Breast NeoplasmsPhase 2NCT01499160
Letrozole and Lapatinib Followed by Everolimus in Women With Advanced Breast Cancer
A Phase 2 study testing letrozole, lapatinib and everolimus in people with Breast Neoplasms and Endocrine Breast Diseases, run by University of Maryland, Baltimore at 1 site in United States.
Trial summary
About a third of patients with breast cancer are usually treated by hormone pills called tamoxifen and aromatase inhibitors. Aromatase inhibitors are drugs that stop female hormone production. Female hormone or estrogen is an important hormone for the growth of breast cancer cells. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Neoplasms, Endocrine Breast Diseases, Neoplasm Metastasis
- What is being tested?
- letrozole, lapatinib and everolimus
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 7 participants
- Where
- 1 siteUnited States
- Study dates
- May 2012to Dec 2016
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Female greater than or equal to 18 years.
- Histologically confirmed breast adenocarcinoma with incurable progressing local-regional or metastatic.
- ER and/or PR positivity of primary and/or secondary tumor.
- Patients must have measurable or evaluable disease.
- Evidence of disease progression or relapse while on or less than 6 months off aromatase inhibitors or tamoxifen either in adjuvant or first line metastatic setting.
- Postmenopausal
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- Patients may have received up to one prior chemotherapy regimen for stage IV breast cancer. Prior chemotherapy in the adjuvant and/or neoadjuvant setting is permitted. Chemotherapy must be finished at least 2 weeks prior to enrollment.
- ECOG performance status <2
- Fasting cholesterol ≤300 mg/dL OR ≤7.75 mmol/LAND fasting triglycerides ≤ 2.5 x ULN despite appropriate treatment.
- Patients must have adequate organ function as defined by the protocol.
- Stratification 1:
- HER2 positive in the primary or secondary tumor tissue
- Prior trastuzumab therapy is allowed but NOT required. However, trastuzumab should be discontinued at least 3 weeks prior to enrollment.
- Stratification 2:
- HER2 negative in the primary or secondary tumor tissue
Who cannot join
- Patients receiving any other investigational agents.
- Prior exposure to lapatinib, everolimus, or other mTOR inhibitors.
- History of allergic reactions or hypersensitivity to compounds similar to everolimus, lapatinib, or letrozole.
- Patients who have any severe and/or uncontrolled medical conditions that could affect their participation such as:
- Left ventricular ejection fraction (LVEF) < 50%
- Unstable angina, symptomatic congestive heart failure, myocardial infarction within 6 months, serious uncontrolled cardiac arrhythmia or any other clinically significant cardiac disease.
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- Severely impaired lung function as defined as spirometry and DLCO that is 50% of the normal predicted value and/or O2 saturation that is ≤ 88% at rest on room air.
- Uncontrolled diabetes
- Active or uncontrolled severe infection
- Patients with QTc interval > 0.47 seconds.
- Significant chronic or acute gastrointestinal disorder with diarrhea as a major symptom.
- Prior exposure to more than 360 mg/m2 doxorubicin, more than 120 mg/m2mitoxantrone, or more than 90 mg/m2idarubicin, or elevated baseline cardiac troponin I.
- Patients with active CNS metastasis and/or carcinomatous meningtitis. However, patients with CNS metastasis who have completed a therapy and are clinically stable for 3 weeks as defined as: (1) no evidence of new or enlarging CNS metastasis and (2) off steroids and/or anticonvulsants.
- Patient is known to be HIV, Hepatitis B, or Hepatitis C-positive (these tests are not required).
- Patients with current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease).
- Patients with INR ≥ 2 or PTT ≥ 2 x upper normal limit.
- Previous or current systemic malignancy other than breast cancer within the past 3 years other than carcinoma in situ of the cervix or basal/squamous carcinoma of the skin.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Maryland Marlene & Stewart Greenebaum Cancer Center
Baltimore, Maryland, 21201
About this study
Official title: GCC 0901- A Phase II Study of Letrozole in Combination With Lapatinib Followed by an Addition of Everolimus in Postmenopausal Women With Advanced Endocrine Resistant Breast Cancer
About a third of patients with breast cancer are usually treated by hormone pills called tamoxifen and aromatase inhibitors. Aromatase inhibitors are drugs that stop female hormone production. Female hormone or estrogen is an important hormone for the growth of breast cancer cells. Letrozole is one of the aromatase inhibitors that is approved by the FDA and has been used to treat breast cancer since 1997. However, hormone pills usually work for about 6-10 months in most patients. Later on, breast cancer will start to grow again. This condition when hormone pills or endocrine therapy no longer work is called "endocrine resistant" breast cancer. The scientists here at University of Maryland have discovered how these cancer cells can become resistant to hormone pills. In our laboratory tests, the investigators found that lapatinib and everolimus can reverse this resistance and make letrozole work again. However, it is not known if the drugs can reverse the resistance in humans.
