Breast CancerPhase 2NCT00611715
Ph II Letrozole + OSI-774 (Tarceva) in Post-menopausal, w/ ER and/or PR-positive Met Breast Cancer.
A Phase 2 study testing erlotinib hydrochloride, letrozole and fluorescence in situ hybridization in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 9 sites in United States.
Trial summary
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- erlotinib hydrochloride, letrozole and fluorescence in situ hybridization
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 48 participants
- Where
- 9 sitesUnited States
- Study dates
- Nov 2003to Dec 2008
- 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
- Patients must have estrogen (ER) and/or progesterone receptor (PgR)-positive, histologically confirmed adenocarcinoma of the breast with measurable (but not operable) locally recurrent disease, or measurable and/or evaluable metastatic disease (see protocol section 10.3), including isolated bone metastases.
- Patients with available paraffin tissue blocks from either the primary or the metastatic site must submit tissue blocks for retrospective EGFR and HER2 analysis. If tissue blocks cannot be submitted, 20 unstained slides from each paraffin block must be submitted.
- All patients must be post-menopausal females as defined by one of the following:
- Prior bilateral oophorectomy
- Prior bilateral ovarian irradiation
- No menstrual period for 12 months or longer
- If age 55 years or less and < 12 months from last menstrual period, patient must have a serum estradiol < or equal to 30 and an FSH level > 40.
- Patients must not have had more than 1 prior chemotherapy regimen for metastatic disease and have fully recovered from any grade 2-4 toxicities related to chemotherapy. No concurrent chemotherapy is allowed while on protocol therapy.
- Patients may have had 1 prior hormonal therapy for metastatic disease. This includes: tamoxifen, fulvestrant, anastrozole, exemestane, aminoglutethimide, megace, and letrozole. Patients may have received tamoxifen or aromatase inhibitors in the adjuvant setting.
- Patients must not have had prior therapy with EGF receptor inhibitors.
- Previous but not concomitant therapy with trastuzumab (Herceptin) is allowed. Patients must not have received Herceptin within 4 weeks of initiation of protocol therapy.
- Patients must have an ECOG performance status of 0, 1, or 2.
- Patients must have adequate hematologic, hepatic, and renal function as defined by the following within 2 weeks of initiation of therapy:
- Absolute neutrophils > or equal to 1,500/mm3 and platelets > or equal to 100,000/mm3.
- Bilirubin < than or equal to 1.5 upper limit of normal.
- SGOT and SGPT < or equal to 2.5 upper limit of normal.
- Creatinine < or equal to 1.5 upper limit of normal.
- INR, PTT and PT in the normal range.
- Must be 18 years of age or older.
- Patients must not have a history of central nervous system metastases or unevaluated CNS symptoms suggestive of possible brain metastases.
- Patients may receive concurrent radiation therapy to painful bone metastases or areas of impending bone fracture as long as radiation therapy is initiated prior to study entry and sites of evaluable disease outside the radiation port(s) are available for follow-up. Patients who have received prior radiotherapy must have recovered from toxicity induced by this treatment.
- Patients < 55 years of age must not have received Luteinizing hormone releasing hormone (LHRH) antagonists within 3 months prior to protocol therapy.
- Patients must not suffer from medical or psychiatric conditions that would interfere with ability to provide informed consent, communicate side effects, or comply with protocol requirements including maintenance of a compliance/pill diary.
- Patients must be disease-free of prior invasive cancers for > 5 years with the exception of basal or squamous cancer of the skin or cervical carcinoma in situ.
Trial locations and contacts
9 sites in 1 country.
9 sites in 1 country
United States9 sites
Memorial Health Care System
Chattanooga, Tennessee, 37404
The Jones Clinic - Germantown
Germantown, Tennessee, 38138
Jennie Stuart Medical Center
Hopkinsville, Kentucky, 42240
Jackson-Madison County Hospital
Jackson, Tennessee, 38301
Tennessee Cancer Specialists
Knoxville, Tennessee, 37909
Central Georgia Hematology/Oncology Associates, P.C.
Macon, Georgia, 31201
Vanderbilt-Ingram Cancer Center - Cool Springs
Nashville, Tennessee, 37067
Vanderbilt-Ingram Cancer Center
Nashville, Tennessee, 37232-6838
Purchase Cancer Group
Paducah, Kentucky, 42002
About this study
Official title: A Phase II Trial of Letrozole Plus OSI-774 (Tarceva) in Post-menopausal Women With ER and/or PR-Positive Metastatic Breast Cancer
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with erlotinib may kill more tumor cells.
