Study of Erlotinib and Metformin in Triple Negative Breast Cancer

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2014 by Columbia University
Sponsor:
Collaborators:
Susan G. Komen Breast Cancer Foundation
Astellas Pharma Inc
Information provided by (Responsible Party):
Matthew A. Maurer, Columbia University
ClinicalTrials.gov Identifier:
NCT01650506
First received: July 24, 2012
Last updated: July 22, 2014
Last verified: July 2014
  Purpose

Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast cancer patients.


Condition Intervention Phase
Breast Cancer
Drug: Metformin
Drug: Erlotinib
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Phase I Study of Erlotinib and Metformin in Triple Negative Breast Cancer

Resource links provided by NLM:


Further study details as provided by Columbia University:

Primary Outcome Measures:
  • The maximum tolerated dose of metformin in combination with a fixed dose of 150 mg erlotinib daily [ Time Frame: Five weeks ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 20
Study Start Date: July 2012
Estimated Study Completion Date: January 2016
Estimated Primary Completion Date: June 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Erlotinib + Metformin
This is a single arm phase 1 study. All patients will receive erlotinib and metformin.
Drug: Metformin
Due to frequent GI upset in patients starting metformin the dose will be titrated up to the assigned dose level. The first metformin dose level will be 850 mg twice daily and be escalated to its maximum FDA approved dose of 850 mg three times daily. Dose escalation will follow the standard 3 + 3 design. Dose limiting toxicities will be determined during the first 5 weeks of therapy.
Other Name: Glucophage
Drug: Erlotinib
Erlotinib dosing will start and remain at 150 mg daily.
Other Name: Tarceva

Detailed Description:

The goals of the study are to establish the maximum tolerated combined dosing of erlotinib and metformin as well as deciding if there is potential clinical utility of the combination in treating patients with triple negative breast cancer.

  Eligibility

Ages Eligible for Study:   18 Years to 79 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Confirmed pathologic diagnosis of triple negative breast cancer, OR Prior diagnosis of ER or PR positive breast cancer [HER2 negative] that is demonstrated to be both ER and PR negative (no or rare staining) on the patient's most recent biopsy.
  • Patients with measurable or non-measurable metastatic disease (RECIST 1.1).
  • At least one prior treatment for metastatic disease.
  • Availability of adequate tumor tissue for exploratory analysis and plan to obtain the material (see section 12.6).
  • Patients must have recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study. No chemotherapy or radiotherapy may be given within 2 weeks prior to the start of protocol treatment.
  • Patients must be ≥ 18 and < 80 years old.
  • Performance Status: ECOG 0-2.
  • Life expectancy of greater than 12 weeks.
  • Patients must have recovered from uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris or cardiac arrhythmia.
  • Required Laboratory Values: ANC ≥1,250/mm3, platelets ≥75,000/mm3, hemoglobin ≥8.5 g/dL, total bilirubin ≤1.5 x ULN, AST/ALT ≤3.0 x ULN, alkaline phosphatase ≤2.5 x ULN, Patients must have either a normal serum creatinine (<= IULN) OR estimated creatinine clearance ≥ 60 ml/min (Cockcroft-Gault formula) within 14 days prior to registration.
  • Concomitant Medications: Erlotinib is primarily metabolized by CYP3A4. Patients CANNOT be receiving enzyme-inducing or enzyme inhibiting agents listed here: Inhibitors: Amiodarone, Amprenavir, Atazanavir, Chloramphenicol, Clarithromycin, Conivaptan, Cyclosporine, Darunavir, Dasatinib, Delavirdine, Diltiazem, Erythromycin, Fluconazole, Fluoxetine, Fluvoxamine, Fosamprenavir, Imatinib, Indinavir, Isoniazid, Itraconazole, Ketoconazole, Lapatinib, Miconazole, Nefazodone, Nelfinavir, Posaconazole, Ritonavir, Quinupristin, Saquinavir, Tamoxifen, Telithromycin, Troleandomycin, Verapamil, Voriconazole. Inducers: Aminoglutethimide,Bexarotene, Bosentan, Carbamazepine, Efavirenz, Fosphenytoin, Griseofulvin, Modafinil, Nafcillin, Nevirapine, Oxcarbazepine, Phenobarbital, Phenytoin, Primidone, Rifabutin, Rifampin, Rifapentine, St. John's wort, Sulfadimidine, Sulfinpyrazone, Troglitazone, Troleandomycin. All concomitant medications must be recorded.
  • Sexually Active Patients: For all sexually active patients, the use of adequate contraception (hormonal or barrier method of birth control) will be required prior to study entry and for the duration of study participation. Non-pregnant status will be determined in all women of childbearing potential.
  • Patients must have signed an approved informed consent.

Exclusion Criteria:

  • Active CNS disease

    a. Subjects with a history of CNS metastases or cord compression are allowable if they have been clinically stable for at least 6 weeks since completion of definitive treatment, are off steroids (if the steroids were part of the CNS disease treatment), and in the case of brain metastases, have stable or improved imaging at least 6 weeks after completion of their definitive treatment.

  • Any serious medical or psychiatric illness that would prevent either the giving of informed consent or the receipt of treatment.
  • Patients pregnant or nursing.
  • Patients who have used tobacco or nicotine products or medications within the last three months given their significant effect on erlotinib drug levels.
  • Diabetes. Defined as HgbA1C ≥ 6.5%.
  • Prior metformin treatment OR EGFR targeted therapy.
  • Rapidly progressive disease as judged by the investigator (Examples include rapidly deteriorating performance status or symptomatic lymphangitic spread).
  • Patient has any condition associated with increased risk of metformin-associated lactic acidosis (e.g. congestive heart failure defined as New York Heart Association {NYHA} Class III or IV functional status, history of acidosis of any type; habitual intake of 3 or more alcoholic beverages per day).
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01650506

Contacts
Contact: Ramona Jayasena 212.304.5579 rj2002@columbia.edu

Locations
United States, New York
Columbia University Recruiting
New York, New York, United States, 10032
Contact: Ramona Jayasena    212-304-5579    rj2002@columbia.edu   
Sub-Investigator: Dawn L Hershman, MD, MS         
Principal Investigator: Matthew A Maurer, MD         
Sponsors and Collaborators
Matthew A. Maurer
Susan G. Komen Breast Cancer Foundation
Astellas Pharma Inc
Investigators
Principal Investigator: Matthew A Maurer, MD Columbia University
  More Information

No publications provided

Responsible Party: Matthew A. Maurer, Assistant Professor of Medicine, Columbia University
ClinicalTrials.gov Identifier: NCT01650506     History of Changes
Other Study ID Numbers: AAAF3743
Study First Received: July 24, 2012
Last Updated: July 22, 2014
Health Authority: United States: Institutional Review Board

Keywords provided by Columbia University:
Triple Negative
Basal-like

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Neoplasms
Breast Diseases
Skin Diseases
Metformin
Erlotinib
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 26, 2014