Stage IA Pancreatic CancerPhase 1NCT01954732
Metformin Hydrochloride in Treating Patients With Pancreatic Cancer That Can be Removed by Surgery
A Phase 1 study testing metformin hydrochloride and pharmacological study in people with Stage IA Pancreatic Cancer and Stage IB Pancreatic Cancer, run by Case Comprehensive Cancer Center.
Trial summary
This randomized clinical trial studies metformin hydrochloride in treating patients with pancreatic cancer that can be removed by surgery. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer
- What is being tested?
- metformin hydrochloride and pharmacological study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 0 participants
- Where
- No sites listed yet
- Study dates
- Jan 2014to Mar 2015
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients must have histologically or cytologically confirmed resectable pancreatic carcinoma; patients with pancreatic neuroendocrine tumors are not eligible
- Patients must be previously untreated with chemotherapy or radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients must have surgical resection of the pancreas planned, with enrollment at least 7 days prior to surgery; patients with surgery scheduled > 15 days will not be excluded
- Hemoglobin (Hg)A1C must be below 7%
- Total bilirubin less than 1.5 X institutional upper limit of normal
Show all 11Show fewer
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]) =< 2.5 X institutional upper limit of normal
- Alanine aminotransferase (ALT) (serum glutamate pyruvate transaminase [SGPT]) =< 2.5 X institutional upper limit of normal
- Serum creatinine within normal institutional limits
- Alkaline phosphatase < 1.5 X institutional upper limit of normal
- Subjects must have the ability to understand and be willing to provide written informed consent
Who cannot join
- History of metformin use in the previous 3 months
- Treatment with neoadjuvant chemotherapy or radiation therapy
- History of allergic reactions attributed to metformin
- Patients with 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
- Metabolic acidosis, acute or chronic, including ketoacidosis
- Metastatic disease
About this study
Official title: A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer
This randomized clinical trial studies metformin hydrochloride in treating patients with pancreatic cancer that can be removed by surgery. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the effect of escalating doses of metformin (metformin hydrochloride) given pre-operatively on pancreatic cancer cell proliferation and apoptosis.
SECONDARY OBJECTIVES:
- To assess toxicity of escalating doses of metformin given pre-operatively in patients with resectable pancreatic carcinoma.
II. To measure the effect of metformin on the expression of phosphorylated acetyl-CoA carboxylase alpha (ACC), phosphorylated mechanistic target of rapamycin (serine/threonine kinase) (mTOR), and pancreatic cancer stem cells.
OUTLINE: Patients are randomized to 1 of 3 treatment groups.
GROUP I: Patients undergo observation.
GROUP II: Patients receive metformin hydrochloride orally (PO) twice daily (BID) for at least 7 days in the absence of disease progression or unacceptable toxicity.
GROUP III: Patients receive metformin hydrochloride as in Group II.
After completion of study treatment, patients are followed up 30 days.
- Conditions
- Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer
- Being tested
- metformin hydrochloride, pharmacological study
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
metformin hydrochlorideDrug
Also called Glucophage
Given PO
Also called pharmacological studies
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Group I (observation) | No intervention | Patients undergo observation. |
| Group II (metformin hydrochloride) | Experimental | Patients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: metformin hydrochloride; Other: pharmacological study |
| Group III (metformin hydrochloride) | Experimental | Patients receive metformin hydrochloride as in Group II. Receives: Drug: metformin hydrochloride; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Pancreatic tumor cell proliferation and apoptosis as measured by the percentage of cells Ki-67+, percentage of cells TUNEL+, and mitotic counts in tissue samples
The difference between treatment groups will be compared using analysis of variance (ANOVA) (3 groups) followed by Tukey's pair-wise comparison procedure. Transformation may be applied (e.g. natural log) prior to analysis to better approximate normality.
Measured: At time of surgery (after 7 days of treatment)
Secondary outcomes (3)
Occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0)
Will be summarized as the percentage of patients by type and grade according to treatment group.
Measured: Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first
Expression of pACC and pMTOR quantified by the mean fluorescence intensity (MFI) in tissue samples
The difference between treatment groups will be compared using ANOVA followed by Tukey's pair-wise comparison procedure. Laser scanning cytometry and iCyte software used to quantify the MFI of pACC and pMTOR.
Measured: At time of surgery (after 7 days of treatment)
Percentage of pancreatic cancer stem cells in tissue samples
For each of biologic biomarkers (pACC, pMTOR, CD44+CD24+ESA+ cells), the difference between treatment groups will be compared using ANOVA (3 groups) followed by Tukey's pair-wise comparison procedure. Transformation may be applied (e.g. natural log) prior to analysis to better approximate normality.
Measured: At time of surgery (after 7 days of treatment)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted7 Oct 2013 (estimated)
- Study startJan 2014
- Primary completionMar 2015
- Study completionMar 2015
Why it stopped: Slow accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IA Pancreatic CancerStudies of the same condition, open and under way.