PURPOSE: This phase II clinical trial is studying how well giving letrozole together with erlotinib works in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally recurrent or metastatic breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- To determine the rate of clinical benefit (complete response [CR], partial response [PR], and stable disease [SD] in patients with hormone-dependent locally recurrent or metastatic breast cancer treated with letrozole in combination with erlotinib hydrochloride.
Secondary
- To determine the time to progression (TTP) in patients treated with this regimen.
- To evaluate the anti-tumor activity, as determined by CR and PR rates, of this regimen in these patients.
- To evaluate the safety of this regimen in these patients.
- To determine if tumors that are positive for epidermal growth factor receptor (EGFR) or Ser118 ER, or that overexpress human epidermal receptor (HER2) exhibit a longer TTP from the combination compared to tumors that do not express or overexpress these molecules.
OUTLINE: This is a multicenter study. Patients are stratified according to prior hormone therapy (hormone-therapy naive/first-line therapy vs prior hormonal therapy with either tamoxifen or an aromatase inhibitor in the adjuvant or metastatic setting/second-line therapy)
Patients receive oral letrozole and oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.
- Conditions
- Breast Cancer
- Being tested
- erlotinib hydrochloride, letrozole, fluorescence in situ hybridization, immunohistochemistry staining method, laboratory biomarker analysis
- Keywords
- recurrent breast cancer, stage IV breast cancer
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
erlotinib hydrochlorideDrug
Also called Tarceva, OSI-774
OSI-774 150 mg/day
letrozoleDrug
Also called Femara
Letrozole 2.5 mg/day
fluorescence in situ hybridizationGenetic
Also called None specified
To determine HER2 gene amplification or excess copies of the HER2 gene
immunohistochemistry staining methodOther
Also called None specified
to measure the epidermal growth factor receptors (EGFR)
laboratory biomarker analysisOther
Also called none specified
To determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs
| Study group | Role | What they receive |
|---|---|---|
| First line/hormone-therapy naive | Experimental | Not described Receives: Drug: erlotinib hydrochloride; Drug: letrozole; Genetic: fluorescence in situ hybridization; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis |
| Second-line/prev hormone-therapy tx | Experimental | Not described Receives: Drug: erlotinib hydrochloride; Drug: letrozole; Genetic: fluorescence in situ hybridization; Other: immunohistochemistry staining method; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Patients With Pathological Complete Response.
Per RECIST criteria v. 1.0: 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 24 weeks
Secondary outcomes (3)
Median Time to Progression of Target Lesions
Time frame from study entry till discontinuation of treatment due to disease progression. Progression of target lesions is measured by RECIST criteria v. 1.0: 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, progressive disease (PD) > 20% increase in the sum of the LD of target lesions or appearance of new lesions, stable disease (SD) neither sufficient decrease nor increase of the sum of smallest sum of the LD of target lesions.
Measured: Every 12 weeks from on-study to disease progression
Number of Patients With Anti-tumor Activity: Complete Response (CR) and Partial Response (PR)
Per RECIST criteria v. 1.0: measurable lesions: complete response (CR) disappearance of target lesions and partial response (PR) > 30% decrease in the sum of the longest diameter (LD) of target lesions.
Measured: at 24 weeks
Number of Patients With Worst-grade Toxicities Per Grade
Number of patients with worst-grade toxicities following NCI Common Toxicity Criteria: 1 = mild, 2 = moderate, 3 = severe, 4 = life-threatening, disabling, 5 = death
Measured: at 24 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Feb 2008 (estimated)
- Study startNov 2003
- Primary completionDec 2008
- Study completionDec 2008
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 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 2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 48 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
- NCT00611715
- Sponsor's protocol ID
- VICC BRE 0303
- Other IDs
- VU-VICC-BRE-0303, VU-VICC-030592, GENENTECH-VU-VICC-BRE-0303, NOVARTIS-VU-VICC-BRE-0303
- Status last verified
- Aug 2012
- First submitted
- 8 Feb 2008
- Last updated
- 9 Aug 2012
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Trial of Letrozole Plus OSI-774 (Tarceva) in Post-menopausal Women With ER and/or PR-Positive Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00611715
- Acronym / sponsor ID
- VICC BRE 0303
- Conditions
- Breast Cancer
- Keywords
- recurrent breast cancer, stage IV breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: low accrual
- Enrolment
- 48 participants (actual)
- Lead sponsor
- Vanderbilt-Ingram Cancer CenterUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Nov 2003
- Primary completion
- Dec 2008 (actual)
- Study completion
- Dec 2008 (actual)
- First posted
- 11 Feb 2008 (estimated)
- Results
- Posted 13 Jul 2012
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Estrogen can cause the growth of breast cancer cells. Hormone therapy using letrozole may fight breast cancer by blocking the use of estrogen by the tumor cells. Erlotinib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving letrozole together with erlotinib may kill more tumor cells.
