Breast CancerPhase 2NCT00462865
Trial of Chemotherapy and Avastin as Treatment for Women With Breast Cancer at High Risk for Relapse
A Phase 2 study testing Gemcitabine and Capecitabine and Avastin in people with Breast Cancer, run by Brown University at 3 sites in United States.
Trial summary
Women with breast cancer who are not eligible for breast conserving surgery or who have node-involvement are sometimes treated with chemotherapy up front, in hopes of allowing for a woman to keep her breast and decreasing the size of the excision for her breast cancer. Read more about this study
- Who is it for?
- Ages 18 to 80 years, women only
- Conditions the study is for
- Breast Cancer
- What is being tested?
- Gemcitabine and Capecitabine and Avastin
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 18 participants
- Where
- 3 sitesUnited States
- Study dates
- Nov 2007to Jan 2014
- 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 80 years
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- General health
- Women Age >18.
- ECOG Performance status 0-1
- Life expectancy must be 3 months. Clinical stage
- Histologically or cytologically adenocarcinoma of breast
- Pre-operative stage II-III per AJCC 6th edition, based on baseline evaluation by clinical examination, breast imaging, and/or preoperative work-up.
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- Evidence of residual invasive breast cancer or node positive disease following neoadjuvant chemotherapy.
- Prior Therapy
- Patients must have received primary (neoadjuvant) chemotherapy for local or locoregional breast cancer containing an anthracycline and a taxane.
- Patients must have completed definitive resection of primary tumor with adequate excision of gross disease.
- Patients must have residual invasive carcinoma in the breast and/or residual carcinoma in one or more regional nodes following preoperative chemotherapy.
- Adequate hematologic and metabolic parameters within four weeks of study entry defined as:
- Absolute neutrophil count ≥1,500/mm3 Platelets ≥ 150,000/mm3
- Total bilirubin ≤ 2.0 mg/dL
- Serum creatinine ≤ 2x upper limit of normal
- Serum calcium ≤1.5x upper normal limit Concurrent treatments
- Current use of anti-coagulants is allowed as long as patients have been on a stable dose for more than 2 weeks with stable INR.
- Chronic therapy with full dose aspirin up to 325 mg/day or standard non-steroidal anti-inflammatory agents is allowed.
- Informed consent
- Provision of signed informed consent.
Who cannot join
- Prior therapy
- No prior gemcitabine, continuous infusion 5-FU, or oral fluoropyrimidine (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.)
- No known hypersensitivity to capecitabine or prior unanticipated severe reaction to (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.) therapy or known hypersensitivity to 5-fluorouracil.
- No concurrent or prior endocrine therapy as adjuvant treatment.
- No prior breast radiation
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in another experimental drug study
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- Stage IV breast cancer
- Patients must not have evidence of metastatic disease at enrollment. Women of child-bearing potential.
- Nonpregnant and nonlactating.
- Women of child-bearing potential must have a negative serum pregnancy test and must agree to an effective means of contraception during the entire study period.
- Concurrent medical conditions:
- No other active cancers, except non-melanoma skin cancers.
- No serious infection or other serious underlying medical condition that would otherwise impair their ability to receive protocol treatment.
- Patients with clinically significant medical or psychiatric problems which may interfere with treatment on study.
- Avastin-specific exclusions:
- Inadequately controlled hypertension (defined as systolic blood pressure 150 and/or diastolic blood pressure > 100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Grade II or greater congestive heart failure
- Known CNS disease
- Significant vascular disease (e.g., aortic aneurysm, aortic dissection)
- Symptomatic peripheral vascular disease
- Evidence of bleeding diathesis or coagulopathy
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to study enrollment or anticipation of need for major surgical procedure during the course of the study
- Core biopsy or other minor surgical procedure, excluding placement of a vascular access device, within 7 days prior to study enrollment
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months prior to study enrollment
- Serious, non-healing wound, ulcer, or bone fracture
- Proteinuria at screening as demonstrated by urine dipstick for proteinuria ≥ 2+ (patients discovered to have ≥2+ proteinuria on dipstick urinalysis at baseline should undergo a 24 hour
- urine collection and must demonstrate ≤ 1g of protein in 24 hours to be eligible).
- Known hypersensitivity to any component of bevacizumab any history of stroke or transient ischemic attack at any time
- History of myocardial infarction or unstable angina within 12 months of study enrollment Inability to comply with study and/or follow-up procedures
Trial locations and contacts
3 sites in 1 country.
United States3 sites
University of New Mexico Cancer Center
Albuquerque, New Mexico, 87106
Lifespan Hospitals
Providence, Rhode Island, 02903
Women & Infants' Hospital
Providence, Rhode Island, 02905
About this study
Official title: A Phase II Study of Adjuvant Gemcitabine/Capecitabine and Bevacizumab for Patients Treated Neoadjuvantly Chemotherapy for Early Stage Breast Cancer With High Risk for Relapse
Women with breast cancer who are not eligible for breast conserving surgery or who have node-involvement are sometimes treated with chemotherapy up front, in hopes of allowing for a woman to keep her breast and decreasing the size of the excision for her breast cancer. While current research has shown that survival is the same whether women are treated with chemotherapy first or surgery first for breast cancer, the investigators do not yet know how to treat women with persistent breast cancer after she has received primary chemotherapy. This study looks at the use of a combination regimen of two agents (gemcitabine and capecitabine), both of which are active in breast cancer, and using Avastin to see if this regimen can be given to women treated with primary chemotherapy and then surgery, considered to be at high risk of relapse.
