Breast CancerPhase 2NCT00573755
Sorafenib and Letrozole, Anastrozole, or Exemestane in Treating Postmenopausal Women With Estrogen Receptor-Positive and/or Progesterone Receptor-Positive Metastatic Breast Cancer
A Phase 2 study testing anastrozole, exemestane and letrozole in people with Breast Cancer, run by Mayo Clinic at 3 sites in United States.
Trial summary
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- anastrozole, exemestane and letrozole
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 4 participants
- Where
- 3 sitesUnited States
- Study dates
- Dec 2007to Apr 2013
- 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 to 120 years
- Women only
- No healthy volunteers
- Adult, Older adult
DISEASE CHARACTERISTICS:
- Histologically or cytologically confirmed adenocarcinoma of the breast
- Metastatic disease
- Measurable disease, defined as ≥ 1 unidimensionally measurable lesion ≥ 20 mm by conventional techniques (i.e., MRI or CT scan of chest, abdomen and pelvis) or ≥ 10 mm by spiral CT scan
- Non-measurable disease allowed, defined as all other lesions (or sites of disease), including small lesions (longest diameter < 20 mm by conventional techniques or < 10 mm by spiral CT scan)
- Must have objective evidence of progression within the past 3 months
- No human epidermal growth factor receptor 2 (HER2)/neu overexpression, defined as gene amplification by fluorescence in situ hybridization or 3+ overexpression by immunohistochemistry, or unknown HER2/neu status
- No active brain metastases
- Patients with neurological symptoms must undergo a contrast CT scan or MRI of the brain to exclude active brain metastasis
- Patients with treated brain metastases allowed provided they have no evidence of disease and have been off definitive therapy (including steroids) for the past 3 months
- Hormone receptor status:
- Estrogen receptor- and/or progesterone receptor-positive disease
PATIENT CHARACTERISTICS:
- Female
- The Eastern Cooperative Oncology Group (ECOG) performance status 0-1
- Postmenopausal
- Hemoglobin ≥ 9.0 g/dL
- ANC ≥ 1,500/mm³
- Platelet count ≥ 100,000/mm³
- Total bilirubin ≤ 1.5 times upper limit of normal (ULN)
- ALT and AST ≤ 2.5 times ULN (≤ 5 times ULN for patients with liver involvement)
- INR ≤ 1.5
- PTT within normal limits
- Creatinine ≤ 1.5 times ULN
- Not nursing, pregnant, or able to become pregnant
- No significant traumatic injury within the past 4 weeks
- No history of bleeding diathesis or uncontrolled coagulopathy
- No serious, nonhealing wound, ulcer, or bone fracture
- No clinically significant cardiac disease, including any of the following:
- New York Heart Association class III-IV congestive heart failure
- Unstable angina (i.e., anginal symptoms at rest) or new-onset angina (i.e., began within the past 3 months)
- Myocardial infarction within the past 6 months
- No cardiac ventricular arrhythmias requiring antiarrhythmic therapy
- No uncontrolled hypertension (systolic BP > 150 mm Hg or diastolic BP > 90 mm Hg), despite optimal medical management
- No thrombolic, embolic, venous, or arterial events (e.g., cerebrovascular accident including transient ischemic attacks) within the past 6 months
- No pulmonary hemorrhage or bleeding event > grade 2 within the past 4 weeks
- No other hemorrhage or bleeding event ≥ grade 3 within the past 4 weeks
- No active clinically serious infection > grade 2
- No known HIV infection
- No chronic hepatitis B or C infection
- No previous or concurrent cancer that is distinct in primary site or histology from breast cancer except carcinoma in situ of the cervix, treated basal cell skin cancer, superficial bladder tumors (i.e., Ta and Tis), or any cancer curatively treated within the past 5 years
- No known or suspected allergy to sorafenib tosylate or other agents used in this study
PRIOR CONCURRENT THERAPY:
- See Disease Characteristics
- No major surgery or open biopsy within the past 4 weeks
- No more than 1 prior regimen of endocrine therapy for metastatic breast cancer, provided that the patient has not received an aromatase inhibitor within the past 12 months
- No more than 1 prior regimen of chemotherapy for metastatic disease
- More than 2 weeks since prior radiotherapy, except if to a non-target lesion only or single-dose radiotherapy for palliation
- Prior radiotherapy to a target lesion(s) is permitted only if there has been clear progression of the lesion since radiotherapy was completed
- Concurrent anticoagulation treatment (e.g., warfarin or heparin) allowed
- No concurrent Hypericum perforatum (St. John's wort), rifampin, bevacizumab, or any other drugs (licensed or investigational) that target vascular endothelial growth factor (VEGF) or VEGF receptors
- No concurrent cytochrome P450 enzyme-inducing anti-epileptic drugs (e.g., phenytoin, carbamazepine, or phenobarbital)
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Mayo Clinic in Florida
Jacksonville, Florida, 32224
Mayo Clinic
Rochester, Minnesota, 55905
Mayo Clinic in Arizona
Scottsdale, Arizona, 55259
About this study
Official title: Phase II Randomized Study of Sorafenib Compared to Placebo When Administered in Combination With Aromatase Inhibitors for Postmenopausal Women With Metastatic Breast Cancer
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Aromatase inhibition therapy using letrozole, anastrozole, or exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether sorafenib is more effective than a placebo when given together with letrozole, anastrozole, or exemestane in treating metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying how well sorafenib works compared with a placebo when given together with letrozole, anastrozole, or exemestane in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive metastatic breast cancer.
