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Breast CancerPhase 2ABCDENCT00925652

Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer

A Phase 2 study testing Bevacizumab, Cyclophosphamide and Methotrexate in people with Breast Cancer, run by Dana-Farber Cancer Institute at 9 sites in United States.

Terminated

Stopped early. The study ended before it was planned to and will not resume.

Official record
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Trial summary

If residual breast cancer is found in the breast or lymph node tissue removed after preoperative chemotherapy, one may be at increased risk of breast cancer recurrence in the future. Read more about this study

Who is it for?
Ages 18 years and older
Conditions the study is for
Breast Cancer
What is being tested?
Bevacizumab, Cyclophosphamide and Methotrexate
Could I receive a placebo?
No, everyone receives an active treatment
How many people
55 participants
Where
9 sitesUnited States
Study dates
Sep 2010to 30 Jan 2019
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

  • Histologically or cytologically confirmed invasive breast cancer. HER2 positive disease is not allowed. Metastatic breast cancer (Stage IV) is not allowed.
  • For patients entering the trial after neoadjuvant chemotherapy, there must be the presence of residual invasive disease on pathologic review following neoadjuvant chemotherapy. Residual disease is defined as a Miller-Payne response in the breast of 0-4 and/or residual carcinoma in one or more regional lymph nodes that would meet AJCC 7th edition criteria for N1 - N3 disease. The presence of DCIS without invasion does not qualify as residual disease. Alternatively, if Miller-Payne grading is not available, the patient will be eligible if the pathology report indicates any residual invasive carcinoma following neoadjuvant therapy.
  • If tumor is triple negative (ER-/PR-/HER2-) and the patient received neoadjuvant chemotherapy, disease may be clinical stage I-III pre-operatively, per AJCC 7th edition, based on baseline evaluation by clinical examination and/or breast imaging. Patients must have the presence of residual invasive disease on pathologic review following their neoadjuvant chemotherapy.
  • If tumor is triple negative and the patient did not receive neoadjuvant chemotherapy, there must be pathologic lymph node positivity and Stage IIB or greater disease after surgery. For the purposes of eligibility, lymph node positivity can refer to either axillary or intramammary lymph nodes.
  • If tumor is hormone receptor positive, disease must be clinical Stage III neoadjuvantly, per AJCC 7th edition, based on baseline evaluation by clinical examination and/or breast imaging, or pathologic Stage IIB or greater at time of definitive surgery. Patients with hormone receptor positive breast cancer who do not receive neoadjuvant chemotherapy are not eligible for this protocol.
  • For patients who completed neoadjuvant chemotherapy, the regimen must contain an anthracycline, a taxane, or both. Patients who have received neoadjuvant therapy as part of a clinical trial are acceptable. Protocol therapy must be initiated < 180 days after last surgery for breast cancer. For triple negative patients who receive adjuvant chemotherapy only, the regimen must contain both an anthracycline and a taxane. For these patients, protocol therapy must be initiated < 28 weeks after initiation of adjuvant chemotherapy.
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  • Patients with ER+ and/or PR+ breast cancer should receive adjuvant hormonal therapy
  • No prior exposure to bevacizumab or other inhibitors of angiogenesis is allowed.
  • Patients must have completed definitive resection of primary tumor. Negative margins for both invasive and ductal carcinoma in situ (DCIS) are desirable, however positive margins are acceptable if the treatment team believes no further surgery is possible and patient has received radiotherapy. Patients with margins positive for lobular carcinoma in situ are eligible.
  • Post-mastectomy radiotherapy is suggested for all patients with a primary tumor 5cm or greater or involvement of 4 or more lymph nodes. Whole breast radiotherapy is required for patients who underwent breast conserving therapy, including lumpectomy, partial mastectomy, and excisional biopsy.
  • Patients must have the presence of residual invasive disease on pathologic review following their preoperative chemotherapy. The presence of DCIS without invasion does not qualify as residual disease. Alternatively, if Miller-Payne grading is not available, the patient will be eligible if the pathology report indicates any residual invasive carcinoma following preoperative therapy.
  • LVEF equal to or greater than institutional limits of normal after preoperative chemotherapy, as assessed by echocardiogram, within 30 days prior to registration
  • ECOG Performance Status 0-1 within 2 weeks of registration
  • 18 years of age or greater

