Estrogen Receptor-positive Breast CancerPhase 2NCT01394211
Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer
A Phase 2 study testing anastrozole, pazopanib hydrochloride and therapeutic conventional surgery in people with Estrogen Receptor-positive Breast Cancer and Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, run by University of Arizona at 1 site in United States.
Trial summary
This phase II trial studies how well giving pazopanib hydrochloride and anastrozole before surgery works in treating patients with stage II-III estrogen receptor-positive breast cancer. Pazopanib hydrochloride and anastrozole 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
- Conditions the study is for
- Estrogen Receptor-positive Breast Cancer, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Male Breast Cancer
- What is being tested?
- anastrozole, pazopanib hydrochloride and therapeutic conventional surgery
- Type of treatment
- Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 2 participants
- Where
- 1 siteUnited States
- Study dates
- 13 Jul 2011to 12 Apr 2012
- 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
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are within the protocol determined screening or baseline timeframes, and equivalent to the specifications in the protocol; also note, a written waiver/approval from the Investigator/Sponsor is still required
- Histologically confirmed diagnosis of estrogen receptor-positive (ER+), HER2 negative breast cancer, with clinical stage II or III disease
- Stage IIA T0-1 N1 M0, T2 N0 M0, OR
- Stage IIB T2 N1 M0, T3 N0 M0 OR
- Stage IIIA T0-2 N2 M0, T3 N1-2 M0, OR
- Stage IIIB T4 N0-2 M0
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- Eastern Cooperative Oncology Group (ECOG) performance status of 0-2
- No evidence of distant metastatic disease
- Baseline Oncotype DX score of 29 or lower; patients with known Oncotype DX recurrence score (RS) of 30 or greater are not eligible
- Absolute neutrophil count (ANC) >= 1.5 x 10^9/L
- Hemoglobina >= 10 g/dL (5.6 mmol/L); subjects may not have had a transfusion within 7 days of screening assessment
- Platelets >= 100 x 10^9/L
- Prothrombin time (PT) or international normalized ratio (INR) =< 1.2 x upper limit of normal (ULN); subjects receiving anticoagulant therapy are eligible if their INR is stable and within the recommended range for the desired level of anticoagulation
- Activated partial thromboplastin time (aPTT) =< 1.2 x ULN
- Total bilirubin =< 1.5 x ULN
- Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) =< 2.5 x ULN; concomitant elevations in bilirubin and AST/ALT above 1.0 x ULN is not permitted
- Serum creatinine =< 1.5 mg/dL (133 umol/L) or, if > 1.5 mg/dL: calculated creatinine clearance (CLCR) >= 50 mL/min
- Urine protein to creatinine ratio (UPC) < 1; if UPC >= 1, then a 24-hour urine protein must be assessed; subjects must have a 24-hour urine protein value < 1 g to be eligible
- A female is eligible to enter and participate in this study if she is:
- Is post-menopausal
- Subjects not using hormone replacement therapy (HRT) must have experienced total cessation of menses for >= 1 year and be greater than 45 years in age, OR, in questionable cases, have follicle stimulating hormone (FSH) value > 40 mIU/mL and an estradiol value < 40 pg/mL (< 140 pmol/L)
- Subjects using HRT must have experienced total cessation of menses for >= 1 year and be greater than 45 years of age OR have had documented evidence of menopause based on FSH and estradiol concentrations prior to initiation of HRT; patients will be required to be off of HRT for at least 2 weeks prior to initiating therapy
Who cannot join
- Prior malignancy; note: subjects who have had another malignancy and have been disease-free for >= 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
- Known distant metastases at any site; history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with risk of bleeding
- Inflammatory bowel disease (e.g. ulcerative colitis, Crohn's disease), or
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- Other gastrointestinal conditions with increased risk of perforation
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 28 days of registration to the study; clinically significant gastrointestinal abnormalities that may affect absorption of investigational product including, but not limited to:
- Malabsorption syndrome
