. To correlate physiological distress, eating habits, tobacco and alcohol consumption with the response of Ki67 between arms. VIII. To compare the area under the curve (AUC) of glucose levels between arms and within the experimental arm according to different doses of metformin hydrochloride extended release (0 mg, 750 mg and 1500 mg). OUTLINE: Patients are randomized to 1 of 2 arms. ARM I: Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release orally (PO) once daily (QD) until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). ARM II: Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43). After completion of study intervention, patients are followed up at 30 days.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Anatomic Stage I Breast Cancer AJCC v8, Anatomic Stage II Breast Cancer AJCC v8, Breast Ductal Carcinoma In Situ, Invasive Breast Carcinoma

7. Study Design

Primary Purpose
Prevention
Study Phase
Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Randomized
Enrollment
120 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Arm I (fasting, glucose monitoring, counseling, metformin)
Arm Type
Experimental
Arm Description
Patients fast for >= 16 hours every night and use the continuous glucose monitoring system for 4-6 weeks. Patients also receive nutritional counseling sessions on days 0 and 10. Beginning week 2, patients also receive metformin hydrochloride extended release PO QD until the day of surgery. Treatment continues for 4-6 weeks (until surgery) in the absence of disease progression or unacceptable toxicity. Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).
Arm Title
Arm II (glucose monitoring)
Arm Type
Active Comparator
Arm Description
Patients continue their usual dietary pattern and use the continuous glucose monitoring system for 4-6 weeks (until surgery). Patients undergo the collection of blood samples at baseline and at the final study visit (days 28-43), and the collection of tissue at the time of surgery (days 28-43).
Intervention Type
Procedure
Intervention Name(s)
Biospecimen Collection
Other Intervention Name(s)
Biological Sample Collection, Biospecimen Collected, Specimen Collection
Intervention Description
Undergo collection of blood and tissue samples
Intervention Type
Drug
Intervention Name(s)
Extended Release Metformin Hydrochloride
Other Intervention Name(s)
ER Metformin Hydrochloride, Extended-release Metformin Hydrochloride, Glucophage XR, Glumetza, Metformin Hydrochloride Extended Release
Intervention Description
Given PO
Intervention Type
Other
Intervention Name(s)
Monitoring
Other Intervention Name(s)
monitor
Intervention Description
Use continuous glucose monitoring system
Intervention Type
Other
Intervention Name(s)
Nutritional Assessment
Other Intervention Name(s)
Dietary Assessment, dietary counseling, nutritional counseling
Intervention Description
Receive nutritional counseling
Intervention Type
Other
Intervention Name(s)
Short-Term Fasting
Other Intervention Name(s)
Intermittent Fasting, Short-term Intermittent Fasting
Intervention Description
Perform intermittent fasting
Primary Outcome Measure Information:
Title
Frequency of occurrence of dose limiting toxicity
Description
Defined as a hypoglycemic event requiring permanent discontinuation of study treatment or any grade 3 or greater adverse event possibly, probably, or definitely related to the study drug.
Time Frame
Up to 4-6 weeks
Title
Change in pre-post treatment Ki67 labeling index in invasive breast cancer (IBC) or ductal carcinoma in situ (DCIS) (in the absence of IBC)
Description
Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as body mass index [BMI] and HER2 status).
Time Frame
Baseline up to 4-6 weeks
Title
Difference in post-treatment adjacent DCIS (in the presence of IBC), if present, or intraepithelial neoplasia Ki67 between arms
Description
Generalized linear models will be used to assess differences between treatment arms for Ki67. Log transformation will be considered to obtain normal distribution of residuals. Will also evaluate the need to adjust for baseline characteristics and significant confounders (such as BMI and HER2 status).
Time Frame
Post-treatment (4-6 weeks)
Secondary Outcome Measure Information:
Title
Change in circulating biomarkers
Description
Will include Homeostatic model assessment index, highly sensitive C-reactive protein, C-peptide, IGF-I, IGFBP-1, IGFBP-3, free IGF-I, Hb1Ac, lipid profile, leptin and adiponectin. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. Analysis of covariance (ANCOVA) models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.
Time Frame
Baseline up to 4-6 weeks
Title
Change of CIP2A-PP2A-GSK3beta-MCL-1 axis in cancer tissue
Description
Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.
Time Frame
Baseline up to 4-6 weeks
Title
Change of Ki67 in cancer tissue
Description
Will depend upon next generation sequencing mutational profile obtained in post-treatment surgical specimens. Will present full distributions and median values of circulating biomarkers, Ki67, at baseline, after treatment, and of changes and percentage changes (with interquartile ranges) of all continuous variables, by arms. ANCOVA models will evaluate the associations of post values (after treatment) and changes from baseline by study arms adjusting for baseline values, explanatory variables and possible confounders (such as age and BMI). Normal distribution of residuals from full models will be checked and, if needed, a transformation will be considered.
Time Frame
Baseline up to 4-6 weeks
Title
Difference of M30
Description
Will be assessed between arms. Will be assessed using IHC.
Time Frame
Post-treatment
Title
Difference of phosphorylated S6
Description
Will be assessed between arms. Will be assessed using IHC.
Time Frame
Post-treatment
Title
Physiological distress
Description
Will be correlated with response biomarkers.
Time Frame
Up to 4-6 weeks
Title
Eating habits
Description
Will be correlated with response biomarkers.
Time Frame
Up to 4-6 weeks
Title
Tobacco
Description
Will be correlated with response biomarkers.
Time Frame
Up to 4-6 weeks
Title
Alcohol consumption
Description
Will be correlated with response biomarkers.
Time Frame
Up to 4-6 weeks
Title
Incidence of adverse events
Description
Evaluated according to the Common Terminology Criteria for Adverse Events version 5.0.
Time Frame
Up to 4-6 weeks
Title
Difference of the area under the curve of glucose levels
Description
Will be assessed between arms.
Time Frame
Up to 4-6 weeks