Who cannot join

  • Laboratory assessments as outlined in the protocol
  • Stage IV breast cancer. Patients with metastatic disease are ineligible. However, specific staging studies are not required in the absence of symptoms
  • Prior history of hypertensive crisis or hypertensive encephalopathy
  • History if myocardial infarction or unstable angina within 12 months prior to registration
  • History of stroke or transient ischemic attack at any time
  • Significant vascular disease within 6 months prior to registration
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  • History of hemoptysis within 1 month prior to registration
  • Ongoing or active infection
  • NYHA Grade II or greater congestive heart failure
  • Unstable angina pectoralis
  • Psychiatric illness/social situations that would limit compliance with study requirements
  • Evidence of bleeding diathesis or significant coagulopathy
  • Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to registration 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 registration
  • History of abdominal fistula or gastrointestinal perforation within 6 months prior to registration
  • Serious, non-healing wound, active ulcer, or unhealed bone fracture
  • Known hypersensitivity to any component of bevacizumab or compounds of similar chemical or biologic composition to cyclophosphamide or methotrexate
  • Known HIV infection, as immunosuppression could be worsened by use of cyclophosphamide and methotrexate, and the impact of chemotherapy and/or bevacizumab therapy on the pharmacology of standard anti-HIV therapy is not known
  • Patient may not be pregnant, expect to become pregnant, plan to conceive a child while on study or breastfeeding.
  • Prior history of any malignancy treated without curative intent, or treated with curative intent within the past 5 years. Prior history of DCIS > 5 years before current breast cancer diagnosis is acceptable if ipsilateral (and no radiotherapy given) or contralateral (with or without radiotherapy) or contralateral (with or without radiotherapy). Prior history of contralateral stage 1 breast cancer > 5 years prior to the current breast cancer diagnosis is acceptable, however prior ER/PR+ breast cancer > stage 1 at any time is not allowed.
  • Patients with a pleural effusion or abdominal ascites are excluded because of the theoretical risk for methotrexate accumulation and related toxicity
  • Current use of anticoagulants is allowed as long as patients have been on a stable dose for more than two weeks with stable INR
  • Chronic therapy with full dose aspirin or standard non-steroidal anti-inflammatory agents is allowed
  • While on study, patients may not receive other investigational agents as part of other clinical trials
  • Adjuvant bisphosphonate use, on or off of clinical trial, is allowed. Patients may be started on adjuvant bisphosphonate therapy either before or after ABCDE trial enrollment

Trial locations and contacts

9 sites in 1 country.

9 sites in 1 country

United States9 sites

  • University of Alabama at Birmingham

    Birmingham, Alabama, 35294

  • Faulkner Hospital

    Boston, Massachusetts, 02130

  • Dana-Farber Cancer Institute

    Boston, Massachusetts, 02215

  • University of North Carolina Lineberger Comprehensive Cancer Center

    Chapel Hill, North Carolina, 27599

  • Duke University Medical Center

    Durham, North Carolina, 27710

  • Indiana Unversity Simon Cancer Center

    Indianapolis, Indiana, 46202

  • Dana-Farber/Brigham and Women's Cancer Center at Milford Regional Medical Center

    Milford, Massachusetts, 01757

  • Vanderbilt-Ingram Cancer Center

    Nashville, Tennessee, 37232

  • Memorial Sloan Kettering Cancer Center

    New York, New York, 10065

Other trials in United States

About this study

Official title: ABCDE: A Phase II Randomized Study of Adjuvant Bevacizumab, Metronomic Chemotherapy (CM), Diet and Exercise After Preoperative Chemotherapy for Breast Cancer

If residual breast cancer is found in the breast or lymph node tissue removed after preoperative chemotherapy, one may be at increased risk of breast cancer recurrence in the future. The purpose of this research study is to determine if having additional treatment after preoperative chemotherapy and surgery with bevacizumab and metronomic chemotherapy would make a difference in reducing the participants chance of breast cancer recurrence compared to the standard of care, which is observation alone. This study will also evaluate the potential additional benefits from participating in an exercise and dietary intervention compared to the dietary intervention alone. Because no one knows which which post-neoadjuvant strategy is best, participants will be "randomized" to one of the study groups: 1. Diet Intervention arm, 2. Diet and Exercise Intervention Arm, 3. Bevacizumab, cyclophosphamide, methotrexate and diet intervention, 4. Bevacizumab, cyclophosphamide, methotrexate, diet and exercise intervention arm.