The purpose of this study is to find out whether the combination of letrozole, lapatinib, and everolimus is effective in women with breast cancer when hormone pills no longer work.
Read more
Lapatinib is an anti-cancer drug that is already approved by the Food and Drug Administration (FDA). It is the standard of care for the treatment of a particular type of breast cancer called human epithelial growth factor receptor 2 (HER2)-positive breast cancer. HER2 is a protein involved in the growth of some cancer cells. This study will also include patients with HER2-negative breast cancer. This means that the cancer cells in these patients do not depend on the HER2 protein. The use of lapatinib in these patients is considered experimental.
Everolimus is also an anti-cancer drug that is approved by the FDA for kidney cancer. Initial studies in mice and later studies in women with breast cancer have shown that everolimus may also slow the growth of breast cancer. The use of everolimus is experimental in this study.
Read the detailed description
This is a single-institution clinical trial. Patients will be stratified according to the HER2 status:
Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue
In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. We do not expect any significant toxicity from this combination since the previous study of lapatinib and letrozole showed that this combination is safe with no grade 3-4 toxicities observed. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus. The outcome of each group will continue to be assessed separately. We do not expect to see additional serious toxicity from adding everolimus to the combination of lapatinib and letrozole. All of the treatment will be continued until disease progression.
- Being tested
- letrozole, lapatinib, everolimus
- Keywords
- endocrine resistant, everolimus, lapatinib, letrozole
- Medical subject headings
- Breast Neoplasms, Breast Diseases, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
letrozoleDrug
Also called Femara
Drug is are to be taken orally. 2.5 mg once daily
lapatinibDrug
Also called Tykerb
Drug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression)
everolimusDrug
Also called Afinitor
Drug is to be taken orally. 5 mg once daily.
| Study group | Role | What they receive |
|---|---|---|
| HER2-positive or negative | Experimental | Lapatinib 1,500 mg/day + letrozole 2.5 mg/day until progression followed by everolimus 5 mg/day + letrozole 2.5 mg/day + lapatinib 1,250 mg/day. Receives: Drug: letrozole; Drug: lapatinib; Drug: everolimus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib.
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression.
Clinical benefit rate is defined as complete response+partial response+ stable disease. All participants will be treated with the combination of letrozole and lapatinib. Once the participant progresses on this regimen, the participant will be treated with everolimus, letrozole and lapatinib until they progress.
Measured: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Secondary outcomes (1)
PROGRESSION FREE SURVIVAL TUMOR ASSESSMENT
Patients treated with the combination of Letrozole and Lapatinib will provide tumor biopsy sample
Measured: From date of study entry until 4 weeks after removal from study or until death (whichever occurs first) up to 24 months.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Dec 2011 (estimated)
- Study startMay 2012
- Primary completionNov 2014
- Study completionDec 2016
Why it stopped: low accrual
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Breast NeoplasmsStudies of the same condition, open and under way.
- More trials run by University of Maryland, BaltimoreThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- sequential treatment assignment, no masking is done
- Masking
- None (open label)
- Enrolment
- 7 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Maryland, Baltimore
- Sponsor type
- University, hospital or other
- Collaborators
- Novartis Pharmaceuticals, GlaxoSmithKline
- Responsible party
- Principal investigator, Katherine Tkaczuk, University of Maryland, Baltimore
- Investigators
- Katherine Tkaczuk, MD, Principal investigator, University of Maryland Marlene & Stewart Greenebaum Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01499160
- Sponsor's protocol ID
- HP-00040802; GCC 0901
- Other IDs
- GCC 0901
- Status last verified
- Feb 2022
- First submitted
- 14 Dec 2011
- Last updated
- 11 Feb 2022
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Feb 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- GCC 0901- A Phase II Study of Letrozole in Combination With Lapatinib Followed by an Addition of Everolimus in Postmenopausal Women With Advanced Endocrine Resistant Breast Cancer
- ClinicalTrials.gov ID
- NCT01499160
- Acronym / sponsor ID
- HP-00040802; GCC 0901
- Keywords
- endocrine resistant, everolimus, lapatinib, letrozole
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 7 participants (actual)
- Lead sponsor
- University of Maryland, BaltimoreUniversity, hospital or other
- Collaborators
- Novartis Pharmaceuticals, GlaxoSmithKline
- Study start
- May 2012 (actual)
- Primary completion
- Nov 2014 (actual)
- Study completion
- Dec 2016 (actual)
- First posted
- 26 Dec 2011 (estimated)
- Results
- Posted 6 Mar 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
About a third of patients with breast cancer are usually treated by hormone pills called tamoxifen and aromatase inhibitors. Aromatase inhibitors are drugs that stop female hormone production. Female hormone or estrogen is an important hormone for the growth of breast cancer cells. Letrozole is one of the aromatase inhibitors that is approved by the FDA and has been used to treat breast cancer since 1997. However, hormone pills usually work for about 6-10 months in most patients. Later on, breast cancer will start to grow again. This condition when hormone pills or endocrine therapy no longer work is called "endocrine resistant" breast cancer. The scientists here at University of Maryland have discovered how these cancer cells can become resistant to hormone pills. In our laboratory tests, the investigators found that lapatinib and everolimus can reverse this resistance and make letrozole work again. However, it is not known if the drugs can reverse the resistance in humans.
