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A Study of Metformin With or Without Rapamycin as Maintenance Therapy After Induction Chemotherapy in Subjects With Pancreatic Cancer

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. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02048384
Recruitment Status : Completed
First Posted : January 29, 2014
Last Update Posted : April 12, 2021
Sponsor:
Collaborator:
Stand Up To Cancer
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Tracking Information
First Submitted Date  ICMJE January 23, 2014
First Posted Date  ICMJE January 29, 2014
Last Update Posted Date April 12, 2021
Actual Study Start Date  ICMJE June 10, 2014
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: May 11, 2017)
safety and feasibility [ Time Frame: 1 year ]
To determine the safety and feasibility of administering metformin with or without rapamycin in subjects with metastatic pancreatic ductal adenocarcinoma (PDA) after disease stabilization on chemotherapy.
Original Primary Outcome Measures  ICMJE
 (submitted: January 27, 2014)
safety and feasibility [ Time Frame: 1 year ]
To determine the safety and feasibility of administering metformin with or without rapamycin in subjects with metastatic pancreatic ductal adenocarcinoma (PDA) after disease stabilization on chemotherapy. This is an exploratory study designed to assess the safety and feasibility of the use of maintenance therapy in the first line treatment of subjects with metastatic pancreatic cancer. The study will be continuously monitoring for adverse events in each arm. If the unacceptable toxicity events appear to be higher than 30%, we will temporarily halt the study pending dose modification. Specifically, we will apply Bayesian toxicity monitoring. In determining feasibility of enrolling patients onto a maintenance study, if less than 6 patients are enrolled in the first 12 months investigators will re-evaluate the strategy. Feasibility will also be assessed by the ability for the study to complete enrollment within 24 months after the first subject is enrolled.
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures
 (submitted: May 11, 2017)
  • FDG uptake [ Time Frame: 1 year ]
    To evaluate fludeoxyglucose (FDG) uptake in metastatic PDA subjects treated with metformin with or without rapamycin.
  • mTOR activity [ Time Frame: 1 year ]
    To measure mammalian target of rapamycin (mTOR) activity in peripheral blood mononuclear cells (PBMC) of subjects treated with metformin with or without rapamycin.
  • estimation of RR, TTP, PFS, OS [ Time Frame: 1 year ]
    To estimate response rate (RR), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in subjects with metastatic PDA treated with metformin with or without rapamycin.
  • CA19-9 measurement [ Time Frame: 1 year ]
    To measure tumor marker kinetics (CA 19-9) in subjects treated with metformin with or without rapamycin.
Original Other Pre-specified Outcome Measures
 (submitted: January 27, 2014)
  • FDG uptake [ Time Frame: 1 year ]
    To evaluate fludeoxyglucose (FDG) uptake in metastatic PDA subjects treated with metformin with or without rapamycin.
  • H1F1 & glutaminate expression [ Time Frame: 1 year ]
    To measure HIF1 and glutaminate expression in tumors of subjects treated with metformin with or without rapamycin.
  • histological evaluation [ Time Frame: 1 year ]
    To evaluate extracellular matrix by histology in tumors of subjects treated with metformin with or without rapamycin.
  • mTOR activity [ Time Frame: 1 year ]
    To measure mammalian target of rapamycin (mTOR) activity in peripheral blood mononuclear cells (PBMC) of subjects treated with metformin with or without rapamycin.
  • estimation of RR, TTP, PFS, OS [ Time Frame: 1 year ]
    To estimate response rate (RR), time to progression (TTP), progression-free survival (PFS) and overall survival (OS) in subjects with metastatic PDA treated with metformin with or without rapamycin.
  • CA19-9 measurement [ Time Frame: 1 year ]
    To measure tumor marker kinetics (CA 19-9) in subjects treated with metformin with or without rapamycin.
 
Descriptive Information
Brief Title  ICMJE A Study of Metformin With or Without Rapamycin as Maintenance Therapy After Induction Chemotherapy in Subjects With Pancreatic Cancer
Official Title  ICMJE An Exploratory Study of Metformin With or Without Rapamycin as Maintenance Therapy After Induction Chemotherapy in Subjects With Metastatic Pancreatic Adenocarcinoma
Brief Summary This is a phase 1b, multi-center, open label, randomized study to evaluate the safety and feasibility of administering metformin with or without rapamycin after disease stabilization on chemotherapy in subjects with metastatic PDA.
Detailed Description

Subjects with metastatic PDA who have received FOLFIRINOX or a gemcitabine-containing regimen and have achieved stable disease or better will be enrolled onto this study. Subjects should have had at least 6 months of chemotherapy and decline continuation of chemotherapy and should have stable disease or better on 2 scans taken at least 6 weeks apart. If applicable, subjects should also have a stable or declining CA19-9.

