Invasive Breast CancerPhase 2NCT00635050
Therapy for Locally Advanced Breast Cancer Using Doxil, Paclitaxel, and Cyclophosphamide With Avastin
A Phase 2 study testing Doxil, Paclitaxel, Cyclophosphamide, Avastin in people with Invasive Breast Cancer, run by University of Alabama at Birmingham at 1 site in United States.
Trial summary
This study will evaluate the rate of pathological complete response (pCR) to the sequential therapy of Doxil, paclitaxel, and cyclophosphamide with concurrent Avastin for patients with locally advanced invasive (T2,T3, Nany, M0) breast carcinoma. Read more about this study
- Who is it for?
- Ages 19 years and older, women only
- Conditions the study is for
- Invasive Breast Cancer
- What is being tested?
- Doxil, Paclitaxel, Cyclophosphamide, Avastin
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 32 participants
- Where
- 1 siteUnited States
- Study dates
- Mar 2008to Jun 2015
- 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 19 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Histologically confirmed, measurable, invasive breast carcinoma T >2cm, Nany, M0.
- Patients with node-negative, ER or PR-positive tumors ≤4 cm in size whose tumors are low risk (defined as a score of 0-17) on an Oncotype DX profile are not eligible.
- 19 years of age or greater
- Known ER, PR and HER-2 status (FISH assay to be done on specimens with 2+ or 3+ immunohistochemical staining for HER-2): patients with gene amplification on FISH study will be considered to be HER-2 positive. Patients for this study must be FISH negative if immunohistochemical stain is 2+ or 3+ positive; patients with negative, 0 or 1+ immunohistochemical stain for HER-2 are eligible.
- Known axillary nodal status: aspiration cytology or biopsy
- Documented menopausal status premenopausal (having menstrual periods or FSH <35) or postmenopausal (≥12 months since last menstrual period with intact uterus and at least one ovary or FSH ≥35 or previous bilateral oophorectomy
Show all 31Show fewer
- Non-pregnant if premenopausal (negative serum or urine pregnancy test within 7 days of starting chemotherapy) and not breast feeding
- Patients with reproductive potential must use an adequate contraceptive method (e.g., abstinence, intrauterine device, barrier device with spermicide or surgical sterilization) during treatment and for three months after completing treatment.
- Life expectancy of less than 12 weeks
- Current, recent (within 4 weeks of the first infusion of this study), or planned participation in an experimental drug study other than a Genentech-sponsored Avastin cancer study
- Pregnant or lactating women.
- History of cardiac disease, with New York Heart Association Grade II or greater or clinical evidence of congestive heart failure.
- Serious comorbid medical conditions which would impair the ability to receive chemotherapy on time
- Previous invasive cancer within the last 5 years
- Altered mental status or dementia which would interfere with understanding of informed consent and ability to comply with study and follow-up procedures.
- Hypersensitivity to Doxil, doxorubicin, cyclophosphamide, cremophore (contained in teniposide, cyclosporine, and vitamin K), or to any component of Avastin
- Inadequately controlled hypertension (defined as blood pressure of >150/100 mmHg on antihypertensive medication)
- Unstable angina pectoris
- History of myocardial infarction or unstable angina within 12 months prior to beginning therapy
- History of stroke or TIA at any time
- Clinically significant vascular (e.g., aortic aneurysm requiring surgical repair or recent peripheral arterial thrombosis, aortic dissection) or peripheral vascular disease with 6 months prior to beginning therapy
- History of hemoptysis (greater than or equal to 1/2 teaspoon of bright red blood per episode) within 1 month prior to beginning therapy
- Evidence of bleeding diathesis or significant coagulopathy (in the absence of therapeutic anticoagulation)
- Major surgical procedure, open biopsy, or significant traumatic injury within 28 days prior to beginning therapy or anticipation of need for major surgical procedure during the course of the study
- Patients must have a 2-d echocardiogram indicating an ejection fraction of > 50% within 42 days prior to first dose of study drug. The method used at baseline must be used for later monitoring.