- Major resection of the stomach or small bowel
- Presence of uncontrolled infection
- Corrected QT interval (QTc) > 480 msecs using Bazett's formula
- History of any one or more of the following cardiovascular conditions within 6 months of registration on the study:
- Cardiac angioplasty or stenting
- Myocardial infarction
- Unstable angina
- Coronary artery bypass graft surgery
- Symptomatic peripheral vascular disease
- Class III or IV congestive heart failure, as defined by the New York Heart Association (NYHA)
- Poorly controlled hypertension [defined as systolic blood pressure (SBP) of >= 140 mmHg or diastolic blood pressure (DBP) of >= 90 mm Hg]; note: initiation of adjustment of antihypertensive medication(s) is permitted prior to study entry
- History of cerebrovascular accident including transient ischemic attack (TIA), pulmonary embolism or untreated deep venous thrombosis (DVT) within the past 6 months of registration on the study; note: subjects with recent DVT who have been treated with therapeutic anti-coagulating agents for at least 6 weeks of registration to the study are eligible
- Prior major surgery or trauma within 28 days of registration on the study prior to first dose of study drug and/or presence of any non-healing wound, fracture, or ulcer (procedures such as catheter placement not considered to be major)
- Evidence of active bleeding or bleeding diathesis
- Hemoptysis within 8 weeks of registration to the study
- Any serious and/or unstable pre-existing medical, psychiatric, or other condition that could interfere with subject's safety, provision of informed consent, or compliance to study procedures
- Treatment with any of the following anti-cancer therapies for the current diagnosis of stage 2-3 estrogen positive breast carcinoma:
- Radiation therapy, surgery or tumor embolization within 14 days prior to first dose of pazopanib OR
- Chemotherapy, immunotherapy, biologic therapy, investigational therapy or hormonal therapy within 14 days or five half-lives of a drug (whichever is longer) prior to the first dose of pazopanib
- Any ongoing toxicity from prior anti-cancer therapy that is > Grade 1 and/or that is progressing in severity, except alopecia
- Concomitant anti-cancer therapies are not permitted
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to Pazopanib or Anastrozole used in the study
- Concomitant use of medications or substances that are inhibitors or inducers of strong CYP3A4 inhibitors are ineligible
- Concomitant: the concomitant use of strong CYP3A4 inhibitors (e.g. ketoconazole, ritonavir, clarithromycin) may increase pazopanib concentrations and should be avoided; if coadministration of a strong CYP3A4 inhibitor is warranted, reduce the dose of pazopanib to 400 mg; further dose reductions may be needed if adverse effects occur during therapy; this dose is predicted to adjust the pazopanib AUC to the range observed without inhibitors; however, there are no clinical data with this dose adjustment in patients receiving strong CYP3A4 inhibitors; grapefruit juice should be avoided as it inhibits CYP3A4 activity and may also increase plasma concentrations of pazopanib
- Concomitant strong CYP3A4 inducer: the concomitant use of strong CYP3A4 inducers (e.g. rifampin) may decrease pazopanib concentrations and should be avoided
Trial locations and contacts
1 site in 1 country.
About this study
This phase II trial studies how well giving pazopanib hydrochloride and anastrozole before surgery works in treating patients with stage II-III estrogen receptor-positive breast cancer. Pazopanib hydrochloride and anastrozole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pazopanib hydrochloride and anastrozole together before surgery may make the tumor smaller and reduce the amount of normal cells that have to be removed
Read the detailed description
OBJECTIVES:
- To determine the pathologic complete response (pCR) rate at surgery.
SECONDARY OBJECTIVES:
- To evaluate alternative measurements of anti-tumor activity: proportion of patients achieving sustained decrease in antigen KI-67 (ki-67) at 12 weeks of therapy with anastrozole plus pazopanib (pazopanib hydrochloride); proportion of patients achieving down-staging to a pathologic stage 0 or 1 at surgery.
II. To assess qualitative and quantitative toxicity of this combination, with special emphasis on the frequency of events grade 3 or greater, or the occurrence of unexpected toxicities.
