Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified January 2014 by Case Comprehensive Cancer Center
Sponsor:
Collaborator:
Information provided by (Responsible Party):
Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier:
NCT01666730
First received: August 14, 2012
Last updated: May 6, 2014
Last verified: January 2014
  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: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: Yes ]
    The toxicity profile of the combination will be tabulated.


Estimated Enrollment: 43
Study Start Date: February 2013
Estimated Study Completion Date: September 2014
Estimated Primary Completion Date: September 2014 (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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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 alcohol use or a history of alcohol abuse (defined as ingestion of >= 3 drinks per day)
  • Metabolic acidosis, acute or chronic, including ketoacidosis
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01666730

Locations
United States, Ohio
Case Medical Center, University Hospitals 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
Investigators
Principal Investigator: Smitha Krishnamurthi, MD Case Medical Center, University Hospitals Seidman Cancer Center, Case Comprehensive Cancer Center
  More Information

No publications provided

Responsible Party: Case Comprehensive Cancer Center
ClinicalTrials.gov Identifier: NCT01666730     History of Changes
Other Study ID Numbers: CASE1212, NCI-2012-01322
Study First Received: August 14, 2012
Last Updated: May 6, 2014
Health Authority: United States: Food and Drug Administration

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
Fluorouracil
Oxaliplatin
Leucovorin
Levoleucovorin
Metformin
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Antimetabolites, Antineoplastic
Antineoplastic Agents
Therapeutic Uses
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Vitamin B Complex
Vitamins
Micronutrients

ClinicalTrials.gov processed this record on July 23, 2014