Breast CancerPhase 2NCT00481845
Phase 2 Anastrozole and Vandetanib (ZD6474) in Neoadjuvant Treatment of Postmenopausal Hormone Receptor-Positive Breast Cancer
A Phase 2 study testing Vandetanib and Anastrozole in people with Breast Cancer, run by Stanford University at 1 site in United States.
Trial summary
In this study we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2 with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. 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?
- Vandetanib and Anastrozole
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 1 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2008to Dec 2009
- 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
- Histologically confirmed invasive, hormone receptor-positive (ER and/or PR positive) breast cancer
- Stage I-III breast cancer including any primary tumor ≥ 1 cm by ultrasound
- Diagnosis by core needle biopsy with placement of metallic clip at tumor site
- Sentinel lymph node biopsy (US-guided FNA may be substituted if palpable axillary lymphadenopathy)
- Evaluation by a surgeon to determine eligibility for breast conservation
- Postmenopausal status (age ≥ 60 yo; or < 60 yo and FSH and estradiol in the postmenopausal range, prior bilateral oophorectomy)
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- Serum creatinine < 1.5 x upper limit of normal (ULN) or creatinine clearance > 50 mL/minute (calculated by Cockcroft-Gault formula.)
- Serum bilirubin < 1.5 x ULN
- Serum potassium ≥ 4 mmol/L (supplementation allowed)
- Serum calcium or magnesium within normal range (supplementation allowed)
- Alanine aminotransferase (ALT) or aspartate aminotransferase (AST) ≤ 2.5 x ULN or alkaline phosphatase (ALP) ≤ 2.5 x ULN
- ECOG Performance Status 0,1,2
- ECG QTc < 480 msec
- Measurable disease
- Written, informed consent
Who cannot join
- Metastatic breast cancer excluding disease in regional lymph nodes
- Inoperable disease considered irreversible with neoadjuvant endocrine therapy
- HER2-overexpressed breast cancer
- Prior chemotherapy or radiotherapy for the treatment of the current breast cancer
- Prior hormonal therapy for the treatment of the current breast cancer
- Prior surgical biopsy, lumpectomy, mastectomy for the current breast cancer
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- Any concurrent condition which in the Investigator's opinion makes it inappropriate for the patient to participate in the trial or which would jeopardize compliance with the protocol
- Currently active diarrhea that may affect the ability of the patient to absorb ZD6474 or tolerate diarrhea
- Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease >2 within 3 months before entry; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
- History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia (VT) or uncontrolled atrial fibrillation) which is symptomatic or requires treatment (CTCAE grade 3) or asymptomatic sustained VT. Atrial fibrillation controlled on medication is not excluded.
- Previous history of QTc prolongation as a result of another medication that required discontinuation of that medication.
- Congenital long QT syndrome or 1st degree relative with unexplained sudden death < 40 years of age.
- Presence of left bundle branch block (LBBB).
- QTc with Bazett's correction that is unmeasurable, or ≥ 480 msec on screening ECG. If a patient has QTc ≥ 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be < 480 msec in order for the patient to be eligible for the study.
- Use of any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function.
- Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm hg).
- Previous or current malignancies of other histologies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin.
- Major surgery within 4 weeks or incompletely healed surgical incision before starting study therapy.
- Receipt of any investigational agents within 30 days prior to commencing study treatment
- Previous enrollment or randomization of treatment in the present study
Trial locations and contacts
1 site in 1 country.
United States1 site
Stanford University School of Medicine
Stanford, California, 94305
About this study
Official title: Randomized Phase 2 Trial of Anastrozole Combined With Novel Agent ZD6474 in the Neoadjuvant Treatment of Postmenopausal Patients With Hormone Receptor-Positive Breast Cancer
In this study we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2 with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. The aim is to overcome mechanisms of resistance and simultaneously block multiple critical signaling pathways known to stimulate breast cancer.