Twenty-two subjects will be randomized in a 1:1 ratio to metformin (Arm A) or metformin + rapamycin (Arm B). Subjects will be stratified according to their prior chemotherapy regimen: FOLFIRINOX or a gemcitabine-containing regimen.

Treatments will be administered orally on a 28 day cycle. Metformin will be administered 850mg twice daily and rapamycin will be administered 4mg daily.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Metastatic Pancreatic Adenocarcinoma
Intervention  ICMJE
  • Drug: metformin alone (Arm A)
    metformin alone
    Other Name: Glumetza, Fortamet, Riomet, Glucophage
  • Drug: metformin (Arm B)
    rapamycin + metformin
    Other Name: Glumetza, Fortamet, Riomet, Glucophage
  • Drug: rapamycin (Arm B)
    rapamycin + metformin
    Other Name: Sirolimus, Rapamune
Study Arms  ICMJE
  • Experimental: A - metformin alone
    metformin alone Arm A patients will receive metformin 850mg orally twice a day on a 28 day cycle.
    Intervention: Drug: metformin alone (Arm A)
  • Active Comparator: B - metformin + rapamycin
    metformin + rapamycin Arm B patients will receive 850mg orally twice a day and rapamycin 4mg orally once a day on a 28 day cycle.
    Interventions:
    • Drug: metformin (Arm B)
    • Drug: rapamycin (Arm B)
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 27, 2014)
22
Original Estimated Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE September 2019
Actual Primary Completion Date February 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Histologically or cytologically confirmed metastatic pancreatic adenocarcinoma. Subjects with islet cell neoplasms are excluded.
  • Have received 6 months of chemotherapy.
  • Have stable disease for at least 6 months on the current regimen with the last 2 scans taken at least 6 months apart. Measurable disease not required.
  • Eastern Cooperative Oncology Group performance status 0 or 1.
  • Life expectancy of greater than 12 weeks.
  • Adequate organ and marrow function.
  • Oxygen saturation on room air > 92 % by pulse oximetry. (Subjects on intermittent or continuous supplemental oxygen are excluded).
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) prior to study entry and for the duration of study participation.
  • Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

  • Receiving or has received any other investigational agents within 28 days prior to Day 1 of treatment in this study.
  • Has undergone major surgery, other than diagnostic surgery (i.e. surgery done to obtain a biopsy for diagnosis or an aborted Whipple), within 28 days prior to Day 1 of treatment in this study.
  • Known history of brain metastases unless previously treated and well controlled for at least 3 months (defined as stable clinically, no edema, no steroids).
  • History of allergic reactions attributed to compounds of similar chemical or biologic composition to metformin or rapamycin.
  • Taking ketoconazole, voriconazole, itraconazole, erythromycin, telithromycin, clarithromycin, rifampin, rifabutin, bromocriptine, cimetidine, cisapride, clotrimazole, danazol, diltiazem, fluconazole, protease inhibitors (e.g., HIV and hepatitis C that include drugs such as ritonavir, indinavir, boceprevir, and telaprevir), metoclopramide, nicardipine, troleandomycin, verapamil, carbamazepine, phenobarbital, phenytoin, rifapentine, St. John's Wort (Hypericum perforatum), and grapefruit juice. Subjects on metformin will not be excluded.
  • Has received any non-oncology live vaccine therapy used for prevention of infectious diseases for up to 28 days prior to or after the initiation of treatment in this study.
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection (bacterial, viral, or fungal infection(s) requiring systemic therapy), symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements.
  • Has serious medical risk factors involving any of the major organ systems such that the Investigator considers it unsafe for the subject to receive an experimental research drug.
  • Unhealed surgical wound or other clinically significant wound.
  • Known history of chronic HIV, Hepatitis B or hepatitis C infections.
  • Pregnant or breast feeding.
  • Unwilling or unable to comply with study procedures.
  • Cannot reliably swallow pills.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT02048384
Other Study ID Numbers  ICMJE J13146
NA_00090282 ( Other Identifier: JHMIRB )
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Study Sponsor  ICMJE Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Collaborators  ICMJE Stand Up To Cancer
Investigators  ICMJE
Study Chair: Dung Le, MD Johns Hopkins SKCCC
PRS Account Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Verification Date April 2021

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP