Breast CancerPhase 2NCT00428922
Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients
A Phase 2 study testing Trastuzumab, Bevacizumab and Docetaxel in people with Breast Cancer, run by Bhuvaneswari Ramaswamy at 3 sites in United States.
Trial summary
The primary objectives are to determine the progression-free survival (PFS) and to evaluate safety of the trastuzumab, bevacizumab and docetaxel regimen. 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?
- Trastuzumab, Bevacizumab and Docetaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 26 participants
- Where
- 3 sitesUnited States
- Study dates
- 14 Jun 2007to 7 Feb 2017
- 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 confirmed breast cancer with evidence of metastatic disease
- HER2 3+ or FISH (fluorescent in situ hybridization)+
- Age ≥ 18 years
- No prior trastuzumab, except as given in the adjuvant or neoadjuvant setting.
- No prior chemotherapy in the metastatic setting.
Who cannot join
- CNS (central nervous system) metastases
- Prior radiation therapy within the last 4 weeks
- Pregnant (positive pregnancy test) or lactating women
- Major surgical procedure, open biopsy, non-healing wounds, or significant traumatic injury within 28 days prior to starting study or anticipation of need for major surgical procedure during the study
- Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to start of study.
Trial locations and contacts
3 sites in 1 country.
United States3 sites
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
Ohio State University
Columbus, Ohio, 43210
University of Pittsburgh
Pittsburgh, Pennsylvania, 15213
About this study
Official title: Phase II Trial of Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients
The primary objectives are to determine the progression-free survival (PFS) and to evaluate safety of the trastuzumab, bevacizumab and docetaxel regimen.
Read the detailed description
Rationale: Antibodies are proteins that are normally part of the immune system that bind to foreign agents in the body. Researchers manufacture antibodies outside of the human body that bind to specific targets such as proteins in cancer cells. Herceptin is a monoclonal antibody that binds to the human epidermal growth factor receptor (HER-2), and can kill HER2-positive cancer cells. Herceptin is used to treat breast cancer that is HER2-positive, and has spread after treatment with other drugs. Bevacizumab is a signal transduction inhibitor that works by preventing the growth of new blood vessels from surrounding tissue into tumors. Bevacizumab specifically inhibits the vascular endothelial growth factor (VEGF), a substance made by cells that stimulates new blood vessel formation. Research indicates that HER-2 signaling helps to induce VEGF expression. Therefore, cancer treatments targeting both HER-2 and VEGF may improve anti-cancer efficacy in patients. Docetaxel is a chemotherapy agent used against breast and other types of cancer. The current study builds on previous research suggesting the safety and potential for efficacy with combination trastuzumab, bevacizumab, and docetaxel.
Purpose: The primary objectives are to determine the progression free survival and evaluate the safety of trastuzumab, bevacizumab, and docetaxel. Secondary objectives are to assess early changes in circulating tumor cells and circulating endothelial cells as predictors of progression free survival and clinical benefit, as well as to determine the overall clinical benefit rate.
Treatment: Study participants will be given trastuzumab, bevacizumab, and docetaxel. All study drugs will be given through intravenous infusions once every 21 days. A cycle is considered 3 weeks. A minimum of 6 study treatment cycles is required unless study participants experience disease growth or intolerable toxicity. The decision to stop docetaxel after 6 cycles is up to the discretion of the treating physician and the patient. Study participants who are deriving a benefit from the study drugs may continue on trastuzumab and bevacizumab alone. Several tests and exams will be given throughout the study to closely monitor study participants.
- Conditions
- Breast Cancer
- Being tested
- Trastuzumab, Bevacizumab, Docetaxel
- Keywords
- Metastatic, Breast Cancer, MBC
- Medical subject headings
- Breast Neoplasms, Neoplasm Metastasis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TrastuzumabDrug
Also called Herceptin
administered every three weeks on day 1, every 21 days. The dose given will be 6 mg/kg. The initial loading dose is 8mg/kg and is administered as a 90-minute infusion. Thereafter, the maintenance dose is 6mg/kg every three weeks administered as a 30 minute infusion (unless the treating physician indicates a longer infusion duration is warranted). Trastuzumab is given prior to bevacizumab. Trastuzumab is to be continued until disease progression or unacceptable toxicity.
BevacizumabDrug
Also called Avastin
administered every three weeks on day 1, every 21 days. The dose given will be 15 mg/kg. The initial dose is administered over 90 minutes. If the first infusion is well tolerated, the second dose is given over 60 minutes, and if that is well tolerated, then subsequent doses may be given over 30 minutes. Avastin is given after trastuzumab and prior to docetaxel.
DocetaxelDrug
Also called Taxotere
administered every three weeks on day 1, every 21 days. The dose given will be 75 mg/M². All doses of docetaxel are administered over 60 minutes. Docetaxel is given after trastuzumab and bevacizumab.
| Study group | Role | What they receive |
|---|---|---|
| Trastuzumab, Bevacizumab, and Docetaxel | Experimental | Trastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M²] Receives: Drug: Trastuzumab; Drug: Bevacizumab; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen.
The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months.
Measured: up to 3 years
Secondary outcomes (3)
Changes in CTCs as Predictors of PFS and Clinical Benefit
Circulating tumor cells (CTCs) evaluated at baseline (day 1 of treatment) and after 1 treatment cycle (day 22 prior to cycle 2 treatment).
Measured: Day 1 and Day 22
Overall Clinical Benefit Rate (CR+PR+SD)
Defined as best response of CR or PR or stable disease for at least 24 weeks. Per Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0) for target lesions and assessed by MRI and/or CT: Partial Response (PR), >=30% decrease in the sum of the longest diameter of target lesions; Stable Disease (SD), neither sufficient shrinkage to qualify for a Partial Response nor sufficient increase to qualify for Progression of Disease (POD); POD, 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions; Complete Response (CR), Disappearance of all target lesions
Measured: at least 24 weeks
Changes in CECs as Predictors of PFS and Clinical Benefit
Circulating endothelial cells (CECs) are to be collected day 1 prior to treatment and day 22 prior to treatment. These samples are to be collected at the PI's discretion based upon the availability of the cell processing laboratory, the patients will be informed when consented if the samples will collected or not.
Measured: Day 1 and Day 22
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted30 Jan 2007 (estimated)
- Study start14 Jun 2007
- Primary completion1 Nov 2012
- Study completion7 Feb 2017
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.
- 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
- 26 participants (actual)
Sponsor and investigators
- Lead sponsor
- Bhuvaneswari Ramaswamy
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Bhuvaneswari Ramaswamy, Ohio State University Comprehensive Cancer Center
- Investigators
- Bhuvaneswari Ramaswamy, MD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00428922
- Sponsor's protocol ID
- OSU-06027
- Other IDs
- NCI-2011-03219
- Status last verified
- Jul 2018
- First submitted
- 29 Jan 2007
- Last updated
- 9 Aug 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Puhalla S, Mrozek E, Young D, Ottman S, McVey A, Kendra K, Merriman NJ, Knapp M, Patel T, Thompson ME, Maher JF, Moore TD, Shapiro CL. Randomized phase II adjuvant trial of dose-dense docetaxel before or after doxorubicin plus cyclophosphamide in axillary node-positive breast cancer. J Clin Oncol. 2008 Apr 1;26(10):1691-7. doi: 10.1200/JCO.2007.14.3941. Epub 2008 Mar 3.
PubMed 18316792
Study at a glance
From the registry record, last updated by the sponsor on 9 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Trastuzumab (Herceptin), Bevacizumab, and Docetaxel (Taxotere) Trial in Stage IV Metastatic Breast Cancer (MBC) Patients
- ClinicalTrials.gov ID
- NCT00428922
- Acronym / sponsor ID
- OSU-06027
- Conditions
- Breast Cancer
- Keywords
- Metastatic, Breast Cancer, MBC
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 26 participants (actual)
- Lead sponsor
- Bhuvaneswari RamaswamyUniversity, hospital or other
- Collaborators
- Genentech, Inc., Case Comprehensive Cancer Center, University of Pittsburgh
- Study start
- 14 Jun 2007 (actual)
- Primary completion
- 1 Nov 2012 (actual)
- Study completion
- 7 Feb 2017 (actual)
- First posted
- 30 Jan 2007 (estimated)
- Results
- Posted 12 Feb 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The primary objectives are to determine the progression-free survival (PFS) and to evaluate safety of the trastuzumab, bevacizumab and docetaxel regimen.
Detailed description
Rationale: Antibodies are proteins that are normally part of the immune system that bind to foreign agents in the body. Researchers manufacture antibodies outside of the human body that bind to specific targets such as proteins in cancer cells. Herceptin is a monoclonal antibody that binds to the human epidermal growth factor receptor (HER-2), and can kill HER2-positive cancer cells. Herceptin is used to treat breast cancer that is HER2-positive, and has spread after treatment with other drugs. Bevacizumab is a signal transduction inhibitor that works by preventing the growth of new blood vessels from surrounding tissue into tumors. Bevacizumab specifically inhibits the vascular endothelial growth factor (VEGF), a substance made by cells that stimulates new blood vessel formation. Research indicates that HER-2 signaling helps to induce VEGF expression. Therefore, cancer treatments targeting both HER-2 and VEGF may improve anti-cancer efficacy in patients. Docetaxel is a chemotherapy agent used against breast and other types of cancer. The current study builds on previous research suggesting the safety and potential for efficacy with combination trastuzumab, bevacizumab, and docetaxel.
Purpose: The primary objectives are to determine the progression free survival and evaluate the safety of trastuzumab, bevacizumab, and docetaxel. Secondary objectives are to assess early changes in circulating tumor cells and circulating endothelial cells as predictors of progression free survival and clinical benefit, as well as to determine the overall clinical benefit rate.
Treatment: Study participants will be given trastuzumab, bevacizumab, and docetaxel. All study drugs will be given through intravenous infusions once every 21 days. A cycle is considered 3 weeks. A minimum of 6 study treatment cycles is required unless study participants experience disease growth or intolerable toxicity. The decision to stop docetaxel after 6 cycles is up to the discretion of the treating physician and the patient. Study participants who are deriving a benefit from the study drugs may continue on trastuzumab and bevacizumab alone. Several tests and exams will be given throughout the study to closely monitor study participants.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Trastuzumab, Bevacizumab, and Docetaxel | Experimental | Drug: Trastuzumab, Drug: Bevacizumab, Drug: DocetaxelTrastuzumab [6mg/kg], Bevacizumab [15mg/kg], and Docetaxel [75 mg/M²] |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Histologically confirmed breast cancer with evidence of metastatic disease
- HER2 3+ or FISH (fluorescent in situ hybridization)+
- Age ≥ 18 years
- No prior trastuzumab, except as given in the adjuvant or neoadjuvant setting.
- No prior chemotherapy in the metastatic setting.
Key exclusion criteria (5 listed)
- CNS (central nervous system) metastases
- Prior radiation therapy within the last 4 weeks
- Pregnant (positive pregnancy test) or lactating women
- Major surgical procedure, open biopsy, non-healing wounds, or significant traumatic injury within 28 days prior to starting study or anticipation of need for major surgical procedure during the study
- Minor surgical procedures such as fine needle aspirations or core biopsies within 7 days prior to start of study.
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 |
|---|---|---|
| TrastuzumabAlso: Herceptinadministered every three weeks on day 1, every 21 days. The dose given will be 6 mg/kg. The initial loading dose is 8mg/kg and is administered as a 90-minute infusion. Thereafter, the maintenance dose is 6mg/kg every three weeks administered as a 30 minute infusion (unless the treating physician indicates a longer infusion duration is warranted). Trastuzumab is given prior to bevacizumab. Trastuzumab is to be continued until disease progression or unacceptable toxicity. | Drug | Trastuzumab, Bevacizumab, and Docetaxel |
| BevacizumabAlso: Avastinadministered every three weeks on day 1, every 21 days. The dose given will be 15 mg/kg. The initial dose is administered over 90 minutes. If the first infusion is well tolerated, the second dose is given over 60 minutes, and if that is well tolerated, then subsequent doses may be given over 30 minutes. Avastin is given after trastuzumab and prior to docetaxel. | Drug | Trastuzumab, Bevacizumab, and Docetaxel |
| DocetaxelAlso: Taxotereadministered every three weeks on day 1, every 21 days. The dose given will be 75 mg/M². All doses of docetaxel are administered over 60 minutes. Docetaxel is given after trastuzumab and bevacizumab. | Drug | Trastuzumab, Bevacizumab, and Docetaxel |
Primary outcome
Progression-free Survival (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen.
Time frame: up to 3 years
The trial was designed as a single-stage phase II rather then usual two-stage design because of the progression free survival (PFS) primary endpoint, as it is impractical to wait to assess PFS for patients in the first stage. We will consider a PFS of 50% at twelve months (median PFS of 12 months) or less uninteresting and a PFS of 70% at twelve months (median PFS of twenty months) worthy of pursuing the regimen in a future trials. The single-stage design is as follows: p0=0.50, p1=0.70, α=0.10, β= 0.10. This leads to a total sample size of 39 patients, 24 or higher of who are progression-free at 12 months.
3 secondary outcomes
Changes in CTCs as Predictors of PFS and Clinical Benefit
Time frame: Day 1 and Day 22
Overall Clinical Benefit Rate (CR+PR+SD)
Time frame: at least 24 weeks
Changes in CECs as Predictors of PFS and Clinical Benefit
Time frame: Day 1 and Day 22
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 9 Aug 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 18316792Puhalla S, Mrozek E, Young D, Ottman S, McVey A, Kendra K, Merriman NJ, Knapp M, Patel T, Thompson ME, Maher JF, Moore TD, Shapiro CL. Randomized phase II adjuvant trial of dose-dense docetaxel before or after doxorubicin plus cyclophosphamide in axillary node-positive breast cancer. J Clin Oncol. 2008 Apr 1;26(10):1691-7. doi: 10.1200/JCO.2007.14.3941. Epub 2008 Mar 3.
- JameslineLink provided by the sponsor.
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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.
Bhuvaneswari Ramaswamy, MD principal investigator
Ohio State University
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 Trastuzumab, Bevacizumab and Docetaxel in people with Breast Cancer, run by Bhuvaneswari Ramaswamy 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 5 inclusion and 5 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: finished, as of the sponsor's last update on 9 Aug 2018. 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 12 Feb 2016). 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 (PFS) and to Evaluate Safety of the Trastuzumab, Bevacizumab and Docetaxel Regimen. (time frame: up to 3 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 NCT00428922, 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 Aug 2018.