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Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer

This study is currently recruiting participants.
Verified July 2017 by Case Comprehensive Cancer Center
Sponsor:
ClinicalTrials.gov Identifier:
NCT01666730
First Posted: August 16, 2012
Last Update Posted: July 19, 2017
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
  Purpose
This phase II trial studies how well metformin hydrochloride, leucovorin calcium, fluorouracil, and oxaliplatin work in treating patients with metastatic pancreatic cancer. Metformin hydrochloride may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as leucovorin calcium, fluorouracil, and oxaliplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving metformin hydrochloride together with combination chemotherapy may kill more tumor cells

Condition Intervention Phase
Acinar Cell Adenocarcinoma of the Pancreas Duct Cell Adenocarcinoma of the Pancreas Recurrent Pancreatic Cancer Stage IV Pancreatic Cancer Drug: metformin hydrochloride Drug: oxaliplatin Drug: leucovorin calcium Drug: fluorouracil Other: laboratory biomarker analysis Phase 2

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase II Study of Metformin Plus Modified FOLFOX 6 in Patients With Metastatic Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Case Comprehensive Cancer Center:

Primary Outcome Measures:
  • Median overall survival (OS) [ Time Frame: Time from first day of treatment to death from any cause, assessed up to 1 year ]
    Calculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.


Secondary Outcome Measures:
  • Response Rate (RR) objective tumor response based on computed tomography (CT) scans or magnetic resonance imaging (MRI) scans according to Response Evaluation Criteria in Solid Tumors (RECIST) [ Time Frame: 1 year ]
    The overall response is the number of participants who experience a confirmed complete (CR) or partial response (PR) of the total analysis population. Per the Response Evaluation Criteria In Solid Tumors (RECIST): CR = all detectable tumor has disappeared, PR = a >=30% decrease in the sum of the longest dimensions of the target lesions taking as a reference the baseline sum, Progressive disease (PD) = a >=20% increase in target lesions, Stable Disease = small changes that do not meet previously given criteria. The true response rate of the combination therapy for this patient population will be estimated based on the number of response using a binomial distribution and its confidence intervals will be estimated using Wilson's method.

  • Progression free survival according to RECIST 1.1 Criteria [ Time Frame: Time from first day of treatment received to the earlier documented disease progression or death from any cause, assessed up to 1 year ]
    Calculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.

  • Number of grade 3 and 4 toxicities according to NCI CTCAE version 4.0 [ Time Frame: Up to 1 year ]
    The toxicity profile of the combination will be tabulated.


Estimated Enrollment: 43
Actual Study Start Date: February 15, 2013
Estimated Study Completion Date: March 2018
Estimated Primary Completion Date: October 2017 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Treatment (metformin hydrochloride, FOLFOX)
Patients receive metformin hydrochloride PO BID on days 1-14 and FOLFOX therapy comprising leucovorin calcium IV over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity.
Drug: metformin hydrochloride
Given PO
Other Name: Glucophage
Drug: oxaliplatin
Given IV
Other Names:
  • 1-OHP
  • Dacotin
  • Dacplat
  • Eloxatin
  • L-OHP
Drug: leucovorin calcium
Given IV
Other Names:
  • CF
  • CFR
  • LV
Drug: fluorouracil
Given IV
Other Names:
  • 5-fluorouracil
  • 5-Fluracil
  • 5-FU
Other: laboratory biomarker analysis
Correlative studies

Detailed Description:

PRIMARY OBJECTIVES:

I. To determine if metformin (metformin hydrochloride) when added to FOLFOX ( leucovorin calcium, fluorouracil, oxaliplatin) improves overall survival in patients with metastatic pancreatic cancer.

SECONDARY OBJECTIVES:

I. To assess response rate (RR). II. To assess progression free survival (PFS). III. To assess toxicity in patients with metastatic pancreatic cancer receiving FOLFOX and metformin. IV. To identify tumor/serum correlative markers.