PURPOSE: This phase II clinical trial is studying how well giving letrozole together with erlotinib works in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive locally recurrent or metastatic breast cancer.
Detailed description
OBJECTIVES:
Primary
- To determine the rate of clinical benefit (complete response [CR], partial response [PR], and stable disease [SD] in patients with hormone-dependent locally recurrent or metastatic breast cancer treated with letrozole in combination with erlotinib hydrochloride.
Secondary
- To determine the time to progression (TTP) in patients treated with this regimen.
- To evaluate the anti-tumor activity, as determined by CR and PR rates, of this regimen in these patients.
- To evaluate the safety of this regimen in these patients.
- To determine if tumors that are positive for epidermal growth factor receptor (EGFR) or Ser118 ER, or that overexpress human epidermal receptor (HER2) exhibit a longer TTP from the combination compared to tumors that do not express or overexpress these molecules.
OUTLINE: This is a multicenter study. Patients are stratified according to prior hormone therapy (hormone-therapy naive/first-line therapy vs prior hormonal therapy with either tamoxifen or an aromatase inhibitor in the adjuvant or metastatic setting/second-line therapy)
Patients receive oral letrozole and oral erlotinib hydrochloride once daily in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed every 3 months for 2 years, every 6 months for 3 years, and then yearly thereafter.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| First line/hormone-therapy naive | Experimental | Drug: erlotinib hydrochloride, Drug: letrozole, Genetic: fluorescence in situ hybridization, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis |
| Second-line/prev hormone-therapy tx | Experimental | Drug: erlotinib hydrochloride, Drug: letrozole, Genetic: fluorescence in situ hybridization, Other: immunohistochemistry staining method, Other: laboratory biomarker analysis |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
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 |
|---|---|---|
| erlotinib hydrochlorideAlso: Tarceva, OSI-774OSI-774 150 mg/day | Drug | First line/hormone-therapy naive, Second-line/prev hormone-therapy tx |
| letrozoleAlso: FemaraLetrozole 2.5 mg/day | Drug | First line/hormone-therapy naive, Second-line/prev hormone-therapy tx |
| fluorescence in situ hybridizationAlso: None specifiedTo determine HER2 gene amplification or excess copies of the HER2 gene | Genetic | First line/hormone-therapy naive, Second-line/prev hormone-therapy tx |
| immunohistochemistry staining methodAlso: None specifiedto measure the epidermal growth factor receptors (EGFR) | Other | First line/hormone-therapy naive, Second-line/prev hormone-therapy tx |
| laboratory biomarker analysisAlso: none specifiedTo determine if specific biomarkers exhibit a longer time to tumor progression after treatment with the study drugs | Other | First line/hormone-therapy naive, Second-line/prev hormone-therapy tx |
Primary outcome
Number of Patients With Pathological Complete Response.
Time frame: at 24 weeks
Per RECIST criteria v. 1.0: 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
3 secondary outcomes
Median Time to Progression of Target Lesions
Time frame: Every 12 weeks from on-study to disease progression
Number of Patients With Anti-tumor Activity: Complete Response (CR) and Partial Response (PR)
Time frame: at 24 weeks
Number of Patients With Worst-grade Toxicities Per Grade
Time frame: at 24 weeks
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2012.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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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
9 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing erlotinib hydrochloride, letrozole and fluorescence in situ hybridization in people with Breast Cancer, run by Vanderbilt-Ingram Cancer Center at 9 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?
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 9 Aug 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 9 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 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 13 Jul 2012). 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?
Number of Patients With Pathological Complete Response. (time frame: at 24 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 9 Aug 2012.