- More trials run by Case Comprehensive Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 0 participants (actual)
Sponsor and investigators
- Lead sponsor
- Case Comprehensive Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jennifer Eads, MD, Principal investigator, Case Comprehensive Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01954732
- Sponsor's protocol ID
- CASE1213
- Other IDs
- NCI-2013-01836, CASE 1213, P30CA043703
- Status last verified
- Jul 2015
- First submitted
- 27 Sep 2013
- Last updated
- 15 Jul 2015
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 15 Jul 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Pharmacodynamic Study of Metformin in Patients With Resectable Pancreatic Cancer
- ClinicalTrials.gov ID
- NCT01954732
- Acronym / sponsor ID
- CASE1213
- Conditions
- Stage IA Pancreatic Cancer, Stage IB Pancreatic Cancer, Stage IIA Pancreatic Cancer, Stage IIB Pancreatic Cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- WithdrawnReason stopped: Slow accrual
- Enrolment
- 0 participants (actual)
- Lead sponsor
- Case Comprehensive Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Jan 2014
- Primary completion
- Mar 2015 (actual)
- Study completion
- Mar 2015 (actual)
- First posted
- 7 Oct 2013 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This randomized clinical trial studies metformin hydrochloride in treating patients with pancreatic cancer that can be removed by surgery. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth.
Detailed description
PRIMARY OBJECTIVES:
- To determine the effect of escalating doses of metformin (metformin hydrochloride) given pre-operatively on pancreatic cancer cell proliferation and apoptosis.
SECONDARY OBJECTIVES:
- To assess toxicity of escalating doses of metformin given pre-operatively in patients with resectable pancreatic carcinoma.
II. To measure the effect of metformin on the expression of phosphorylated acetyl-CoA carboxylase alpha (ACC), phosphorylated mechanistic target of rapamycin (serine/threonine kinase) (mTOR), and pancreatic cancer stem cells.
OUTLINE: Patients are randomized to 1 of 3 treatment groups.
GROUP I: Patients undergo observation.
GROUP II: Patients receive metformin hydrochloride orally (PO) twice daily (BID) for at least 7 days in the absence of disease progression or unacceptable toxicity.
GROUP III: Patients receive metformin hydrochloride as in Group II.
After completion of study treatment, patients are followed up 30 days.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group I (observation) | No intervention | –Patients undergo observation. |
| Group II (metformin hydrochloride) | Experimental | Drug: metformin hydrochloride, Other: pharmacological studyPatients receive metformin hydrochloride PO BID for at least 7 days in the absence of disease progression or unacceptable toxicity. |
| Group III (metformin hydrochloride) | Experimental | Drug: metformin hydrochloride, Other: pharmacological studyPatients receive metformin hydrochloride as in Group II. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Patients must have histologically or cytologically confirmed resectable pancreatic carcinoma; patients with pancreatic neuroendocrine tumors are not eligible
- Patients must be previously untreated with chemotherapy or radiation therapy
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2
- Patients must have surgical resection of the pancreas planned, with enrollment at least 7 days prior to surgery; patients with surgery scheduled > 15 days will not be excluded
- Hemoglobin (Hg)A1C must be below 7%
Key exclusion criteria (6 listed)
- History of metformin use in the previous 3 months
- Treatment with neoadjuvant chemotherapy or radiation therapy
- History of allergic reactions attributed to metformin
- Patients with 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
- Metabolic acidosis, acute or chronic, including ketoacidosis
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| metformin hydrochlorideAlso: GlucophageGiven PO | Drug | Group II (metformin hydrochloride), Group III (metformin hydrochloride) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Group II (metformin hydrochloride), Group III (metformin hydrochloride) |
Primary outcome
Pancreatic tumor cell proliferation and apoptosis as measured by the percentage of cells Ki-67+, percentage of cells TUNEL+, and mitotic counts in tissue samples
Time frame: At time of surgery (after 7 days of treatment)
The difference between treatment groups will be compared using analysis of variance (ANOVA) (3 groups) followed by Tukey's pair-wise comparison procedure. Transformation may be applied (e.g. natural log) prior to analysis to better approximate normality.
3 secondary outcomes
Occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0)
Time frame: Baseline to 30 days after treatment has been discontinued or after the date of surgery, whichever occurs first
Expression of pACC and pMTOR quantified by the mean fluorescence intensity (MFI) in tissue samples
Time frame: At time of surgery (after 7 days of treatment)
Percentage of pancreatic cancer stem cells in tissue samples
Time frame: At time of surgery (after 7 days of treatment)
Results and safety
The study was withdrawn before enrolling participants, so there are no results.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Jul 2015.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jennifer Eads, MD principal investigator
Case Comprehensive Cancer Center
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing metformin hydrochloride and pharmacological study in people with Stage IA Pancreatic Cancer and Stage IB Pancreatic Cancer, run by Case Comprehensive Cancer Center.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: withdrawn, as of the sponsor's last update on 15 Jul 2015. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was withdrawn before enrolling participants, so there are no results.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Pancreatic tumor cell proliferation and apoptosis as measured by the percentage of cells Ki-67+, percentage of cells TUNEL+, and mitotic counts in tissue samples (time frame: At time of surgery (after 7 days of treatment)). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 15 Jul 2015.