Study of Erlotinib and Metformin in Triple Negative Breast Cancer

NCT01650506 | Completed Phase 1 DMC FDA Drug

• 1 other identifier: AAAF3743
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 1

Brief Summary

Extended phase 1 trial of combined metformin and erlotinib in advanced triple negative breast cancer patients. The goals of the study are to establish the maximum tolerated combined dosing of erlotinib and metformin as well as deciding if there is a potential clinical utility of the combination in treating patients with triple negative breast cancer.

Conditions

Breast Cancer

Keywords

Triple Negative; Basal-like

Outcome Measures

Primary Outcomes (1)

• The maximum tolerated dose of metformin in combination with a fixed dose of 150 mg erlotinib daily

  The highest dose of a treatment that does not cause unacceptable side effects.

  Up to 5 weeks

Study Arms (1)

Erlotinib + Metformin

EXPERIMENTAL

This is a single arm phase 1 study. All patients will receive erlotinib and metformin.

Drug: Metformin; Drug: Erlotinib

Interventions

Metformin DRUG

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.

Also known as: Glucophage

Erlotinib + Metformin

Erlotinib DRUG

Erlotinib dosing will start and remain at 150 mg daily.

Also known as: Tarceva

Erlotinib + Metformin

Eligibility Criteria

• Age: 18 Years - 79 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Confirmed pathologic diagnosis of triple negative breast cancer, OR Prior diagnosis of ER or P-R positive breast cancer \[HER2 negative\] that is demonstrated to be both ER and P-R 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.
• 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: Eastern Cooperative Oncology Group (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: Absolute neutrophil count (ANC) ≥1,250/mm3, platelets ≥75,000/mm3, hemoglobin ≥8.5 g/dL, total bilirubin ≤1.5 x ULN, Aspartate Aminotransferase (AST)/Alanine Aminotransferase (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. The non-pregnant status will be determined in all women of childbearing potential.
• Patients must have signed an approved informed consent.

You may not qualify if:

• Active central nervous system (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).

Sponsors & Collaborators

• Columbia University: lead
• Susan G. Komen Breast Cancer Foundation: collaborator
• Astellas Pharma Inc: collaborator

Study Sites (1)

Columbia University

New York, New York, 10032, United States

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Metformin; Erlotinib Hydrochloride

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Biguanides; Guanidines; Amidines; Organic Chemicals; Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Study Officials

• Kevin Kalinsky, MD

  Columbia University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assistant Professor of Medicine

Study Record Dates

• First Submitted: July 24, 2012
• First Posted: July 26, 2012
• Study Start: July 1, 2012
• Primary Completion: June 1, 2016
• Study Completion: June 1, 2016
• Last Updated: August 30, 2017

Record last verified: 2017-08

Locations

US (1)