- No distant metastases on bone scan and on CT scans of chest and abdomen (no metastasis on optional PET scan is an acceptable alternative; if PET scan is done for any reason it must show no evidence of distant metastasis). Baseline PET scan is recommended but not required for all patients.
- No CNS metastasis
- Hbg ≥9 gm, platelets ≥100,000, granulocytes ≥1000, total or direct bilirubin ≤1.2, creatinine ≤2.0 and urine protein:creatinine ratio <1.0
- No prior chemotherapy or radiotherapy and ≤4 weeks of prior antiestrogen or aromatase inhibitor therapy
- No concomitant hormone replacement (i.e. estrogen or progestin) therapy
- PS less than or equal to one
Who cannot join
- Minor surgical procedure (excluding placement of a vascular access device) such as fine needle aspiration or core needle biopsy within 7 days of beginning therapy
- Urine protein:creatinine ratio ≥1.0 at initial screening
- Known hypersensitivity to any component of Avastin
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of beginning therapy
- Serious, non-healing wound, active ulcer, or untreated bone fracture
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- Known CNS metastasis, except for treated brain metastasis. Treated brain metastases are defined as having no evidence of progression or hemorrhage after treatment and no ongoing requirement for dexamethasone, as ascertained by clinical examination and brain imaging (MRI or CT) during the screening period. Anticonvulsants (stable dose) are allowed. Treatment for brain metastases may include whole brain radiotherapy (WBRT), radiosurgery (RS; Gamma Knife, LINAC, or equivalent) or a combination as deemed appropriate by the treating physician. Patients with CNS metastases treated by neurosurgical resection or brain biopsy performed within 3 months prior to Day 1 will be excluded.
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Alabama at Birmingham
Birmingham, Alabama, 35294 - 0104
About this study
Official title: Phase II Trial of Primary Systemic Therapy for Locally Advanced Breast Cancer Using Sequential Doxil, Paclitaxel, and Cyclophosphamide With Concurrent Avastin
This study will evaluate the rate of pathological complete response (pCR) to the sequential therapy of Doxil, paclitaxel, and cyclophosphamide with concurrent Avastin for patients with locally advanced invasive (T2,T3, Nany, M0) breast carcinoma. Also, the study will evaluate the clinical and subclinical cardiotoxic effect(s) of this regimen, assess how feasible and safe the study is. Survival without any progression of disease will also be calculated.
A regimen of chemotherapy will be given to replicate the high rate of pCR seen with conventional chemotherapy in patients with locally advanced breast cancer. Doxil will substitute the normally given doxorubicin. It is expected that the low effect or minimal effect of Doxil on cardiac function will minimize any additional risk of cardiotoxicity from Avastin. It is expected that clinical and subclinical rates of cardiotoxicity will be very low at the total doses to be given in this clinical trial.
Read the detailed description
In this trial, an attempt will be made to replicate the high rate of pathological complete response seen after conventional chemotherapy in patients with locally advanced breast cancer, using a regimen in which Doxil is substituted for conventional doxorubicin. We expect that the low or minimal effect on cardiac function produced by Doxil will minimize any additional risk of cardiotoxicity from Avastin. We will also measure left ventricular ejection fractions before and after treatment to see if the substantial rate of subclinical cardiotoxicity reported by Swain et al 5 and Perez et al 7 can be avoided. The reported rates of cardiotoxicity after treatment with relatively high doses of Doxil are substantially lower than those of doxorubicin; few data are available to estimate the rate of cardiotoxicity of Doxil in patients treated with only about 100 mg/m2 total accumulated dose, the dose to be utilized here. The drug has been used in a few patients in the primary systemic therapy setting, with no reported clinical cardiotoxicity.
The expectation is that clinical and subclinical rates of cardiotoxicity will be very low or negligible at the total doses to be used here.
- Conditions
- Invasive Breast Cancer
- Being tested
- Doxil, Paclitaxel, Cyclophosphamide, Avastin
- Keywords
- 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.
Doxil, Paclitaxel, Cyclophosphamide, AvastinDrug
Also called Bevacizumab (Avastin)
Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation.
Regimen B: Doxil 30 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3. Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation.
| Study group | Role | What they receive |
|---|---|---|
| Doxil, Paclitaxel, Cyclophosphamide + Avastin | Experimental | Two stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, in patients with locally advanced invasive breast cancer. Receives: Drug: Doxil, Paclitaxel, Cyclophosphamide, Avastin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Rate of Achievement of Pathological Complete Response (pCR)
Results of the pathologic evaluation of the surgical specimen(s) from operation (segmental or total mastectomy) will be used to report the overall complete pathological response rate. Criteria used were those described by Kaufmann et al, Journal of Clinical Oncology 2003; 21(13):2600-2608. The definition of pCR used from this source was absence of invasive cancer in both resected breast tissue and in resected axillary nodes.
Measured: After completion of at least 8 of the 9 chemotherapy doses and operation.
Secondary outcomes (3)
Number of Participant With Clinical or Subclinical Cardiotoxicity
Left ventricular ejection fraction (LVEF) measurements and clinical examination at baseline and at end of therapy will be used.
Measured: Prior to treatment and at completion of chemotherapy
Calculate Progression Free Survival
Progression free survival (PFS) will be defined as survival without local recurrence of breast cancer and without the development of distant metastasis. Death from any cause will be included as an event. The Kaplan-Meier nonparametric method will be used to estimate progression free survival.
Measured: 5 years
Assess Toxicities of Regimen Including Hand Foot Syndrome
patients who receive any treatment drugs will be included for toxicity evaluation. Adverse events will be summarized with frequencies and proportions of study participants exhibiting adverse events. The severity of adverse events (none, mild, moderate, severe) and their relationship to the product will be presented.
Measured: Baseline, every 2 weeks during treatment, and at completion of therapy. Every 3 weeks during postoperative Avastin
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Mar 2008 (estimated)
- Study startMar 2008
- Primary completionDec 2014
- Study completionJun 2015
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 Invasive Breast CancerStudies of the same condition, open and under way.
- More trials run by University of Alabama at BirminghamThe 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
- 32 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Alabama at Birmingham
- Sponsor type
- University, hospital or other
- Collaborators
- Ortho Biotech, Inc., Genentech, Inc.
- Responsible party
- Principal investigator, John Carpenter, MD, University of Alabama at Birmingham
- Investigators
- John Carpenter, M.D., Principal investigator, University of Alabama at Birmingham
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00635050
- Sponsor's protocol ID
- F070824009
- Other IDs
- UAB 0493
- Status last verified
- Jun 2016
- First submitted
- 6 Mar 2008
- Last updated
- 14 Jul 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jul 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Trial of Primary Systemic Therapy for Locally Advanced Breast Cancer Using Sequential Doxil, Paclitaxel, and Cyclophosphamide With Concurrent Avastin
- ClinicalTrials.gov ID
- NCT00635050
- Acronym / sponsor ID
- F070824009
- Conditions
- Invasive Breast Cancer
- Keywords
- Breast cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 32 participants (actual)
- Lead sponsor
- University of Alabama at BirminghamUniversity, hospital or other
- Collaborators
- Ortho Biotech, Inc., Genentech, Inc.
- Study start
- Mar 2008
- Primary completion
- Dec 2014 (actual)
- Study completion
- Jun 2015 (actual)
- First posted
- 13 Mar 2008 (estimated)
- Results
- Posted 15 Jun 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will evaluate the rate of pathological complete response (pCR) to the sequential therapy of Doxil, paclitaxel, and cyclophosphamide with concurrent Avastin for patients with locally advanced invasive (T2,T3, Nany, M0) breast carcinoma. Also, the study will evaluate the clinical and subclinical cardiotoxic effect(s) of this regimen, assess how feasible and safe the study is. Survival without any progression of disease will also be calculated.