Read the detailed description
OBJECTIVES:
Primary
- To compare the progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive metastatic breast cancer treated with sorafenib tosylate vs placebo and letrozole, anastrozole, or exemestane.
Secondary
- To compare the overall survival and time to treatment failure of patients treated with these regimens.
- To compare the objective tumor response rate and duration of response in patients treated with these regimens.
- To assess the adverse event profile of sorafenib tosylate in combination with aromatase inhibitors in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to prior aromatase inhibitor therapy (yes vs no) and line of endocrine therapy for metastatic disease (first-line vs second-line). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28.
- Arm II: Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically for up to 5 years.
- Conditions
- Breast Cancer
- Being tested
- anastrozole, exemestane, letrozole, sorafenib tosylate, placebo
- Keywords
- stage IV breast cancer, recurrent 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.
anastrozoleDrug
given orally
exemestaneDrug
given orally
letrozoleDrug
given orally
sorafenib tosylateDrug
given orally
placeboOther
given orally
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: anastrozole; Drug: exemestane; Drug: letrozole; Drug: sorafenib tosylate |
| Arm II | Active comparator | Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. Receives: Drug: anastrozole; Drug: exemestane; Drug: letrozole; Other: placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival
Progression-free survival was defined as the time from randomization to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment and then never return for any evaluations, the participant was censored for progression 1 day post-randomization.
Measured: Time from randomization to disease progression or death (up to 5 years)
Secondary outcomes (5)
Overall Survival
Survival time was defined as the time from randomization to death due to any cause.
Measured: Time from randomization to death (up to 5 years)
Time to Treatment Failure
Time to treatment failure was defined as the time from the date of the randomization to the date at which the patient was removed from treatment due to progression, adverse events, or refusal.
Measured: Time from randomization to treatment failure (up to 5 years)
Objective Tumor Response Rate
A confirm response was defined as either a complete response (CR) or partial response (PR) noted as the objective status on 2 consecutive evaluation at least 4 weeks apart. The confirmed response rate was estimated within each treatment group by the number of confirmed responses divided by the total number of participants randomized.
Measured: Up to 5 years
Duration of Response
Duration of response was defined for all patients who have achieved a confirmed response as the date at which the patient's earliest best objective status was first noted to be either a CR or PR to the earliest date progression was documented.
Measured: Up to 5 years
Adverse Event
Number of participants that experienced adverse events (grade 3 and above) as measured by NCI Common Terminology Criteria for Adverse Events (CTCAE) v3.0. Adverse events were assessed every week during first 6 weeks of therapy, every 4 weeks on months 1 to 6, every 12 weeks on months 7 and beyond and at the end of treatment.