OUTLINE:
Patients receive pazopanib hydrochloride* orally (PO) once daily (QD) and anastrozole PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients then undergo definitive surgery.
NOTE: *Pazopanib hydrochloride is stopped 7-14 days before surgery.
- Conditions
- Estrogen Receptor-positive Breast Cancer, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Male Breast Cancer, Recurrent Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
- Being tested
- anastrozole, pazopanib hydrochloride, therapeutic conventional surgery
- Medical subject headings
- Breast Neoplasms, Male, Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
anastrozoleDrug
Also called ANAS, Arimidex, ICI-D1033
Given PO
pazopanib hydrochlorideDrug
Also called GW786034, Votrient
Given PO
therapeutic conventional surgeryProcedure or surgery
Undergo definitive surgery
| Study group | Role | What they receive |
|---|---|---|
| Neoadjuvant enzyme inhibitor therapy | Experimental | Patients receive pazopanib hydrochloride* PO QD and anastrozole PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients then undergo therapeutic conventional surgery.
NOTE: *Pazopanib hydrochloride is stopped 7-14 days before definitive surgery. Receives: Drug: anastrozole; Drug: pazopanib hydrochloride; Procedure: therapeutic conventional surgery |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of pCR at Primary Site (T0) and Nodal Sites (T0N0)
Defined as no evidence of microscopic invasive tumor present. Determined by pathology. Estimated with an exact 95% confidence interval.
Measured: Six months from the initiation of neoadjuvant therapy
Secondary outcomes (2)
Proportion of Patients Achieving Sustained Decrease in Ki-67
Measured: 12 weeks from the initiation of neoadjuvant therapy
Proportion of Patients Achieving Down-staging to a Pathologic Stage 0 or 1
Measured: Six months from the initiation of neoadjuvant therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jul 2011 (estimated)
- Study start13 Jul 2011
- Primary completion12 Apr 2012
- Study completion12 Apr 2012
Why it stopped: Slow 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 Estrogen Receptor-positive Breast CancerStudies of the same condition, open and under way.
- More trials run by University of ArizonaThe 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
- Masking
- None (open label)
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Arizona
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI), GlaxoSmithKline
- Responsible party
- Sponsor
- Investigators
- Robert Livingston, Principal investigator, University of Arizona
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01394211
- Sponsor's protocol ID
- 11-0269-04
- Other IDs
- NCI-2011-01114, 3P30CA023074
- Status last verified
- Jul 2018
- First submitted
- 28 Jun 2011
- Last updated
- 26 Jul 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Jul 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Neo-adjuvant Therapy With Anastrozole Plus Pazopanib in Stage II and III ER+ Breast Cancer
- ClinicalTrials.gov ID
- NCT01394211
- Acronym / sponsor ID
- 11-0269-04
- Conditions
- Estrogen Receptor-positive Breast Cancer, Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, Male Breast Cancer, Recurrent Breast Cancer, Stage II Breast Cancer, Stage IIIA Breast Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Slow accrual
- Enrolment
- 2 participants (actual)
- Lead sponsor
- University of ArizonaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI), GlaxoSmithKline
- Study start
- 13 Jul 2011 (actual)
- Primary completion
- 12 Apr 2012 (actual)
- Study completion
- 12 Apr 2012 (actual)
- First posted
- 14 Jul 2011 (estimated)
- Results
- Posted 26 Jul 2018
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial studies how well giving pazopanib hydrochloride and anastrozole before surgery works in treating patients with stage II-III estrogen receptor-positive breast cancer. Pazopanib hydrochloride and anastrozole may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Giving pazopanib hydrochloride and anastrozole together before surgery may make the tumor smaller and reduce the amount of normal cells that have to be removed
Detailed description
OBJECTIVES:
- To determine the pathologic complete response (pCR) rate at surgery.
SECONDARY OBJECTIVES:
- To evaluate alternative measurements of anti-tumor activity: proportion of patients achieving sustained decrease in antigen KI-67 (ki-67) at 12 weeks of therapy with anastrozole plus pazopanib (pazopanib hydrochloride); proportion of patients achieving down-staging to a pathologic stage 0 or 1 at surgery.