The purpose of this study is to find out whether the combination of letrozole, lapatinib, and everolimus is effective in women with breast cancer when hormone pills no longer work.
Lapatinib is an anti-cancer drug that is already approved by the Food and Drug Administration (FDA). It is the standard of care for the treatment of a particular type of breast cancer called human epithelial growth factor receptor 2 (HER2)-positive breast cancer. HER2 is a protein involved in the growth of some cancer cells. This study will also include patients with HER2-negative breast cancer. This means that the cancer cells in these patients do not depend on the HER2 protein. The use of lapatinib in these patients is considered experimental.
Everolimus is also an anti-cancer drug that is approved by the FDA for kidney cancer. Initial studies in mice and later studies in women with breast cancer have shown that everolimus may also slow the growth of breast cancer. The use of everolimus is experimental in this study.
Detailed description
This is a single-institution clinical trial. Patients will be stratified according to the HER2 status:
Group 1: HER2-positive in the tumor tissue Group 2: HER2 negative in the tumor tissue
In the first part of the study, all of the patients will receive the combination of lapatinib 1,500 mg/day and letrozole 2.5 mg/day. We do not expect any significant toxicity from this combination since the previous study of lapatinib and letrozole showed that this combination is safe with no grade 3-4 toxicities observed. Restaging scans (CT scan, MRI, or bone scan) will be obtained after every 12 weeks of treatment. In those patients who progress from any group, everolimus 5 mg/day will be added to letrozole and lapatinib will be reduced to 1,250 mg/day as per the SWOG phase I study of lapatinib and everolimus. The outcome of each group will continue to be assessed separately. We do not expect to see additional serious toxicity from adding everolimus to the combination of lapatinib and letrozole. All of the treatment will be continued until disease progression.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- sequential treatment assignment, no masking is done
| Arm | Type | Receives |
|---|---|---|
| HER2-positive or negative | Experimental | Drug: letrozole, Drug: lapatinib, Drug: everolimusLapatinib 1,500 mg/day + letrozole 2.5 mg/day until progression followed by everolimus 5 mg/day + letrozole 2.5 mg/day + lapatinib 1,250 mg/day. |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (15 listed)
- Female greater than or equal to 18 years.
- Histologically confirmed breast adenocarcinoma with incurable progressing local-regional or metastatic.
- ER and/or PR positivity of primary and/or secondary tumor.
- Patients must have measurable or evaluable disease.
- Evidence of disease progression or relapse while on or less than 6 months off aromatase inhibitors or tamoxifen either in adjuvant or first line metastatic setting.
Key exclusion criteria (17 listed)
- Patients receiving any other investigational agents.
- Prior exposure to lapatinib, everolimus, or other mTOR inhibitors.
- History of allergic reactions or hypersensitivity to compounds similar to everolimus, lapatinib, or letrozole.
- Patients who have any severe and/or uncontrolled medical conditions that could affect their participation such as:
- Patients with QTc interval > 0.47 seconds.
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 |
|---|---|---|
| letrozoleAlso: FemaraDrug is are to be taken orally. 2.5 mg once daily | Drug | HER2-positive or negative |
| lapatinibAlso: TykerbDrug is to be taken orally. 1,500 mg once daily in the first part of the study and then 1,250 mg once daily in the second part of the study (after initial progression) | Drug | HER2-positive or negative |
| everolimusAlso: AfinitorDrug is to be taken orally. 5 mg once daily. | Drug | HER2-positive or negative |
Primary outcome
Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib.
Time frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months
Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI: Complete Response (CR), Disappearance of all target lesions; Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Progression, as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for disease progression. Clinical benefit rate is defined as complete response+partial response+ stable disease. All participants will be treated with the combination of letrozole and lapatinib. Once the participant progresses on this regimen, the participant will be treated with everolimus, letrozole and lapatinib until they progress.
1 secondary outcome
PROGRESSION FREE SURVIVAL TUMOR ASSESSMENT
Time frame: From date of study entry until 4 weeks after removal from study or until death (whichever occurs first) up to 24 months.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 11 Feb 2022.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Katherine Tkaczuk, MD principal investigator
University of Maryland Marlene & Stewart Greenebaum Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing letrozole, lapatinib and everolimus in people with Breast Neoplasms and Endocrine Breast Diseases, run by University of Maryland, Baltimore 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 15 inclusion and 17 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: stopped early, as of the sponsor's last update on 11 Feb 2022. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 6 Mar 2018). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Clinical Benefit Rate of Patients Treated With the Combination of Letrozole and Lapatinib and Then After Progression, Treated With Everolimus, Letrozole and Lapatinib. (time frame: From date of study entry until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 months). 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 11 Feb 2022.