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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 : Active, not recruiting
First Posted : January 29, 2014
Last Update Posted : January 10, 2019
Sponsor:
Collaborator:
Stand Up To Cancer
Information provided by (Responsible Party):
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

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.

Condition or disease Intervention/treatment Phase
Metastatic Pancreatic Adenocarcinoma Drug: metformin alone (Arm A) Drug: metformin (Arm B) Drug: rapamycin (Arm B) Phase 1 Phase 2

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.


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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 22 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: An Exploratory Study of Metformin With or Without Rapamycin as Maintenance Therapy After Induction Chemotherapy in Subjects With Metastatic Pancreatic Adenocarcinoma
Study Start Date : January 2014
Estimated Primary Completion Date : December 2019
Estimated Study Completion Date : December 2020


Arm Intervention/treatment
Experimental: A - metformin alone
metformin alone Arm A patients will receive metformin 850mg orally twice a day on a 28 day cycle.
Drug: metformin alone (Arm A)
metformin alone
Other Name: Glumetza, Fortamet, Riomet, Glucophage

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.
Drug: metformin (Arm B)
rapamycin + metformin
Other Name: Glumetza, Fortamet, Riomet, Glucophage

Drug: rapamycin (Arm B)
rapamycin + metformin
Other Name: Sirolimus, Rapamune




Primary Outcome Measures :
  1. 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.


Other Outcome Measures:
  1. FDG uptake [ Time Frame: 1 year ]
    To evaluate fludeoxyglucose (FDG) uptake in metastatic PDA subjects treated with metformin with or without rapamycin.

  2. 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.

  3. 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.

  4. CA19-9 measurement [ Time Frame: 1 year ]
    To measure tumor marker kinetics (CA 19-9) in subjects treated with metformin with or without rapamycin.



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02048384


Locations
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United States, Arizona
Scottsdale Healthcare Hospitals DBA Honor Health
Scottsdale, Arizona, United States, 85258
United States, Maryland
Johns Hopkins SKCCC
Baltimore, Maryland, United States, 21231
Sponsors and Collaborators
Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
Stand Up To Cancer
Investigators
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Study Chair: Dung Le, MD Johns Hopkins SKCCC

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Responsible Party: Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins
ClinicalTrials.gov Identifier: NCT02048384     History of Changes
Other Study ID Numbers: J13146
NA_00090282 ( Other Identifier: JHMIRB )
First Posted: January 29, 2014    Key Record Dates
Last Update Posted: January 10, 2019
Last Verified: January 2019

Keywords provided by Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins:
rapamycin
metformin
pancreatic cancer
adenocarcinoma
metastatic

Additional relevant MeSH terms:
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Adenocarcinoma
Carcinoma
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Metformin
Sirolimus
Everolimus
Hypoglycemic Agents
Physiological Effects of Drugs
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antineoplastic Agents
Antifungal Agents
Immunosuppressive Agents
Immunologic Factors