Study of Erlotinib and Metformin in Triple Negative Breast Cancer | RxWiki

Study of Erlotinib and Metformin in Triple Negative Breast Cancer

Overview[ - collapse ][ - ]

Purpose	Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast cancer patients.
Condition	Breast Cancer
Intervention	Drug: Metformin Drug: Erlotinib
Phase	Phase 1
Sponsor	Matthew A. Maurer
Responsible Party	Columbia University
ClinicalTrials.gov Identifier	NCT01650506
First Received	July 24, 2012
Last Updated	July 25, 2012
Last verified	July 2012

Tracking Information[ + expand ][ + ]

First Received Date	July 24, 2012
Last Updated Date	July 25, 2012
Start Date	July 2012
Estimated Primary Completion Date	January 2015
Current 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]
Current Secondary Outcome Measures	Not Provided

Descriptive Information[ + expand ][ + ]

Brief Title	Study of Erlotinib and Metformin in Triple Negative Breast Cancer
Official Title	Phase I Study of Erlotinib and Metformin in Triple Negative Breast Cancer
Brief Summary	Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast cancer patients.
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.
Study Type	Interventional
Study Phase	Phase 1
Study Design	Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Condition	Breast Cancer
Intervention	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 Names: GlucophageDrug: Erlotinib Erlotinib dosing will start and remain at 150 mg daily. Other Names: Tarceva
Study Arm (s)	Experimental: Erlotinib + Metformin This is a single arm phase 1 study. All patients will receive erlotinib and metformin.

Recruitment Information[ + expand ][ + ]

Recruitment Status	Recruiting
Estimated Enrollment	20
Estimated Completion Date	January 2015
Estimated Primary Completion Date	June 2014
Eligibility 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).
Gender	Female
Ages	18 Years
Accepts Healthy Volunteers	No
Contacts	Contact: Ramona Jayasena 212.304.5579 rj2002@columbia.edu
Location Countries	United States

Administrative Information[ + expand ][ + ]

NCT Number	NCT01650506
Other Study ID Numbers	AAAF3743
Has Data Monitoring Committee	Yes
Information Provided By	Columbia University
Study Sponsor	Matthew A. Maurer
Collaborators	Susan G. Komen Breast Cancer Foundation Astellas Pharma Inc
Investigators	Principal Investigator: Matthew A Maurer, MD Columbia University
Verification Date	July 2012

Locations[ + expand ][ + ]