Read the detailed description
For patients with locally advanced breast cancers (LABC) primary or neoadjuvant chemotherapy (NAC) has become accepted as standard treatment. Advantages of NAC include shrinking the primary tumor, often rendering an unresectable cancer resectable, and the theoretically concurrent treatment of occult metastatic disease prior to definitive local therapy (surgery +/- radiation therapy). NAC can reduce the extent of surgery required for the management of local breast cancer from mastectomy to lump- or segmentectomy, without compromising major outcome measures, such as overall and disease free survival. At this time, the current standard of care for women felt to be candidates for NAC is an anthracycline + taxane regimen. The intent is to induce a pCR which as noted above is a strong indicator of survival. Yet, in both large NSABP studies, the proportion of women achieving this is less than 20% with these regimens raising a major challenge in clinical practice: what is the appropriate treatment for women with persistent disease after NAC? Given that gemcitabine and capecitabine are non-cross-resistant to anthracyclines and taxanes and use a different mechanism of action, have an acceptable toxicity profile, and in the absence of standard options for therapy we are interested in utilizing these agents coupled with bevacizumab as adjuvant treatment in women with residual breast cancer following primary chemotherapy.
- Conditions
- Breast Cancer
- Being tested
- Gemcitabine and Capecitabine and Avastin
- Keywords
- breast cancer, neoadjuvant chemotherapy, adjuvant treatment, consolidation therapy, anti-angiogenesis therapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Gemcitabine and Capecitabine and AvastinDrug
Also called Gemzar, Xeloda, Bevacizumab
avastin administered concurrently with chemotherapy (gemcitabine + capecitabine) for six cycles followed by single agent avastin to complete one year of treatment. Radiation therapy (if planned) will take place after adjuvant chemotherapy completes.
| Study group | Role | What they receive |
|---|---|---|
| Gemcitabine and Capecitabine and Avastin | Experimental | Avastin administered concurrently with chemotherapy (Gemcitabine + Capecitabine) for six cycles followed by single agent Avastin to complete one year of treatment. Radiation therapy (if planned) will take place after adjuvant chemotherapy completes. Receives: Drug: Gemcitabine and Capecitabine and Avastin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity Related to Treatment
6 out of 17 patients came off study for toxicity prior to receiving all treatment. Toxicity issues of administering 6 cycles of gemcitabine, capecitabine, and Avastin and one year of consolidation of Avastin in women with breast cancer previously treated with neoadjuvant chemotherapy that lead to patients being taken off study.
Measured: 1 year
Secondary outcomes (1)
Number of Participants With Recurrent Disease
Measured: 6 months and again at the end of the study (1 year)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted19 Apr 2007 (estimated)
- Study startNov 2007
- Primary completionMar 2012
- Study completionJan 2014
Why it stopped: DSMB determined toxicity of regimen more than originally thought. 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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Breast CancerStudies of the same condition, open and under way.
- More trials run by Brown 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
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 18 participants (actual)
Sponsor and investigators
- Lead sponsor
- Brown University
- Sponsor type
- University, hospital or other
- Collaborators
- Women and Infants Hospital of Rhode Island, Rhode Island Hospital, The Miriam Hospital, Memorial Hospital of Rhode Island, University of New Mexico Cancer Center
- Responsible party
- Principal investigator, Bachir Sakr, Brown University
- Investigators
- Bachir Sakr, MD, Principal investigator, Women & Infants' Hospital of Rhode IslandWilliam Sikov, MD, Principal investigator, Lifespan HospitalsMelanie Royce, MD, Principal investigator, University of New Mexico Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00462865
- Sponsor's protocol ID
- BrUOG BR-213
- Other IDs
- AVF4173s
- Status last verified
- Apr 2019
- First submitted
- 18 Apr 2007
- Last updated
- 9 Apr 2019
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Sikov WM, Theall KP, Seidler CW, Strenger RS, Fenton MA. Gemcitabine and capecitabine in metastatic breast cancer (MBC): A Brown University Oncology Group (BrUOG) Proc ASCO; 2005; Orlando, FL; 2005. p. 785.
Study at a glance
From the registry record, last updated by the sponsor on 9 Apr 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Adjuvant Gemcitabine/Capecitabine and Bevacizumab for Patients Treated Neoadjuvantly Chemotherapy for Early Stage Breast Cancer With High Risk for Relapse
- ClinicalTrials.gov ID
- NCT00462865
- Acronym / sponsor ID
- BrUOG BR-213
- Conditions
- Breast Cancer
- Keywords
- breast cancer, neoadjuvant chemotherapy, adjuvant treatment, consolidation therapy, anti-angiogenesis therapy
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: DSMB determined toxicity of regimen more than originally thought. Slow accrual.
