Breast CancerPhase 1NCT00574366
Erlotinib and Everolimus in Treating Patients With Metastatic Breast Cancer
A Phase 1 study testing erlotinib and RAD001 in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 3 sites in United States.
Trial summary
RATIONALE: Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib together with everolimus may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Breast Cancer
- What is being tested?
- erlotinib and RAD001
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 14 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2005to Feb 2009
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Menopausal status not specified
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- SGOT and SGPT ≤ 2.5 times ULN
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- Albumin > 30 g/L
- Creatinine ≤ 1.5 upper limit of normal
- INR normal provided the patient is not on warfarin therapy
- Not pregnant or nursing
- Negative pregnancy test for premenopausal patients
- Fertile patients must use effective barrier method contraception during and for 3 months after completion of study treatment
- Patients must be disease-free of prior invasive cancers for > 5 years with the exception of basal cell or squamous cell cancer of the skin or cervical carcinoma in situ
- See Disease Characteristics
- Prior trastuzumab (Herceptin®) in the first-line treatment of metastatic breast cancer is required for patients who have HER2/neu overexpressing tumors
- More than 6 months since prior cardiac angioplasty or stenting
- Use of endocrine therapy (i.e., aromatase inhibitors, fulvestrant, tamoxifen or ovarian ablation) in the first-line treatment of metastatic breast cancer is required for patients who have estrogen receptor and or progesterone receptor expressing tumors
- Concurrent endocrine therapy is not allowed
- Patients may receive concurrent radiotherapy to painful bone metastases or areas of impending bone fracture as long as radiotherapy is initiated prior to study entry
- Patients who have received prior radiotherapy must have recovered from toxicity induced by this treatment
- More than 3 weeks since prior chemotherapy, biological or hormonal therapy while on protocol therapy.
- No other concurrent antineoplastic or antitumor agents, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
Who cannot join
- Serious or non-healing active wound, ulcer, or bone fracture
- Known human immunodeficiency virus positivity
- Uncontrolled intercurrent illness including, but not limited to, any of the following
- Ongoing or active infection requiring parenteral antibiotics
- Impairment of lung function (COPD, lung conditions requiring oxygen therapy)
- Symptomatic congestive heart failure (New York Heart Association class III or IV heart disease)
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- Unstable angina pectoris or myocardial infarction within the past 6 months
- Uncontrolled hypertension (i.e., systolic blood pressure > 180 mm Hg or diastolic blood pressure > 100 mm Hg, found on two consecutive measurements separated by a 1-week period despite adequate medical support)
- Clinically significant cardiac arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia that is symptomatic or requires treatment)
- Uncontrolled diabetes
- Psychiatric illness/social situations that would compromise patient safety or limit compliance with study requirements including maintenance of a compliance/pill diary
- PRIOR CONCURRENT THERAPY:
- More than 3 prior chemotherapy treatments in the metastatic setting
- This restriction does not include endocrine therapies or single agent biologic therapies (i.e., trastuzumab [Herceptin®])
- Use of steroids or immunosuppressants
- Use of CYP3A4 modifiers
- Concurrent therapy with trastuzumab (Herceptin®)
- Use of growth support factors (e.g., filgrastim [G-CSF], sargramostim [GM-CSF], recombinant erythropoietin) during the phase I portion of the study
- Other concurrent investigational agents
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center at Franklin
Nashville, Tennessee, 37064
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
About this study
Official title: A Phase I/II Trial of an Oral MTOR Protein Kinase Inhibitor (Everolimus, RAD001) in Combination With an Oral EGFR Tyrosine Kinase Inhibitor (Erlotinib, Tarceva™) In Patients With Metastatic Breast Cancer
RATIONALE: Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib together with everolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving erlotinib together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the safety of everolimus given in combination with erlotinib hydrochloride in patients with metastatic breast cancer (phase I).
- To determine the antitumor activity of the combination (phase II).
- Determine the rate of clinical benefit (complete response + partial response + stable disease for at least 6 months) in patients with metastatic breast cancer (phase II).
Secondary
- To determine the time to progression.
- To determine PTEN, pAkt, pP70S6K1 and pEGFR in primary tumors at baseline.
OUTLINE: This is an open-label, dose escalation phase I study followed by an open-label phase II study.