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Women with histologically confirmed luminal (ER+ve and/or progesterone [PgR]+ve >= 1%) operable IBC (cT1-2, cN0-1, Mx) candidate to elective surgery and not to neo-adjuvant treatment. Women with larger tumors who refuse neo-adjuvant chemotherapy before surgery can also be eligible. Luminal HER2+ve (cT1, cN0) IBC and DCIS are also eligible Age >= 18 years Eastern Cooperative Oncology Group (ECOG) performance status =< 1 (Karnofsky >= 70%) Leukocytes >= 3,000/microliter Absolute neutrophil count >= 1,500/microliter Platelets >= 100,000/microliter Aspartate aminotransferase (AST) (serum glutamic-oxaloacetic transaminase [SGOT])/alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 1.5 x institutional upper limit of normal Creatinine within normal institutional limits Creatinine clearance estimated with Cockcroft-Gault formula > 45 mL/min Female participants of child-bearing potential must agree to use contraception such as barrier method of birth control or abstinence, prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she has to inform her study physician immediately. The effects of metformin hydrochloride extended release on the developing human fetus at the recommended therapeutic dose are unknown Ability to understand and the willingness to sign a written informed consent document Exclusion Criteria: Body mass index (BMI) < 18.5 Kg/m^2 Previous treatment for breast cancer including chemotherapy and endocrine therapy Women who are planned to receive neoadjuvant therapy (HER2+ve T2 or N+ve IBC or women < 50 years with luminal B IBC) Triple negative breast cancer (BC) Documented history of symptomatic hypoglycemia Diabetic patients or participants with fasting glucose level >= 126 mg/dL Known hypersensitivity or intolerance to metformin hydrochloride extended release Participants should not be receiving any other investigational agents Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements History of lactic acidosis Liver dysfunction including chronic active hepatitis and cirrhosis not compensated History of vitamin B12 deficiency or megaloblastic anemia Chronic use of large doses of diuretics (e.g., > 80 mg furosemide) Current use of oral hormonal contraceptives or female hormones in the last four weeks or 5 half-lives, excluding vaginal creams and intrauterine devices (IUDs) Concomitant use of topiramate or other carbonic anhydrase inhibitors (e.g., zonisamide, acetazolamide or dichlorphenamide) Pregnant women are excluded from this study because even though published data from post-marketing studies have not reported a clear association between metformin hydrochloride extended release and major birth defects, miscarriage, or adverse maternal or fetal outcomes when metformin hydrochloride extended release was used during pregnancy, these studies cannot definitely establish the absence of any metformin hydrochloride extended release associated risk because of methodological limitations, including small sample size and inconsistent comparator groups. Because there is an unknown but potential risk for adverse events (AEs) in nursing infants secondary to treatment of the mother with metformin hydrochloride extended release, breastfeeding should be discontinued if the mother is treated with metformin hydrochloride extended release. Moreover, prolonged fasting is not recommended in pregnant woman Women who practice any type of intermittent fasting program Women who will not have anyone available to assist them in case of need
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Andrea De Censi
Organizational Affiliation
M.D. Anderson Cancer Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
M D Anderson Cancer Center
City
Houston
State/Province
Texas
ZIP/Postal Code
77030
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Parijatham Thomas, MD
Phone
713-745-1075
Email
psthomas@mdanderson.org
First Name & Middle Initial & Last Name & Degree
Parijatham Thomas, MD
Facility Name
Galliera Hospital
City
Genoa
ZIP/Postal Code
16128
Country
Italy
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Andrea De Censi
Phone
39-0105634501
Email
andrea.decensi@galliera.it
First Name & Middle Initial & Last Name & Degree
Andrea De Censi
Facility Name
European Institute of Oncology
City
Milano
ZIP/Postal Code
20141
Country
Italy
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Bernardo Bonanni
Phone
39-0257489022
Email
bernardo.bonanni@ieo.it
First Name & Middle Initial & Last Name & Degree
Bernardo Bonanni

12. IPD Sharing Statement

Plan to Share IPD
Yes
IPD Sharing Plan Description
NCI is committed to sharing data in accordance with NIH policy. For more details on how clinical trial data is shared, access the link to the NIH data sharing policy page.
IPD Sharing URL
https://grants.nih.gov/policy/sharing.htm

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Metformin and Nightly Fasting in Women With Early Breast Cancer

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