Read the detailed description

Bevacizumab is an antibody that is made in the laboratory. Bevacizumab works differently from the way chemotherapy drugs work. Bevacizumab works to slow or stop the growth of cells in cancer tumors by decreasing the blood supply to tumors. Bevacizumab has been approved by the U.S Food and Drug Administration to treat advanced colorectal, lung and kidney cancers. Metronomic chemotherapy also attacks tumor blood supply. Standard chemotherapy drugs are used, cyclophosphamide and methotrexate (CM), but in very small daily doses by mouth, well below the threshold where they can cause people to feel sick. Previous research studies have shown that women with breast cancer who take metronomic CM and bevacizumab feel very well, and the combination therapy is active in reducing their cancer. Participants in this study will also be provided with diet or diet and exercise counseling over the telephone. Studies have shown that many women who are treated for breast cancer will gain weight during and after their treatment, and may also experience fatigue and weakness. Many studies have shown that making changes in diet and increasing exercise can help prevent weight gain and also may increase energy and decrease other side effects of chemotherapy and other breast cancer treatments.

Conditions
Breast Cancer
Being tested
Bevacizumab, Cyclophosphamide, Methotrexate, Lifestyle: Diet, Lifestyle: Diet+Exercise
Keywords
CM, bevacizumab, cyclophosphamide, methotrexate, exercise intervention, diet intervention
Medical subject headings
Breast Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

Study groups in NCT00925652
Study groupRoleWhat they receive
Lifestyle: DietExperimentalThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.
Receives: Behavioral: Lifestyle: Diet
Lifestyle: Diet+ExericiseExperimentalThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor.
Receives: Behavioral: Lifestyle: Diet; Behavioral: Lifestyle: Diet+Exercise
Lifestyle: Diet and Bevicizumab+CMExperimentalThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months
Receives: Drug: Bevacizumab; Drug: Cyclophosphamide; Drug: Methotrexate; Behavioral: Lifestyle: Diet
Lifestyle: Diet+Exericise and Bevicizumab+CMExperimentalThe dietary intervention focuses on the Food Pyramid, emphasizing diet that is low in fat and high in fruits, vegetables and fiber. The exercise intervention is comprised of a target physical activity goal of 180 minutes of moderate-intensity activity each week. Patients receive a series of 13 telephone calls over the course of one-year with a dedicated and trained counselor. Bevicizumab: 15 mg/kg administered intravenously day 1 of a 3-week cycle for 6 months and day 1 of a 6 week cycle up to 2 years Cyclophosphamide: 50 mg orally each day of a 3-week cycle for 6 months Methotrexate: 2.5 mg orally twice daily of a 3-week cycle for 6 months
Receives: Drug: Bevacizumab; Drug: Cyclophosphamide; Drug: Methotrexate; Behavioral: Lifestyle: Diet; Behavioral: Lifestyle: Diet+Exercise

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Median 3-year Recurrence-free Survival (RFS)

    RFS events is defined as the duration of time from randomization to time of an RFS event, marked as positive if any of listed event shows: local failure (invasive), regional failure, distant failure, contralateral breast cancer (invasive), any other second cancer (excluding non-melanomatous skin cancer or cervical cancer in situ), or death from any cause. The diagnosis of local or distant recurrence should be pathologically confirmed however if biopsy if not possible, radiology confirmation acceptable.

    Measured: Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.

Secondary outcomes (10)

  1. Feasibility Rate

    The feasibility of post-adjuvant maintenance metronomic chemotherapy is open to women with hormone receptor negative tumors and either node negative or node positive disease.

