Stage IA Pancreatic AdenocarcinomaPhase 2NCT02005419
Metformin Combined With Gemcitabine as Adjuvant Therapy for Pancreatic Cancer After Curative Resection
A Phase 2 study testing Gemcitabine and Metformin in people with Stage IA Pancreatic Adenocarcinoma and Stage IB Pancreatic Adenocarcinoma, run by Xian-Jun Yu at 1 site in China.
Trial summary
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Stage IA Pancreatic Adenocarcinoma, Stage IB Pancreatic Adenocarcinoma, Stage IIA Pancreatic Adenocarcinoma
- What is being tested?
- Gemcitabine and Metformin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 300 participants
- Where
- 1 siteChina
- Study dates
- Dec 2013to Dec 2017
- Phase
- Phase 2
- 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 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Signed informed content obtained prior to treatment
- Age ≥ 18 years and ≤ 80 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patients must have histologically confirmed pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant) after curative resection (R0). The pathological staging does not exceed the stage IIB.
- No tumor lesions are seen by abdominal and thoracic CT scan 4~8 weeks after surgery, and no serious adverse events are occurred during this period
- The expected survival after surgery ≥ 6 months
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- White blood cell (WBC) ≥ 3 × 10^9/L; Absolute neutrophil count (ANC) ≥ 1.5 × 10^9/L; Platelets (PLT) ≥ 100 × 10^9/L; Hemoglobin (Hgb) ≥ 9 g/dL
- Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/ alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 × institutional upper limit of normal (ULN); Total bilirubin (TBIL) ≤ ULN; Creatinine (CRE) ≤ 1.5 × ULN
- Prothrombin time (PT) and international normalized ratio (INR) ≤ 1.5 × ULN
- Patients with diabetes (diagnosed after surgery) are eligible for this trial; all diabetic patients who are enrolled on this study should discuss the need to change their diabetes management regimen with their primary care physician or endocrinologist prior to enrollment
- Diabetic patients who are on metformin are eligible as long as they have been on metformin for less than 6 months (estimated 6 months or less duration of metformin therapy from start of metformin to enrollment on study)
Who cannot join
- Active second primary malignancy or history of second primary malignancy within the last 3 years
- Patients who have received any form of anti-tumor therapy before surgery, including chemotherapy, radiotherapy, interventional chemoembolization, radiofrequency ablation, and molecular targeted therapy
- Use of any other investigational agents
- Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of allergic reactions attributed to compounds of similar chemical or biological composition to metformin or gemcitabine
- Current use of metformin for more than 6 months prior to enrollment on study
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- Metabolic acidosis, acute or chronic, including ketoacidosis
- Pregnant or nursing women
- Human immunodeficiency virus (HIV)-positive patients
- Patients who are unwilling or unable to comply with study procedures
Trial locations and contacts
1 site in 1 country.
China1 site
Department of Pancreatic and Hepatobiliary Surgery, Fudan University Shanghai Cancer Center; Pancreatic Cancer Institute, Fudan University
Shanghai, 200032
About this study
Official title: A Phase II, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of the Combination of Gemcitabine and Metformin in Treating Patients With Pancreatic Cancer After Curative Resection
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. Data from clinical trials indicate that adjuvant chemotherapy enhances 5-year survival to ~25% for patients who have undergone surgery to remove their tumor; and gemcitabine is the standard regimen of chemotherapy. Metformin is the first-line treatment for type 2 diabetes mellitus. Literatures reported that metformin might inhibit tumor growth by blocking some enzymes needed for cell growth. Some retrospective studies have revealed that diabetic patients taking metformin were less likely to develop pancreatic cancer. Additionally, pancreatic cancer patients treated with metformin showed a better survival than those without metformin. In this study, the researchers intend to investigate the activity and safety of the combination of gemcitabine and metformin in treating patients with pancreatic cancer that have removed by surgery.
- Conditions
- Stage IA Pancreatic Adenocarcinoma, Stage IB Pancreatic Adenocarcinoma, Stage IIA Pancreatic Adenocarcinoma, Stage IIB Pancreatic Adenocarcinoma
- Being tested
- Gemcitabine, Metformin, placebo
- Keywords
- Pancreatic Cancer, Pancreatic Adenocarcinoma, Metformin, Gemcitabine, Adjuvant Therapy
- Medical subject headings
- Pancreatic Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
GemcitabineDrug
Also called GEMZAR
Patients receive gemcitabine 1000 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment, and also receive placebo (Arm I)/ metformin (Arm II) on days 1-28. Treatment repeats every 4 weeks for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.