Read the detailed description
The use of adjuvant chemotherapy and endocrine therapy has had a significant impact on breast cancer survival. However, not all patients will benefit from each of these therapies. Increasing data suggests that patients with hormone receptor-positive breast cancer derive marginal benefit from the addition of adjuvant chemotherapy. Identification and characterization of cellular signaling pathways active in the pathogenesis of breast cancer has lead to the development of multiple targeted therapies that hold enormous promise for patients with less toxicity than conventional chemotherapy. Treatment strategies employing neoadjuvant therapy have found that pCR is predictive for ultimate outcome. Due to this, the use of neoadjuvant therapy has become an intense area of investigation in operable breast cancer. In the IMPACT trial, the aromatase inhibitor anastrozole was found to improve eligibility for breast conservation and was associated with a favorable clinical objective response after 12 weeks of therapy.
In this proposed study, we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2, with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. The aim is to overcome mechanisms of resistance and simultaneously block multiple critical signaling pathways known to stimulate breast cancer. The two agents have non-overlapping toxicities and are both administered orally, allowing for a more tolerable treatment regimen. By using this combination in the neoadjuvant setting, we will target the critical signaling pathways early and follow tumor responses during therapy, allowing for prompt evaluation of the effectiveness of this treatment strategy. Pathologic tumor specimens obtained at the time of definitive surgery will be evaluated for pathologic complete response thus adding to the body of literature. By examining molecular markers such as ER, PR, EGFR, and Ki-67 pre- and post-treatment, we hope to correlate modulations in these biomarkers to response. Finally, using a novel second generation functional breast MRI we will investigate the ability of MRI to predict response to antiangiogenic therapy.
- Conditions
- Breast Cancer
- Being tested
- Vandetanib, Anastrozole
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VandetanibDrug
Also called Zactima, ZD6474
300 mg daily
AnastrozoleDrug
Also called Arimidex
1 mg daily
| Study group | Role | What they receive |
|---|---|---|
| Vandetanib + Anastrozole | Experimental | Vandetanib and Anastrozole as neoadjuvant therapy Receives: Drug: Vandetanib; Drug: Anastrozole |
| Anastrozole | Active comparator | Anastrozole as neoadjuvant therapy Receives: Drug: Anastrozole |
What is being measured
The primary outcome is the main question the study is designed to answer.
Tumor Objective Response by MRI
Determine tumor objective response rate by MRI. (CR): Disappearance of the target lesion (PR): At least a 30% decrease in the longest diameter of the target lesion taking as reference the baseline LD (PD): At least a 20% increase in the LD of target lesion, taking as reference the baseline LD or the appearance of one or more new lesions (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the baseline LD.
Measured: 1 year
Secondary outcomes (1)
Pathologic Complete Response
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Jun 2007 (estimated)
- Study startJan 2008
- Primary completionDec 2009
- Study completionDec 2009
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.
- More trials run by Stanford 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- AstraZeneca
- Responsible party
- Principal investigator, Mark Pegram, Stanford University
- Investigators
- Mark D Pegram, MD, Principal investigator, Stanford Cancer Institute, Stanford University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00481845
- Sponsor's protocol ID
- IRB-08051
- Other IDs
- BRSADJ0008, 97923
- Status last verified
- Dec 2016
- First submitted
- 31 May 2007
- Last updated
- 7 Feb 2017
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Randomized Phase 2 Trial of Anastrozole Combined With Novel Agent ZD6474 in the Neoadjuvant Treatment of Postmenopausal Patients With Hormone Receptor-Positive Breast Cancer
- ClinicalTrials.gov ID
- NCT00481845
- Acronym / sponsor ID
- IRB-08051
- Conditions
- Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 1 participants (actual)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- AstraZeneca
- Study start
- Jan 2008
- Primary completion
- Dec 2009 (actual)
- Study completion
- Dec 2009 (actual)
- First posted
- 4 Jun 2007 (estimated)
- Results
- Posted 7 Feb 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In this study we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2 with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. The aim is to overcome mechanisms of resistance and simultaneously block multiple critical signaling pathways known to stimulate breast cancer.