- Phase I: Patients receive escalating doses of oral everolimus and oral erlotinib hydrochloride once daily until the maximum tolerated dose (MTD) is determined. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the MTD is reached, the recommended dose to be used in the phase II portion of the study is identified.
- Phase II: Patients receive oral everolimus and oral erlotinib hydrochloride as in phase I at the recommended phase II dose determined in phase I.
Patients undergo tissue collection to evaluate tumor levels of PTEN, pAkt, pP70S6K1, and pEGFR at baseline in order to identify predictors of therapeutic response.
After completion of study treatment, patients are followed every 3 months for 2 years (from study entry), every 6 months for 3 years, and annually thereafter.
NOTE: Phase I completed. Investigator did not proceed with Phase II
- Conditions
- Breast Cancer
- Being tested
- erlotinib, RAD001
- Keywords
- recurrent breast cancer, stage IV breast cancer, male breast cancer
- Medical subject headings
- Breast Neoplasms, Breast Neoplasms, Male
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinibDrug
Also called Tarceva (OSI-774)
Levels:
- 1 Erlotinib 50 mg/d
- 2 Erlotinib 50 mg/d
- 1 Erlotinib 100 mg/d
- 2 Erlotinib 100 mg/d
- 3 Erlotinib 150 mg/d
- 4 Erlotinib 150 mg/d
RAD001Drug
Also called everolimus
Levels
minus 1: RAD001 2.5 mg/d
minus 2: RAD001 2.5 every other day
- RAD001 2.5 mg per day
- RAD001 5 mg per day
- RAD001 10 mg per day
- RAD001 10 mg per day
| Study group | Role | What they receive |
|---|---|---|
| Erlotinib/RAD001 Ph I | Experimental | Tarceva (OSI-774; erlotinib) Everolimus (RAD001)
Study did not progress to Phase II:
Experimental: Erlotinib/RAD001 Phase II Maximum tolerated dose of erlotinib (Tarceva,OSI-774) and RAD001 (Everolimus) Receives: Drug: erlotinib; Drug: RAD001 |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose (MTD) of RAD001 given in combination with erlotinib (Phase I)
MTD will be the dose level at which fewer than 2 of 6 (or 33% of) patients experience dose limiting toxicity (DLT), starting at first 4 weeks.
Measured: at 4 weeks
Anti-tumor activity of RAD001 in combination with erlotinib (Phase II)
Clinical benefit based upon number of patients with complete response (CR), partial response (PR), and stable disease (SD). Responses are determined by Response Evaluation in Solid Tumors (RECIST)criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
Measured: at 6 months
Secondary outcomes (1)
Time to progression (Phase II)
Duration of time to progression of disease.
Measured: from study entry to disease progression
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted17 Dec 2007 (estimated)
- Study startDec 2005
- Primary completionJan 2009
- Study completionFeb 2009
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.
- 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
- 14 participants (actual)
Sponsor and investigators
- Lead sponsor
- Vanderbilt-Ingram Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Principal investigator, Ingrid Mayer, MD, Vanderbilt-Ingram Cancer Center
- Investigators
- Ingrid Mayer, MD, Study chair, Vanderbilt-Ingram Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00574366
- Sponsor's protocol ID
- VICC BRE 0523
- Other IDs
- VU-VICC-BRE-0523
- Status last verified
- May 2016
- First submitted
- 14 Dec 2007
- Last updated
- 10 May 2016
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 10 May 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I/II Trial of an Oral MTOR Protein Kinase Inhibitor (Everolimus, RAD001) in Combination With an Oral EGFR Tyrosine Kinase Inhibitor (Erlotinib, Tarceva™) In Patients With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00574366
- Acronym / sponsor ID
- VICC BRE 0523
- Conditions
- Breast Cancer
- Keywords
- recurrent breast cancer, stage IV breast cancer, male breast cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 14 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2005
- Primary completion
- Jan 2009 (actual)
- Study completion
- Feb 2009 (actual)
- First posted
- 17 Dec 2007 (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.
RATIONALE: Erlotinib and everolimus may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving erlotinib together with everolimus may kill more tumor cells.