MetforminDrug
Also called glucophage
Metformin will be administered at a dose of 500 mg twice daily. If well tolerated, the dose will be increased to 1000 mg twice daily in the second week. Treatment repeats every 4 weeks (2 g on days 1-28) for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.
placeboDrug
Placebo will be administered at a dose of 500 mg twice daily. If well tolerated, the dose will be increased to 1000 mg twice daily in the second week. Treatment repeats every 4 weeks (2 g on days 1-28) for up to 6 circles in the absence of disease recurrence or unacceptable toxicity.
| Study group | Role | What they receive |
|---|---|---|
| gemcitabine + placebo | Placebo comparator | gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; placebo at 2 g on days 1-28 Receives: Drug: Gemcitabine; Drug: placebo |
| gemcitabine + metformin | Experimental | gemcitabine at 1000 mg/m^2 on days 1, 8, and 15; metformin at 2 g on days 1-28 Receives: Drug: Gemcitabine; Drug: Metformin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recurrence-free survival at one year after curative resection
To evaluate the therapeutic efficacy of gemcitabine chemotherapy with versus without metformin hydrochloride in terms of recurrence-free survival in patients with pancreatic cancer at one year after curative resection. Computed tomography (CT) scan
Measured: From date of randomization (after curative resection) until the date of first documented recurrence or date of death from any cause, whichever came first, assessed 2 months during therapy and 3 months thereafter up to 24 months
Secondary outcomes (3)
Overall survival after curative resection
To evaluate the overall survival of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Measured: From date of randomization (after curative resection) until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months
Quality of life score after curative resection
To evaluate the quality of life score of patients (after curative resection) treated with this regimen. Outpatient visit, phone interview
Measured: One month during therapy and 3 months thereafter up to 24 months
Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0
To evaluate the occurrence of grade 3 and 4 toxicities according to National Cancer Institute Common Toxicity Criteria for Adverse Events (NCI CTCAE; version 4.0) in patients treated with this regimen. The toxicity profile includes but not limits neutropenia, thrombocytopenia, peripheral neuropathy, hypoglycemia, metabolic acidosis (acute or chronic, including ketoacidosis), which will be summarized as the percentage of patients by type and grade according to treatment group. Outpatient visit, laboratory findings
Measured: One week during therapy and 3 months thereafter up to 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Dec 2013 (estimated)
- Study startDec 2013
- Primary completionFeb 2017
- Study completionDec 2017
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Stage IA Pancreatic AdenocarcinomaStudies of the same condition, open and under way.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 300 participants (actual)
Sponsor and investigators
- Lead sponsor
- Xian-Jun Yu
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Xian-Jun Yu, Fudan University
- Investigators
- Xianjun Yu, M.D., Ph.D., Principal investigator, Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Shanghai Pancreatic Cancer Institute; Pancreatic Cancer Institute, Fudan University. Shanghai, China.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02005419
- Sponsor's protocol ID
- MET1310128-2
- Status last verified
- Feb 2019
- First submitted
- 24 Nov 2013
- Last updated
- 5 Feb 2019
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II, Randomized, Double-blind, Placebo Controlled Study to Evaluate the Efficacy and Safety of the Combination of Gemcitabine and Metformin in Treating Patients With Pancreatic Cancer After Curative Resection
- ClinicalTrials.gov ID
- NCT02005419
- Acronym / sponsor ID
- MET1310128-2
- Conditions
- Stage IA Pancreatic Adenocarcinoma, Stage IB Pancreatic Adenocarcinoma, Stage IIA Pancreatic Adenocarcinoma, Stage IIB Pancreatic Adenocarcinoma
- Keywords
- Pancreatic Cancer, Pancreatic Adenocarcinoma, Metformin, Gemcitabine, Adjuvant Therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 300 participants (actual)
- Lead sponsor
- Xian-Jun YuUniversity, hospital or other
- Study start
- Dec 2013 (actual)
- Primary completion
- Feb 2017 (actual)
- Study completion
- Dec 2017 (actual)
- First posted
- 9 Dec 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.