Detailed description
The use of adjuvant chemotherapy and endocrine therapy has had a significant impact on breast cancer survival. However, not all patients will benefit from each of these therapies. Increasing data suggests that patients with hormone receptor-positive breast cancer derive marginal benefit from the addition of adjuvant chemotherapy. Identification and characterization of cellular signaling pathways active in the pathogenesis of breast cancer has lead to the development of multiple targeted therapies that hold enormous promise for patients with less toxicity than conventional chemotherapy. Treatment strategies employing neoadjuvant therapy have found that pCR is predictive for ultimate outcome. Due to this, the use of neoadjuvant therapy has become an intense area of investigation in operable breast cancer. In the IMPACT trial, the aromatase inhibitor anastrozole was found to improve eligibility for breast conservation and was associated with a favorable clinical objective response after 12 weeks of therapy.
In this proposed study, we plan to study the combination of ZD6474, a dual inhibitor of EGFR and VEGFR-2, with anastrozole in the neoadjuvant setting for patients with Stage I-III breast cancer. The aim is to overcome mechanisms of resistance and simultaneously block multiple critical signaling pathways known to stimulate breast cancer. The two agents have non-overlapping toxicities and are both administered orally, allowing for a more tolerable treatment regimen. By using this combination in the neoadjuvant setting, we will target the critical signaling pathways early and follow tumor responses during therapy, allowing for prompt evaluation of the effectiveness of this treatment strategy. Pathologic tumor specimens obtained at the time of definitive surgery will be evaluated for pathologic complete response thus adding to the body of literature. By examining molecular markers such as ER, PR, EGFR, and Ki-67 pre- and post-treatment, we hope to correlate modulations in these biomarkers to response. Finally, using a novel second generation functional breast MRI we will investigate the ability of MRI to predict response to antiangiogenic therapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Vandetanib + Anastrozole | Experimental | Drug: Vandetanib, Drug: AnastrozoleVandetanib and Anastrozole as neoadjuvant therapy |
| Anastrozole | Active comparator | Drug: AnastrozoleAnastrozole as neoadjuvant therapy |
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)
- Histologically confirmed invasive, hormone receptor-positive (ER and/or PR positive) breast cancer
- Stage I-III breast cancer including any primary tumor ≥ 1 cm by ultrasound
- Diagnosis by core needle biopsy with placement of metallic clip at tumor site
- Sentinel lymph node biopsy (US-guided FNA may be substituted if palpable axillary lymphadenopathy)
- Evaluation by a surgeon to determine eligibility for breast conservation
Key exclusion criteria (20 listed)
- Metastatic breast cancer excluding disease in regional lymph nodes
- Inoperable disease considered irreversible with neoadjuvant endocrine therapy
- HER2-overexpressed breast cancer
- Prior chemotherapy or radiotherapy for the treatment of the current breast cancer
- Prior hormonal therapy for the treatment of the current breast cancer
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 |
|---|---|---|
| VandetanibAlso: Zactima, ZD6474300 mg daily | Drug | Vandetanib + Anastrozole |
| AnastrozoleAlso: Arimidex1 mg daily | Drug | Anastrozole, Vandetanib + Anastrozole |
Primary outcome
Tumor Objective Response by MRI
Time frame: 1 year
Determine tumor objective response rate by MRI. (CR): Disappearance of the target lesion (PR): At least a 30% decrease in the longest diameter of the target lesion taking as reference the baseline LD (PD): At least a 20% increase in the LD of target lesion, taking as reference the baseline LD or the appearance of one or more new lesions (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the baseline LD.
1 secondary outcome
Pathologic Complete Response
Time frame: 1 year
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2017.
- 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.
Mark D Pegram, MD principal investigator
Stanford Cancer Institute, Stanford University Medical 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 Vandetanib and Anastrozole in people with Breast Cancer, run by Stanford 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 15 inclusion and 20 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 7 Feb 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 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 7 Feb 2017). 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?
Tumor Objective Response by MRI (time frame: 1 year). 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 7 Feb 2017.