- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02153450
Stereotactic Radiosurgery and Metformin in Patients With Borderline-Resectable or Locally-Advanced Pancreatic Cancer
A Pilot Trial of Stereotactic Body Radiation Therapy and Metformin for Borderline-Resectable and Locally-Advanced Pancreatic Adenocarcinomas
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
This is an open label pilot, single-center, non-randomized trial is designed to evaluate the tolerability and preliminary activity of the combination of stereotactic body radiation therapy (SBRT) with metformin for resectable and locally-advanced pancreatic/periampullary cancers.
PRIMARY OBJECTIVES:
The primary objectives of this study are to:
1) To determine if the addition of metformin to SBRT adds minimal additional toxicity for patients with A). borderline-resectable or B). not surgically resectable pancreatic adenocarcinomas.
SECONDARY OBJECTIVES:
I. Evaluate the clinical/pathological response and resectability rates associated with these regimens.
OUTLINE:
Patients receive metformin hydrochloride orally (PO) daily or twice daily (BID) on days -11 to -1. Patients then undergo stereotactic radiosurgery 5 days a week for 5 weeks and receive concurrent metformin hydrochloride* by mouth, two times a day for 5 weeks. Patients undergo laparotomy on week 6 (or weeks 5-7). ). Systemic therapy continues as soon as it is considered feasible by the treating physicians.
*NOTE: Metformin hydrochloride should be stopped 2 days before laparotomy.
After completion of study treatment, patients are followed up every 3 months for 2 years.
Study Type
Enrollment (Actual)
Phase
- Early Phase 1
Contacts and Locations
Study Locations
-
-
Ohio
-
Cleveland, Ohio, United States, 44106-5065
- University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Subjects must be able to provide written informed consent
- Histologically and/or cytologically confirmed adenocarcinoma of the pancreas, clinical stage T1-4, N0-1, M0
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Hemoglobin ≥ 9.0 g/dl
- Alkaline phosphatase < 3 x upper limit of normal (ULN)
- Albumin > 2.5 g/dL
- Absolute neutrophil count ≥ 1500/mm^3
- Platelet count ≥ 75,000/mm^3
- Total bilirubin < 1.5 x upper limit of normal (ULN)
- 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
- Creatinine ≤ 1.5
Borderline-resectable or locally-advanced pancreatic cancer (based upon impression of the surgical oncologist, in conjunction with radiologic consultations) as defined per the Alliance consensus :
Borderline-resectable
- An interface between the primary tumor and superior mesenteric vein (SMV)/portal vein measuring 180 degrees or greater of the circumference of the vein wall
- Short-segment occlusion of the SMV/portal vein but with suitable vessel proximal and distal to the obstruction to allow safe resection and reconstruction
- Short-segment interface (of any degree) between the tumor and the hepatic artery with normal artery proximal and distal to the interface that is amenable to resection and arterial reconstruction
- An interface between the tumor and the SMA or celiac trunk measuring less than 180 degrees of the circumference of the artery wall
Not surgically resectable due to one or more of the following things
- Patient is not a surgical candidate due to medical comorbidities and/or poor performance status
- Patient elects not to undergo surgical therapy
Patient has locally-advanced pancreatic cancer based on having one of the following:
- Encasement of the SMA/celiac artery (>180 degrees).
- Involvement of the SMV/portal vein without options for reconstruction.
- Aortic invasion or encasement.
- Women of child-bearing potential and men must agree to use adequate contraception (double barrier method of birth control or abstinence) 6 weeks prior to study entry, for the duration of study participation and for 6 months after completing treatment; 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
- Patients previously treated with chemotherapy are eligible unless they have evidence of local or distant disease progression; patients must have completed their last cycle of chemotherapy at least two weeks prior to study enrollment
- Patients currently taking metformin are eligible for participation.
- Women of child-bearing potential and male patients who are sexually-active must agree to use effective methods of birth control throughout protocol treatment.
- Patients must not have poorly-controlled diarrhea (no more than 4 loose stools per day). Patients may be reconsidered for the study if the diarrhea resolves.
Exclusion Criteria:
- Evidence of gross duodenal invasion, gastric outlet obstruction
- Gastrointestinal perforation or intra-abdominal abscess (< 3 months); recent (< 3 months) gastrointestinal (GI) bleeding from gastric or duodenal ulcer
- Systemic collagen vascular disease including scleroderma or systemic lupus erythematosus (SLE); rheumatoid arthritis is eligible
- Serious active infection requiring intravenous (IV) antibiotics
- Conditions leading to inadequate gastrointestinal tract absorption as determined by the treating physician and/or investigator
- Patients with uncontrolled intercurrent illness including, but not limited to ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Poorly-controlled diarrhea (> 4 loose bowel movement [BM]/day without use of anti-motility agents) within 7 days of study enrollment; patients may be reconsidered for the study if the diarrhea resolves
- Comorbid conditions that, in the opinion of the investigator, would complicate safety or compliance such as known human immunodeficiency virus (HIV) or current substance abuse
- Patients who are pregnant or lactating
- Patients who are unwilling or unable to comply with study and/or follow-up procedures
- Treatment for other carcinomas within the last two years, except cured non-melanoma skin cancer, curatively treated in-situ cervical cancer, or localized prostate cancer with stable prostate-specific antigen (PSA)
- Multi-focal pancreatic lesions concerning for cancer.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Treatment (stereotactic radiosurgery, metformin hydrochloride)
Patients receive metformin hydrochloride PO daily or BID on days -11 to -1. Patients then undergo stereotactic radiosurgery 5 days a week for 5 weeks and receive concurrent metformin hydrochloride* PO BID for 5 weeks. Patients undergo laparotomy on week 6 (or weeks 5-7). Systemic therapy continues as soon as it is considered feasible by the treating physicians. *NOTE: Metformin hydrochloride should be stopped 2 days before laparotomy. |
Given PO
Other Names:
Undergo stereotactic radiosurgery
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Dose-limiting toxicity (DLT) rate scored according to the National Cancer Institute Common Toxicity Criteria version 4
Time Frame: Up to 21 days post-treatment
|
The rate of DLT for each treatment group will be estimated based on the number of incidences using a binomial distribution and its confidence intervals will be estimated using Wilson's method.
