Metformin Plus Modified FOLFOX 6 in Metastatic Pancreatic Cancer

NCT01666730 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: CASE1212
• Study Type: interventional
• Target: 50
• Locations: 1 country
• Sites: 2

Brief Summary

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

Conditions

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage IV Pancreatic Cancer

Outcome Measures

Primary Outcomes (1)

• Median Overall Survival (OS)

  Calculated using Kaplan Meier methods and the median will be estimated assuming an exponential distribution.

  Time from first day of treatment to death from any cause, assessed up to 1 year

Secondary Outcomes (4)

• 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)

  1 year

• Clinical Benefit Rate (CBR) Based on Computed Tomography (CT) Scans or Magnetic Resonance Imaging (MRI) Scans According to RECIST

  1 year

• Progression Free Survival According to RECIST 1.1 Criteria

  Time from first day of treatment received to the earlier documented disease progression or death from any cause, assessed up to 1 year

• Number of Grade 3 and 4 Toxicities According to NCI CTCAE Version 4.0

  Up to 1 year

Study Arms (1)

Treatment (metformin hydrochloride, FOLFOX)

EXPERIMENTAL

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; Drug: oxaliplatin; Drug: leucovorin calcium; Drug: fluorouracil; Other: laboratory biomarker analysis

Interventions

metformin hydrochloride DRUG

Given PO

Also known as: Glucophage

Treatment (metformin hydrochloride, FOLFOX)

oxaliplatin DRUG

Given IV

Also known as: 1-OHP, Dacotin, Dacplat, Eloxatin, L-OHP

Treatment (metformin hydrochloride, FOLFOX)

leucovorin calcium DRUG

Given IV

Also known as: CF, CFR, LV

Treatment (metformin hydrochloride, FOLFOX)

fluorouracil DRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU

Treatment (metformin hydrochloride, FOLFOX)

laboratory biomarker analysis OTHER

Correlative studies

Treatment (metformin hydrochloride, FOLFOX)

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead

Study Sites (2)

University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106, United States

Location

Cleveland Clinic Taussig Cancer institute, Case Comprehensive Cancer Center

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Metformin; Oxaliplatin; Leucovorin; Fluorouracil

Condition Hierarchy (Ancestors)

Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Endocrine Gland Neoplasms; Digestive System Diseases; Pancreatic Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Coordination Complexes; Formyltetrahydrofolates; Tetrahydrofolates; Folic Acid; Pterins; Pteridines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Coenzymes; Enzymes and Coenzymes; Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring

Results Point of Contact

• Title: Dr. David Bajor
• Organization: University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

CTUReferral@UHhospitals.org

1-800-641-2422

Study Officials

• David Bajor, MD

  University Hospitals Cleveland Medical Center, Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 14, 2012
• First Posted: August 16, 2012
• Study Start: February 21, 2013
• Primary Completion: August 1, 2018
• Study Completion: August 1, 2018
• Last Updated: August 10, 2021
• Results First Posted: August 10, 2021

Record last verified: 2021-07

Locations

US (2)