PURPOSE: This phase I/II trial is studying the side effects and best dose of giving erlotinib together with everolimus and to see how well it works in treating patients with metastatic breast cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the safety of everolimus given in combination with erlotinib hydrochloride in patients with metastatic breast cancer (phase I).
- To determine the antitumor activity of the combination (phase II).
- Determine the rate of clinical benefit (complete response + partial response + stable disease for at least 6 months) in patients with metastatic breast cancer (phase II).
Secondary
- To determine the time to progression.
- To determine PTEN, pAkt, pP70S6K1 and pEGFR in primary tumors at baseline.
OUTLINE: This is an open-label, dose escalation phase I study followed by an open-label phase II study.
- Phase I: Patients receive escalating doses of oral everolimus and oral erlotinib hydrochloride once daily until the maximum tolerated dose (MTD) is determined. Treatment repeats every 4 weeks in the absence of disease progression or unacceptable toxicity. Once the MTD is reached, the recommended dose to be used in the phase II portion of the study is identified.
- Phase II: Patients receive oral everolimus and oral erlotinib hydrochloride as in phase I at the recommended phase II dose determined in phase I.
Patients undergo tissue collection to evaluate tumor levels of PTEN, pAkt, pP70S6K1, and pEGFR at baseline in order to identify predictors of therapeutic response.
After completion of study treatment, patients are followed every 3 months for 2 years (from study entry), every 6 months for 3 years, and annually thereafter.
NOTE: Phase I completed. Investigator did not proceed with Phase II
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Erlotinib/RAD001 Ph I | Experimental | Drug: erlotinib, Drug: RAD001Tarceva (OSI-774; erlotinib) Everolimus (RAD001) Study did not progress to Phase II: Experimental: Erlotinib/RAD001 Phase II Maximum tolerated dose of erlotinib (Tarceva,OSI-774) and RAD001 (Everolimus) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Menopausal status not specified
- ECOG performance status 0-1
- Absolute neutrophil count ≥ 1,500/mm^3
- Platelet count ≥ 100,000/mm^3
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Key exclusion criteria (19 listed)
- Serious or non-healing active wound, ulcer, or bone fracture
- Known human immunodeficiency virus positivity
- Uncontrolled intercurrent illness including, but not limited to, any of the following
- More than 3 prior chemotherapy treatments in the metastatic setting
- Use of steroids or immunosuppressants
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 |
|---|---|---|
| erlotinibAlso: Tarceva (OSI-774)Levels: * 1 Erlotinib 50 mg/d * 2 Erlotinib 50 mg/d * 1 Erlotinib 100 mg/d * 2 Erlotinib 100 mg/d * 3 Erlotinib 150 mg/d * 4 Erlotinib 150 mg/d | Drug | Erlotinib/RAD001 Ph I |
| RAD001Also: everolimusLevels minus 1: RAD001 2.5 mg/d minus 2: RAD001 2.5 every other day 1. RAD001 2.5 mg per day 2. RAD001 5 mg per day 3. RAD001 10 mg per day 4. RAD001 10 mg per day | Drug | Erlotinib/RAD001 Ph I |
Primary outcome
To determine the maximum tolerated dose (MTD) of RAD001 given in combination with erlotinib (Phase I)
Time frame: at 4 weeks
MTD will be the dose level at which fewer than 2 of 6 (or 33% of) patients experience dose limiting toxicity (DLT), starting at first 4 weeks.
Anti-tumor activity of RAD001 in combination with erlotinib (Phase II)
Time frame: at 6 months
Clinical benefit based upon number of patients with complete response (CR), partial response (PR), and stable disease (SD). Responses are determined by Response Evaluation in Solid Tumors (RECIST)criteria v. 1.1: measurable lesions: complete response (CR) disappearance of target lesions, partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions
1 secondary outcome
Time to progression (Phase II)
Time frame: from study entry to disease progression
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 10 May 2016.
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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.
Ingrid Mayer, MD study chair
Vanderbilt-Ingram Cancer Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing erlotinib and RAD001 in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 3 sites 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 22 inclusion and 19 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 10 May 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites 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?
To determine the maximum tolerated dose (MTD) of RAD001 given in combination with erlotinib (Phase I) (time frame: at 4 weeks). The study lists 2 primary outcomes in all. 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 10 May 2016.