OUTLINE: Patients receive metformin hydrochloride orally (PO) twice daily (BID) on days 1-7 for an introductory period before the addition of FOLFOX. After the introductory period, patients will continue metformin twice daily and FOLFOX therapy comprising leucovorin calcium intravenously (IV) over 120 minutes, fluorouracil IV continuously over 46 hours, and oxaliplatin IV over 120 minutes on day 1. Courses repeat every 14 days in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients are followed up for periodically.

  Eligibility

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Patients must have histologically or cytologically confirmed metastatic pancreatic adenocarcinoma (or any mixed pathology if adenocarcinoma is predominant)
  • Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded) as > 20 mm with conventional techniques or as > 10 mm with spiral computed tomography (CT) scan
  • Patient must have not received systemic chemotherapy for metastatic disease; prior chemotherapy, radiation therapy, concurrent chemoradiation are allowed if used for treatment of non-metastatic disease; prior palliative radiation for symptom management is allowed; any chemotherapy must have been completed 4 weeks prior to enrollment; any radiotherapy must have been completed 2 weeks prior to enrollment
  • Eastern Cooperative Oncology Group (ECOG) performance status 0-2
  • Absolute neutrophil count ≥ 1,500/L
  • Platelets ≥ 100,000/L
  • Hemoglobin ≥ 9 g/dL
  • Total bilirubin ≤ 2 mg/dL
  • Aspartate aminotransferase (AST) (serum glutamic oxaloacetic transaminase [SGOT]/alanine aminotransferase (ALT) (serum glutamic pyruvate transaminase [SGPT]) ≤ 2.5 x institutional upper limit of normal
  • Creatinine ≤ 1.5
  • Women of childbearing potential and men must agree to use adequate contraception (double 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 that she is pregnant while she or her partner is participating in this study, she should inform the treating physician immediately
  • Subjects must have the ability to understand and the willingness to sign a written informed consent document
  • Patients with diabetes 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)

Exclusion Criteria:

  • Chemotherapy within 4 weeks prior to entering the study, radiotherapy within 2 weeks prior to entering the study or failure to recover from adverse events due to agents administered more than 4 weeks earlier
  • Prior treatment toxicities must be resolved to ≤ grade 1 according to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 4.0
  • Current use of metformin for more than 6 months prior to enrollment on study
  • Use of any other investigational agents
  • Patients with untreated brain metastases should be excluded from this clinical trial
  • History of allergic reactions attributed to compounds of similar chemical or biological composition to metformin or oxaliplatin or fluorouracil (5-FU)
  • Active second primary malignancy or history of second primary malignancy within the last 3 years, with the exception of basal cell skin cancers or carcinoma in situ that have been adequately treated
  • 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
  • Pregnant or nursing women
  • Human immunodeficiency virus (HIV)-positive patients
  • Chronic or planned acute alcohol use of three or more drinks per day
  • Metabolic acidosis, acute or chronic, including ketoacidosis
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01666730


Locations
United States, Ohio
University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Smitha S. Krishnamurthi    216-844-5467    smitha.krishnamurthi@uhhospitals.org   
Principal Investigator: Smitha S. Krishnamurthi         
Cleveland Clinic Taussig Cancer Institute, Case Comprehensive Cancer Center Active, not recruiting
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Comprehensive Cancer Center
National Cancer Institute (NCI)
Investigators
Principal Investigator: Smitha Krishnamurthi, MD University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01666730     History of Changes
Other Study ID Numbers: CASE1212
NCI-2012-01322 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
First Submitted: August 14, 2012
First Posted: August 16, 2012
Last Update Posted: July 19, 2017
Last Verified: July 2017

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: No

Additional relevant MeSH terms:
Adenocarcinoma
Pancreatic Neoplasms
Carcinoma, Acinar Cell
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Metformin
Oxaliplatin
Fluorouracil
Levoleucovorin
Leucovorin
Hypoglycemic Agents
Physiological Effects of Drugs
Antineoplastic Agents
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Antidotes
Protective Agents
Vitamin B Complex
Vitamins