Measured: Time from randomization to end of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Dec 2007 (estimated)
- Study startDec 2007
- Primary completionApr 2013
- Study completionApr 2013
Why it stopped: lack of participant 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 Mayo ClinicThe 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
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 4 participants (actual)
Sponsor and investigators
- Lead sponsor
- Mayo Clinic
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Vivek Roy, MD, Study chair, Mayo ClinicDonald W Northfelt, M.D., Principal investigator, Mayo ClinicTimothy J Hobday, M.D., Principal investigator, Mayo Clinic
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00573755
- Sponsor's protocol ID
- RC0731
- Other IDs
- P30CA015083, RC0731, 07-005768
- Status last verified
- Oct 2015
- First submitted
- 13 Dec 2007
- Last updated
- 5 Feb 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 5 Feb 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Randomized Study of Sorafenib Compared to Placebo When Administered in Combination With Aromatase Inhibitors for Postmenopausal Women With Metastatic Breast Cancer
- ClinicalTrials.gov ID
- NCT00573755
- Acronym / sponsor ID
- RC0731
- Conditions
- Breast Cancer
- Keywords
- stage IV breast cancer, recurrent breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of participant accrual
- Enrolment
- 4 participants (actual)
- Lead sponsor
- Mayo ClinicUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- Dec 2007
- Primary completion
- Apr 2013 (actual)
- Study completion
- Apr 2013 (actual)
- First posted
- 14 Dec 2007 (estimated)
- Results
- Posted 26 Mar 2014
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
RATIONALE: Sorafenib may stop the growth of tumor cells by blocking blood flow to the tumor and by blocking some of the enzymes needed for cell growth. Estrogen can cause the growth of breast cancer cells. Aromatase inhibition therapy using letrozole, anastrozole, or exemestane may fight breast cancer by lowering the amount of estrogen the body makes. It is not yet known whether sorafenib is more effective than a placebo when given together with letrozole, anastrozole, or exemestane in treating metastatic breast cancer.
PURPOSE: This randomized phase II trial is studying how well sorafenib works compared with a placebo when given together with letrozole, anastrozole, or exemestane in treating postmenopausal women with estrogen receptor-positive and/or progesterone receptor-positive metastatic breast cancer.
Detailed description
OBJECTIVES:
Primary
- To compare the progression-free survival of postmenopausal women with estrogen receptor- and/or progesterone receptor-positive metastatic breast cancer treated with sorafenib tosylate vs placebo and letrozole, anastrozole, or exemestane.
Secondary
- To compare the overall survival and time to treatment failure of patients treated with these regimens.
- To compare the objective tumor response rate and duration of response in patients treated with these regimens.
- To assess the adverse event profile of sorafenib tosylate in combination with aromatase inhibitors in these patients.
OUTLINE: This is a multicenter study. Patients are stratified according to prior aromatase inhibitor therapy (yes vs no) and line of endocrine therapy for metastatic disease (first-line vs second-line). Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28.
- Arm II: Patients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28.
In both arms, treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study therapy, patients are followed periodically for up to 5 years.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: anastrozole, Drug: exemestane, Drug: letrozole, Drug: sorafenib tosylatePatients receive oral sorafenib tosylate twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
| Arm II | Active comparator | Drug: anastrozole, Drug: exemestane, Drug: letrozole, Other: placeboPatients receive oral placebo twice daily and oral letrozole, anastrozole, or exemestane once daily on days 1-28. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 to 120 years
- 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 |
|---|---|---|
| anastrozolegiven orally | Drug | Arm I, Arm II |
| exemestanegiven orally | Drug | Arm I, Arm II |
| letrozolegiven orally | Drug | Arm I, Arm II |
| sorafenib tosylategiven orally | Drug | Arm I |
| placebogiven orally | Other | Arm II |
Primary outcome
Progression-free Survival
Time frame: Time from randomization to disease progression or death (up to 5 years)
Progression-free survival was defined as the time from randomization to the earliest date of documentation of disease progression or death due to any cause. In the case of a participant started treatment and then never return for any evaluations, the participant was censored for progression 1 day post-randomization.
5 secondary outcomes
Overall Survival
Time frame: Time from randomization to death (up to 5 years)
Time to Treatment Failure
Time frame: Time from randomization to treatment failure (up to 5 years)
Objective Tumor Response Rate
Time frame: Up to 5 years
Duration of Response
Time frame: Up to 5 years
Adverse Event
Time frame: Time from randomization to end of treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 5 Feb 2016.
- 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.
Vivek Roy, MD study chair
Mayo Clinic
Donald W Northfelt, M.D. principal investigator
Mayo Clinic
Timothy J Hobday, M.D. principal investigator
Mayo Clinic
3 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 anastrozole, exemestane and letrozole in people with Breast Cancer, run by Mayo Clinic 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?
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 5 Feb 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 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 Mar 2014). 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?
Progression-free Survival (time frame: Time from randomization to disease progression or death (up to 5 years)). 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 5 Feb 2016.