Stereotactic Radiosurgery and Metformin in Patients With Borderline-Resectable or Locally-Advanced Pancreatic Cancer

NCT02153450 | Completed Early Phase 1 FDA Drug

• 4 other identifiers: CASE4213NCI-2014-01172CASE 4213P30CA043703
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

This pilot clinical trial studies stereotactic radiosurgery and metformin hydrochloride in treating patients with pancreatic cancer that may be removed (borderline-resectable) or not removed by surgery. Stereotactic radiosurgery may be able to send x-rays directly to the tumor and cause less damage to normal tissue. Metformin hydrochloride, used for diabetes, may also kill cancer cells as demonstrated in laboratory studies. Giving stereotactic radiosurgery with metformin hydrochloride may kill more tumor cells.

Conditions

Acinar Cell Adenocarcinoma of the Pancreas; Duct Cell Adenocarcinoma of the Pancreas; Recurrent Pancreatic Cancer; Stage I-III Pancreatic Cancer

Keywords

pancreatic cancer; Radiation; Metformin; Pancreatic Adenocarcinomas

Outcome Measures

Primary Outcomes (1)

• Dose-limiting toxicity (DLT) rate scored according to the National Cancer Institute Common Toxicity Criteria version 4

  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 Outcomes (3)

• Clinical response rate using the revised Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1

  Up to 2 years

• Progression-free survival using the revised RECIST version 1.1

  Time from start of treatment to time of progression or death, whichever occurs first, assessed up to 2 years

• Overall survival

  Up to 2 years

Study Arms (1)

Treatment (stereotactic radiosurgery, metformin hydrochloride)

EXPERIMENTAL

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.

Drug: metformin hydrochloride; Radiation: stereotactic radiosurgery

Interventions

metformin hydrochloride DRUG

Given PO

Also known as: Glucophage

Treatment (stereotactic radiosurgery, metformin hydrochloride)

stereotactic radiosurgery RADIATION

Undergo stereotactic radiosurgery

Treatment (stereotactic radiosurgery, metformin hydrochloride)

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Case Comprehensive Cancer Center: lead
• National Cancer Institute (NCI): collaborator

Study Sites (1)

University Hospitals Cleveland Medical Center, Seidman Cancer Center, Case Comprehensive Cancer Center

Cleveland, Ohio, 44106-5065, United States

Location

MeSH Terms

Conditions

Pancreatic Neoplasms

Interventions

Metformin; Radiosurgery

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; Radiotherapy; Therapeutics; Stereotaxic Techniques; Neurosurgical Procedures; Surgical Procedures, Operative; Investigative Techniques

Study Officials

• Jennifer Dorth

  Case Comprehensive Cancer Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 30, 2014
• First Posted: June 3, 2014
• Study Start: May 8, 2015
• Primary Completion: August 3, 2018
• Study Completion: June 13, 2020
• Last Updated: June 26, 2020

Record last verified: 2020-06

Locations

US (1)