- Enrolment
- 18 participants (actual)
- Lead sponsor
- Brown UniversityUniversity, hospital or other
- Collaborators
- Women and Infants Hospital of Rhode Island, Rhode Island Hospital, The Miriam Hospital, Memorial Hospital of Rhode Island, University of New Mexico Cancer Center
- Study start
- Nov 2007
- Primary completion
- Mar 2012 (actual)
- Study completion
- Jan 2014 (actual)
- First posted
- 19 Apr 2007 (estimated)
- Results
- Posted 8 Apr 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Women with breast cancer who are not eligible for breast conserving surgery or who have node-involvement are sometimes treated with chemotherapy up front, in hopes of allowing for a woman to keep her breast and decreasing the size of the excision for her breast cancer. While current research has shown that survival is the same whether women are treated with chemotherapy first or surgery first for breast cancer, the investigators do not yet know how to treat women with persistent breast cancer after she has received primary chemotherapy. This study looks at the use of a combination regimen of two agents (gemcitabine and capecitabine), both of which are active in breast cancer, and using Avastin to see if this regimen can be given to women treated with primary chemotherapy and then surgery, considered to be at high risk of relapse.
Detailed description
For patients with locally advanced breast cancers (LABC) primary or neoadjuvant chemotherapy (NAC) has become accepted as standard treatment. Advantages of NAC include shrinking the primary tumor, often rendering an unresectable cancer resectable, and the theoretically concurrent treatment of occult metastatic disease prior to definitive local therapy (surgery +/- radiation therapy). NAC can reduce the extent of surgery required for the management of local breast cancer from mastectomy to lump- or segmentectomy, without compromising major outcome measures, such as overall and disease free survival. At this time, the current standard of care for women felt to be candidates for NAC is an anthracycline + taxane regimen. The intent is to induce a pCR which as noted above is a strong indicator of survival. Yet, in both large NSABP studies, the proportion of women achieving this is less than 20% with these regimens raising a major challenge in clinical practice: what is the appropriate treatment for women with persistent disease after NAC? Given that gemcitabine and capecitabine are non-cross-resistant to anthracyclines and taxanes and use a different mechanism of action, have an acceptable toxicity profile, and in the absence of standard options for therapy we are interested in utilizing these agents coupled with bevacizumab as adjuvant treatment in women with residual breast cancer following primary chemotherapy.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Gemcitabine and Capecitabine and Avastin | Experimental | Drug: Gemcitabine and Capecitabine and AvastinAvastin administered concurrently with chemotherapy (Gemcitabine + Capecitabine) for six cycles followed by single agent Avastin to complete one year of treatment. Radiation therapy (if planned) will take place after adjuvant chemotherapy completes. |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (20 listed)
- General health
- Women Age >18.
- ECOG Performance status 0-1
- Life expectancy must be 3 months. Clinical stage
- Histologically or cytologically adenocarcinoma of breast
Key exclusion criteria (30 listed)
- Prior therapy
- No prior gemcitabine, continuous infusion 5-FU, or oral fluoropyrimidine (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.)
- No known hypersensitivity to capecitabine or prior unanticipated severe reaction to (capecitabine, UFT, S-1, 5-FU/eniluracil, etc.) therapy or known hypersensitivity to 5-fluorouracil.
- No concurrent or prior endocrine therapy as adjuvant treatment.
- No prior breast radiation
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 |
|---|---|---|
| Gemcitabine and Capecitabine and AvastinAlso: Gemzar, Xeloda, Bevacizumabavastin administered concurrently with chemotherapy (gemcitabine + capecitabine) for six cycles followed by single agent avastin to complete one year of treatment. Radiation therapy (if planned) will take place after adjuvant chemotherapy completes. | Drug | Gemcitabine and Capecitabine and Avastin |
Primary outcome
Toxicity Related to Treatment
Time frame: 1 year
6 out of 17 patients came off study for toxicity prior to receiving all treatment. Toxicity issues of administering 6 cycles of gemcitabine, capecitabine, and Avastin and one year of consolidation of Avastin in women with breast cancer previously treated with neoadjuvant chemotherapy that lead to patients being taken off study.
1 secondary outcome
Number of Participants With Recurrent Disease
Time frame: 6 months and again at the end of the study (1 year)
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Apr 2019.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- BackgroundSikov WM, Theall KP, Seidler CW, Strenger RS, Fenton MA. Gemcitabine and capecitabine in metastatic breast cancer (MBC): A Brown University Oncology Group (BrUOG) Proc ASCO; 2005; Orlando, FL; 2005. p. 785.
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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.
Bachir Sakr, MD principal investigator
Women & Infants' Hospital of Rhode Island
William Sikov, MD principal investigator
Lifespan Hospitals
Melanie Royce, MD principal investigator
University of New Mexico 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 2 study testing Gemcitabine and Capecitabine and Avastin in people with Breast Cancer, run by Brown University 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 20 inclusion and 30 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 9 Apr 2019. 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 8 Apr 2015). 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?
Toxicity Related to Treatment (time frame: 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00462865, which also lists 1 linked publication.
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 Apr 2019.