Pancreatic cancer represents the most lethal of the common malignancies with a 5-year survival rate of less than 5%. For patients who are eligible for potentially curative resection, despite mortality and morbidity rates after surgery have improved, the recurrence rate is up to 85% within 2 years. Data from clinical trials indicate that adjuvant chemotherapy enhances 5-year survival to ~25% for patients who have undergone surgery to remove their tumor; and gemcitabine is the standard regimen of chemotherapy. Metformin is the first-line treatment for type 2 diabetes mellitus. Literatures reported that metformin might inhibit tumor growth by blocking some enzymes needed for cell growth. Some retrospective studies have revealed that diabetic patients taking metformin were less likely to develop pancreatic cancer. Additionally, pancreatic cancer patients treated with metformin showed a better survival than those without metformin. In this study, the researchers intend to investigate the activity and safety of the combination of gemcitabine and metformin in treating patients with pancreatic cancer that have removed by surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| gemcitabine + placebo | Placebo comparator | Drug: Gemcitabine, Drug: placebogemcitabine at 1000 mg/m^2 on days 1, 8, and 15; placebo at 2 g on days 1-28 |
| gemcitabine + metformin | Experimental | Drug: Gemcitabine, Drug: Metformingemcitabine at 1000 mg/m^2 on days 1, 8, and 15; metformin at 2 g on days 1-28 |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Signed informed content obtained prior to treatment
- Age ≥ 18 years and ≤ 80 years
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Patients must have histologically confirmed pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant) after curative resection (R0). The pathological staging does not exceed the stage IIB.
- No tumor lesions are seen by abdominal and thoracic CT scan 4~8 weeks after surgery, and no serious adverse events are occurred during this period
Key exclusion criteria (10 listed)
- Active second primary malignancy or history of second primary malignancy within the last 3 years
- Patients who have received any form of anti-tumor therapy before surgery, including chemotherapy, radiotherapy, interventional chemoembolization, radiofrequency ablation, and molecular targeted therapy
- Use of any other investigational agents
- Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, internal hemorrhage, pancreatic leakage, bile leakage, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- History of allergic reactions attributed to compounds of similar chemical or biological composition to metformin or gemcitabine
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 |
|---|---|---|
| GemcitabineAlso: GEMZARPatients receive gemcitabine 1000 mg/m^2 (iv, 30 minutes) on days 1, 8, and 15 for 3 weeks, followed by one week without treatment, and also receive placebo (Arm I)/ metformin (Arm II) on days 1-28. Treatment repeats every 4 weeks for up to 6 circles in the absence of disease recurrence or unacceptable toxicity. | Drug | gemcitabine + metformin, gemcitabine + placebo |
| MetforminAlso: glucophageMetformin will be administered at a dose of 500 mg twice daily. If well tolerated, the dose will be increased to 1000 mg twice daily in the second week. Treatment repeats every 4 weeks (2 g on days 1-28) for up to 6 circles in the absence of disease recurrence or unacceptable toxicity. | Drug | gemcitabine + metformin |
| placeboPlacebo will be administered at a dose of 500 mg twice daily. If well tolerated, the dose will be increased to 1000 mg twice daily in the second week. Treatment repeats every 4 weeks (2 g on days 1-28) for up to 6 circles in the absence of disease recurrence or unacceptable toxicity. | Drug | gemcitabine + placebo |
Primary outcome
Recurrence-free survival at one year after curative resection
Time frame: From date of randomization (after curative resection) until the date of first documented recurrence or date of death from any cause, whichever came first, assessed 2 months during therapy and 3 months thereafter up to 24 months
To evaluate the therapeutic efficacy of gemcitabine chemotherapy with versus without metformin hydrochloride in terms of recurrence-free survival in patients with pancreatic cancer at one year after curative resection. Computed tomography (CT) scan
3 secondary outcomes
Overall survival after curative resection
Time frame: From date of randomization (after curative resection) until the date of death from any cause, assessed one month during therapy and 3 months thereafter up to 24 months
Quality of life score after curative resection
Time frame: One month during therapy and 3 months thereafter up to 24 months
Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0
Time frame: One week during therapy and 3 months thereafter up to 24 months
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2019.
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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.
Xianjun Yu, M.D., Ph.D. principal investigator
Department of Pancreatic Surgery, Fudan University Shanghai Cancer Center; Shanghai Pancreatic Cancer Institute; Pancreatic Cancer Institute, Fudan University. Shanghai, China.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Gemcitabine and Metformin in people with Stage IA Pancreatic Adenocarcinoma and Stage IB Pancreatic Adenocarcinoma, run by Xian-Jun Yu at 1 site in China.
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 10 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: finished, as of the sponsor's last update on 5 Feb 2019. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Recurrence-free survival at one year after curative resection (time frame: From date of randomization (after curative resection) until the date of first documented recurrence or date of death from any cause, whichever came first, assessed 2 months during therapy and 3 months thereafter up to 24 months). 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 5 Feb 2019.