The factors associated with DLT will be identified using logistic regression using forward model selection procedure
|
Up to 21 days post-treatment
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Clinical response rate using the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1
Time Frame: Up to 2 years
|
Using a binomial distribution and its confidence intervals will be estimated using Wilson's method.
|
Up to 2 years
|
Progression-free survival using the revised RECIST version 1.1
Time Frame: Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
|
The factors associated with progression-free survival will be identified using logistic regression using forward model selection procedure.
|
Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years
|
Overall survival
Time Frame: Up to 2 years
|
The probability of overall survival along with median survival for each treatment group will be estimated using Kaplan-Meier method.
|
Up to 2 years
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Jennifer Dorth, Case Comprehensive Cancer Center
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Digestive System Diseases
- Neoplasms by Histologic Type
- Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Endocrine System Diseases
- Digestive System Neoplasms
- Endocrine Gland Neoplasms
- Pancreatic Diseases
- Adenocarcinoma
- Pancreatic Neoplasms
- Carcinoma, Acinar Cell
- Hypoglycemic Agents
- Physiological Effects of Drugs
- Metformin
Other Study ID Numbers
- CASE4213
- P30CA043703 (U.S. NIH Grant/Contract)
- NCI-2014-01172 (Registry Identifier: CTRP (Clinical Trial Reporting Program))
- CASE 4213 (Other Identifier: Case Comprehensive Cancer Center)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Acinar Cell Adenocarcinoma of the Pancreas
-
Mohammed Najeeb Al HallakNational Cancer Institute (NCI)CompletedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Stage IV Pancreatic CancerUnited States
-
National Cancer Institute (NCI)TerminatedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Stage IV Pancreatic CancerUnited States
-
Fox Chase Cancer CenterNational Cancer Institute (NCI)TerminatedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Stage III Pancreatic Cancer | Stage IIB Pancreatic CancerUnited States
-
John DeWittAmerican Society for Gastrointestinal Endoscopy; Pinnacle Biologics Inc.CompletedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Stage III Pancreatic CancerUnited States
-
National Cancer Institute (NCI)CompletedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Recurrent Pancreatic Cancer | Stage IV Pancreatic CancerUnited States
-
Case Comprehensive Cancer CenterCompletedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Recurrent Pancreatic Cancer | Stage IV Pancreatic CancerUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Recurrent Pancreatic Cancer | Stage IV Pancreatic CancerUnited States
-
Yale UniversityNational Cancer Institute (NCI)Active, not recruitingAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Stage IIA Pancreatic Cancer | Stage IIB Pancreatic Cancer | Stage I Pancreatic CancerUnited States
-
Alliance for Clinical Trials in OncologyNational Cancer Institute (NCI)CompletedAcinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Recurrent Pancreatic Cancer | Stage III Pancreatic Cancer | Stage II Pancreatic CancerUnited States
-
Mayo ClinicCompletedUnspecified Adult Solid Tumor, Protocol Specific | Acinar Cell Adenocarcinoma of the Pancreas | Duct Cell Adenocarcinoma of the Pancreas | Recurrent Pancreatic Cancer | Stage IV Pancreatic CancerUnited States
Clinical Trials on metformin hydrochloride
-
Haisco Pharmaceutical Group Co., Ltd.The Fourth Hospital of Hebei Medical UniversityRecruitingDiabetic Neuropathies | Diabetic Neuropathy PeripheralChina
-
University of UtahNational Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)Recruiting
-
University of ArizonaNational Cancer Institute (NCI)RecruitingOral Leukoplakia | ErythroplakiaUnited States, Canada
-
National Cancer Institute (NCI)RecruitingLung CarcinomaUnited States, Canada
-
GlaxoSmithKlineCompleted
-
UConn HealthCompletedAging | Vaccine Response Impaired | Age-Related ImmunodeficiencyUnited States
-
Johns Hopkins UniversityBaylor College of Medicine; National Heart, Lung, and Blood Institute (NHLBI); Temple UniversityNot yet recruitingAsthma | Overweight and Obesity | Asthma Chronic
-
RenJi HospitalCompleted
-
Laboratorios Silanes S.A. de C.V.Completed
-
Bing HeActive, not recruitingPolycystic Ovary SyndromeChina