NCT02048384

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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
22

participants targeted

Target at P25-P50 for phase_1

Timeline
Completed

Started Jun 2014

Longer than P75 for phase_1

Geographic Reach
1 country

2 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

January 23, 2014

Completed
6 days until next milestone

First Posted

Study publicly available on registry

January 29, 2014

Completed
4 months until next milestone

Study Start

First participant enrolled

June 10, 2014

Completed
3.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

February 1, 2018

Completed
1.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

September 1, 2019

Completed
Last Updated

April 12, 2021

Status Verified

April 1, 2021

Enrollment Period

3.6 years

First QC Date

January 23, 2014

Last Update Submit

April 9, 2021

Conditions

Metastatic Pancreatic Adenocarcinoma

Keywords

rapamycinmetforminpancreatic canceradenocarcinomametastatic

Outcome Measures

Primary Outcomes (1)

  • safety and feasibility

    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.

    1 year

Other Outcomes (4)

  • FDG uptake

    1 year

  • mTOR activity

    1 year

  • estimation of RR, TTP, PFS, OS

    1 year

  • +1 more other outcomes

Study Arms (2)

A - metformin alone

EXPERIMENTAL

metformin alone Arm A patients will receive metformin 850mg orally twice a day on a 28 day cycle.

Drug: metformin alone (Arm A)

B - metformin + rapamycin

ACTIVE COMPARATOR

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)Drug: rapamycin (Arm B)

Interventions

metformin alone (Arm A)DRUG

metformin alone

Also known as: Glumetza, Fortamet, Riomet, Glucophage
A - metformin alone
metformin (Arm B)DRUG

rapamycin + metformin

Also known as: Glumetza, Fortamet, Riomet, Glucophage
B - metformin + rapamycin
rapamycin (Arm B)DRUG

rapamycin + metformin

Also known as: Sirolimus, Rapamune
B - metformin + rapamycin

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Scottsdale Healthcare Hospitals DBA Honor Health

Scottsdale, Arizona, 85258, United States

Location

Johns Hopkins SKCCC

Baltimore, Maryland, 21231, United States

Location

MeSH Terms

Conditions

Pancreatic NeoplasmsAdenocarcinomaNeoplasm Metastasis

Interventions

MetforminSirolimus

Condition Hierarchy (Ancestors)

Digestive System NeoplasmsNeoplasms by SiteNeoplasmsEndocrine Gland NeoplasmsDigestive System DiseasesPancreatic DiseasesEndocrine System DiseasesCarcinomaNeoplasms, Glandular and EpithelialNeoplasms by Histologic TypeNeoplastic ProcessesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

BiguanidesGuanidinesAmidinesOrganic ChemicalsMacrolidesLactones

Study Officials

  • Dung Le, MD

    Johns Hopkins SKCCC

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

January 23, 2014

First Posted

January 29, 2014

Study Start

June 10, 2014

Primary Completion

February 1, 2018

Study Completion

September 1, 2019

Last Updated

April 12, 2021

Record last verified: 2021-04

Locations

US(2)