Breast CancerPhase 1NCT01650506
Study of Erlotinib and Metformin in Triple Negative Breast Cancer
A Phase 1 study testing Metformin and Erlotinib in people with Breast Cancer, run by Columbia University at 1 site in United States.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 to 79 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Metformin and Erlotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 8 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2012to Jun 2016
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 79 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
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- 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.
Who cannot join
- Active central nervous system (CNS) disease
- 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%.
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- 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).
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Phase I Study of Erlotinib and Metformin in Triple Negative Breast Cancer
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.
Read the detailed description
Breast cancer has several different subtypes based upon measurement of expression of proteins found on the surface of the cancer cells. Cancers that lack expression of three of these proteins, namely the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), are termed triple negative. By studying the molecular attributes of breast cancer cells from a large group of breast cancer patients, a profile of markers enriched in triple negative breast cancers (TNBC) was discovered. This profile includes loss of expression of the protein, Phosphatase and Tensin homolog (PTEN), increased expression of the protein, epidermal growth factor receptor (EGFR), and disruption of the cells ability to repair DNA. These alterations also allow the tumor to thrive and likely evade treatment. Observation has been made that the drug combination of metformin and erlotinib can inhibit triple negative cells with these alterations. A clinical trial will be conducted to test the ability of patients to tolerate the treatment (Phase I trial). This trial will be available to triple negative breast cancer patients with metastatic disease. Other goals of the study will be to confirm that the drugs are working properly and whether or not there are enough responses to the treatment to warrant additional studies. If the treatment proves to be effective, even if only in a subset of triple negative patients, future studies will focus on validating biomarkers that can identify patients that will respond to the drug combination, as well as discovering how cells become resistant to the treatment. The research has the potential to advance a new effective treatment for a highly lethal disease and thus could prolong patient survivals while maintaining a high quality of life.
- Conditions
- Breast Cancer
- Keywords
- Triple Negative, Basal-like
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MetforminDrug
Also called Glucophage
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.
ErlotinibDrug
Also called Tarceva
Erlotinib dosing will start and remain at 150 mg daily.
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib + Metformin | Experimental | This is a single arm phase 1 study. All patients will receive erlotinib and metformin. Receives: Drug: Metformin; Drug: Erlotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 5 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jul 2012 (estimated)
- Study startJul 2012
- Primary completionJun 2016
- Study completionJun 2016
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 8 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Collaborators
- Susan G. Komen Breast Cancer Foundation, Astellas Pharma Inc
- Responsible party
- Principal investigator, Kevin Kalinsky, Columbia University
- Investigators
- Kevin Kalinsky, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01650506
- Sponsor's protocol ID
- AAAF3743
- Status last verified
- Aug 2017
- First submitted
- 24 Jul 2012
- Last updated
- 30 Aug 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Aug 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of Erlotinib and Metformin in Triple Negative Breast Cancer
- ClinicalTrials.gov ID
- NCT01650506
- Acronym / sponsor ID
- AAAF3743
- Conditions
- Breast Cancer
- Keywords
- Triple Negative, Basal-like
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 8 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Collaborators
- Susan G. Komen Breast Cancer Foundation, Astellas Pharma Inc
- Study start
- Jul 2012 (actual)
- Primary completion
- Jun 2016 (actual)
- Study completion
- Jun 2016 (actual)
- First posted
- 26 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
Breast cancer has several different subtypes based upon measurement of expression of proteins found on the surface of the cancer cells. Cancers that lack expression of three of these proteins, namely the estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2), are termed triple negative. By studying the molecular attributes of breast cancer cells from a large group of breast cancer patients, a profile of markers enriched in triple negative breast cancers (TNBC) was discovered. This profile includes loss of expression of the protein, Phosphatase and Tensin homolog (PTEN), increased expression of the protein, epidermal growth factor receptor (EGFR), and disruption of the cells ability to repair DNA. These alterations also allow the tumor to thrive and likely evade treatment. Observation has been made that the drug combination of metformin and erlotinib can inhibit triple negative cells with these alterations. A clinical trial will be conducted to test the ability of patients to tolerate the treatment (Phase I trial). This trial will be available to triple negative breast cancer patients with metastatic disease. Other goals of the study will be to confirm that the drugs are working properly and whether or not there are enough responses to the treatment to warrant additional studies. If the treatment proves to be effective, even if only in a subset of triple negative patients, future studies will focus on validating biomarkers that can identify patients that will respond to the drug combination, as well as discovering how cells become resistant to the treatment. The research has the potential to advance a new effective treatment for a highly lethal disease and thus could prolong patient survivals while maintaining a high quality of life.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib + Metformin | Experimental | Drug: Metformin, Drug: ErlotinibThis is a single arm phase 1 study. All patients will receive erlotinib and metformin. |
Who may qualify
- Ages
- 18 to 79 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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.
Key exclusion criteria (9 listed)
- Active central nervous system (CNS) disease
- 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%.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MetforminAlso: GlucophageDue 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. | Drug | Erlotinib + Metformin |
| ErlotinibAlso: TarcevaErlotinib dosing will start and remain at 150 mg daily. | Drug | Erlotinib + Metformin |
Primary outcome
The maximum tolerated dose of metformin in combination with a fixed dose of 150 mg erlotinib daily
Time frame: Up to 5 weeks
The highest dose of a treatment that does not cause unacceptable side effects.
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Aug 2017.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Kalinsky, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Metformin and Erlotinib in people with Breast Cancer, run by Columbia University at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 13 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 30 Aug 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The maximum tolerated dose of metformin in combination with a fixed dose of 150 mg erlotinib daily (time frame: Up to 5 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Aug 2017.