    Measured: 2 years

  2. Number of Serious Adverse Event of Bevacizumab

    Adverse event evaluations will occur at each study visit throughout the treatment period of 2 years and will continue every 6 months during the follow-up period. Only Grade 3/4 AE (CTCAE v4) was reported.

    Measured: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.

  3. Number of Serious Adverse Event of Metronomic Chemotherapy

    Adverse event evaluations will occur at each study visit throughout the treatment period of 2 years and will continue every 6 months during the follow-up period. Only Grade 3/4 AE (CTCAE v4) was reported.

    Measured: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.

  4. Number of Serious Adverse Event (AE) of Lifestyle

    Exercise and/or dietary lifestyle interventions defined per protocol. The lifestyle intervention will be administered by telephone, supplemented with a participant workbook (Appendix 9 in protocol). Only Grade 3/4 AE (CTCAE v4) was reported.

    Measured: Followed every 6 months for 7.5 years after study entry, or completion of final analysis, whichever comes first.

  5. Change in Level of Fasting Insulin

    Change in level of fasting insulin from baseline at study entry to 6 months.

    Measured: Baseline and 6 months

  6. Change in Body Weight

    data not collected due to early termination of the study.

    Measured: Baseline and 6 months

  7. Change in IGF-1

    Change in level of insulin-like growth factor -1 (IGF-1) from baseline at study entry to 6 months.

    Measured: Baseline and 6 months

  8. Changes in Diet and Physical Activity Upon Biomarkers

    To evaluate the impact of changes in diet and physical activity upon biomarkers associated with breast cancer risk and prognosis, including leptin, adiponectin, testosterone, estradiol and inflammatory mediators (including: TNF alpha, IL-1 beta, IL-2, IL-5, IL-6, IL-8, IL-10, and IL-12)

    Measured: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon biomarkers

  9. Changes in Physical Activity and Dietary Behaviors

    Measured: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon physical activity

  10. Impact Upon Anthropometric Measures, Quality of Life and Fatigue

    Measured: Participants will undergo a series of measures at baseline and 6- and 12-months after study enrollment to assess the impact of the telephone-based lifestyle interventions upon physical activity

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted22 Jun 2009 (estimated)
  2. Study startSep 2010
  3. Primary completion30 Jan 2015
  4. Study completion30 Jan 2019

Why it stopped: The study was terminated early due to slow accrual.

Resources

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
55 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT00925652
Sponsor's protocol ID
09-134
Other IDs
AVF 4571s; TBCRC 012
Acronym
ABCDE
Status last verified
Dec 2021
First submitted
19 Jun 2009
Last updated
19 Jan 2022
Data monitoring committee
Yes
Individual data sharing
No

Publications

  • Trapani D, Jin Q, Miller KD, Rugo HS, Reeder-Hayes KE, Traina T, Abdou Y, Falkson C, Abramson V, Ligibel J, Chen W, Come S, Nohria A, Ryabin N, Tayob N, Tolaney SM, Burstein HJ, Mayer EL. Optimizing Postneoadjuvant Treatment of Residual Breast Cancer With Adjuvant Bevacizumab Alone, With Metronomic or Standard-Dose Chemotherapy: A Combined Analysis of DFCI 05-055 and DFCI 09-134/TBCRC 012/ABCDE Clinical Trials. Clin Breast Cancer. 2025 Jun;25(4):e419-e430.e5. doi: 10.1016/j.clbc.2024.12.018. Epub 2024 Dec 31.

    PubMed 39890560

Questions about this trial

What is this clinical trial studying?

A Phase 2 study testing Bevacizumab, Cyclophosphamide and Methotrexate in people with Breast Cancer, run by Dana-Farber Cancer Institute 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?

The sponsor lists 14 inclusion and 25 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 19 Jan 2022. 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 19 Jan 2022). 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?

Median 3-year Recurrence-free Survival (RFS) (time frame: Disease assessments occurred every 12 weeks on treatment and every 6 months in long-term follow-up up to 7.5 years.). 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 NCT00925652, 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 19 Jan 2022.

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