II. To assess qualitative and quantitative toxicity of this combination, with special emphasis on the frequency of events grade 3 or greater, or the occurrence of unexpected toxicities.
OUTLINE:
Patients receive pazopanib hydrochloride* orally (PO) once daily (QD) and anastrozole PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients then undergo definitive surgery.
NOTE: *Pazopanib hydrochloride is stopped 7-14 days before surgery.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Neoadjuvant enzyme inhibitor therapy | Experimental | Drug: anastrozole, Drug: pazopanib hydrochloride, Procedure: therapeutic conventional surgeryPatients receive pazopanib hydrochloride* PO QD and anastrozole PO QD for 6 months in the absence of disease progression or unacceptable toxicity. Patients then undergo therapeutic conventional surgery. NOTE: *Pazopanib hydrochloride is stopped 7-14 days before definitive surgery. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (22 listed)
- Subjects must provide written informed consent prior to performance of study-specific procedures or assessments, and must be willing to comply with treatment and follow-up; procedures conducted as part of the subject's routine clinical management (e.g., blood count, imaging study) and obtained prior to signing of informed consent may be utilized for screening or baseline purposes provided these procedures are within the protocol determined screening or baseline timeframes, and equivalent to the specifications in the protocol; also note, a written waiver/approval from the Investigator/Sponsor is still required
- Histologically confirmed diagnosis of estrogen receptor-positive (ER+), HER2 negative breast cancer, with clinical stage II or III disease
- Stage IIA T0-1 N1 M0, T2 N0 M0, OR
- Stage IIB T2 N1 M0, T3 N0 M0 OR
- Stage IIIA T0-2 N2 M0, T3 N1-2 M0, OR
Key exclusion criteria (35 listed)
- Prior malignancy; note: subjects who have had another malignancy and have been disease-free for >= 5 years, or subjects with a history of completely resected non-melanomatous skin carcinoma or successfully treated in situ carcinoma are eligible
- Known distant metastases at any site; history or clinical evidence of central nervous system (CNS) metastases or leptomeningeal carcinomatosis
- Clinically significant gastrointestinal abnormalities that may increase the risk for gastrointestinal bleeding including, but not limited to:
- Active peptic ulcer disease
- Known intraluminal metastatic lesion/s with risk of bleeding
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 |
|---|---|---|
| anastrozoleAlso: ANAS, Arimidex, ICI-D1033Given PO | Drug | Neoadjuvant enzyme inhibitor therapy |
| pazopanib hydrochlorideAlso: GW786034, VotrientGiven PO | Drug | Neoadjuvant enzyme inhibitor therapy |
| therapeutic conventional surgeryUndergo definitive surgery | Procedure or surgery | Neoadjuvant enzyme inhibitor therapy |
Primary outcome
Rate of pCR at Primary Site (T0) and Nodal Sites (T0N0)
Time frame: Six months from the initiation of neoadjuvant therapy
Defined as no evidence of microscopic invasive tumor present. Determined by pathology. Estimated with an exact 95% confidence interval.
2 secondary outcomes
Proportion of Patients Achieving Sustained Decrease in Ki-67
Time frame: 12 weeks from the initiation of neoadjuvant therapy
Proportion of Patients Achieving Down-staging to a Pathologic Stage 0 or 1
Time frame: Six months from the initiation of neoadjuvant therapy
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Jul 2018.
- 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.
Robert Livingston principal investigator
University of Arizona
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 anastrozole, pazopanib hydrochloride and therapeutic conventional surgery in people with Estrogen Receptor-positive Breast Cancer and Human Epidermal Growth Factor 2 Negative Carcinoma of Breast, run by University of Arizona 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 22 inclusion and 35 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 26 Jul 2018. 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 26 Jul 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?
Rate of pCR at Primary Site (T0) and Nodal Sites (T0N0) (time frame: Six months from the initiation of neoadjuvant therapy). 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 26 Jul 2018.