A regimen of chemotherapy will be given to replicate the high rate of pCR seen with conventional chemotherapy in patients with locally advanced breast cancer. Doxil will substitute the normally given doxorubicin. It is expected that the low effect or minimal effect of Doxil on cardiac function will minimize any additional risk of cardiotoxicity from Avastin. It is expected that clinical and subclinical rates of cardiotoxicity will be very low at the total doses to be given in this clinical trial.
Detailed description
In this trial, an attempt will be made to replicate the high rate of pathological complete response seen after conventional chemotherapy in patients with locally advanced breast cancer, using a regimen in which Doxil is substituted for conventional doxorubicin. We expect that the low or minimal effect on cardiac function produced by Doxil will minimize any additional risk of cardiotoxicity from Avastin. We will also measure left ventricular ejection fractions before and after treatment to see if the substantial rate of subclinical cardiotoxicity reported by Swain et al 5 and Perez et al 7 can be avoided. The reported rates of cardiotoxicity after treatment with relatively high doses of Doxil are substantially lower than those of doxorubicin; few data are available to estimate the rate of cardiotoxicity of Doxil in patients treated with only about 100 mg/m2 total accumulated dose, the dose to be utilized here. The drug has been used in a few patients in the primary systemic therapy setting, with no reported clinical cardiotoxicity.
The expectation is that clinical and subclinical rates of cardiotoxicity will be very low or negligible at the total doses to be used here.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Doxil, Paclitaxel, Cyclophosphamide + Avastin | Experimental | Drug: Doxil, Paclitaxel, Cyclophosphamide, AvastinTwo stage phase II single arm trial to evaluate the pathologic complete response rate to sequential dose dense chemotherapy using Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, in patients with locally advanced invasive breast cancer. |
Who may qualify
- Ages
- 19 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (31 listed)
- Histologically confirmed, measurable, invasive breast carcinoma T >2cm, Nany, M0.
- Patients with node-negative, ER or PR-positive tumors ≤4 cm in size whose tumors are low risk (defined as a score of 0-17) on an Oncotype DX profile are not eligible.
- 19 years of age or greater
- Known ER, PR and HER-2 status (FISH assay to be done on specimens with 2+ or 3+ immunohistochemical staining for HER-2): patients with gene amplification on FISH study will be considered to be HER-2 positive. Patients for this study must be FISH negative if immunohistochemical stain is 2+ or 3+ positive; patients with negative, 0 or 1+ immunohistochemical stain for HER-2 are eligible.
- Known axillary nodal status: aspiration cytology or biopsy
Key exclusion criteria (7 listed)
- Minor surgical procedure (excluding placement of a vascular access device) such as fine needle aspiration or core needle biopsy within 7 days of beginning therapy
- Urine protein:creatinine ratio ≥1.0 at initial screening
- Known hypersensitivity to any component of Avastin
- History of abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within 6 months of beginning therapy
- Serious, non-healing wound, active ulcer, or untreated bone fracture
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 |
|---|---|---|
| Doxil, Paclitaxel, Cyclophosphamide, AvastinAlso: Bevacizumab (Avastin)Regimen A: Doxil 25 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3 . Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin 15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. Regimen B: Doxil 30 mg/M2 iv and Avastin 10 mg/kg iv every 2 weeks x 3, then paclitaxel 175 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3, then cyclophosphamide 600 mg/M2 i.v. and Avastin 10 mg/kg iv every 2 weeks x 3. Patients who experience <pCR to primary chemotherapy will receive an additional year of Avastin15 mg/kg iv every 3 weeks, beginning 6-8 weeks after operation. | Drug | Doxil, Paclitaxel, Cyclophosphamide + Avastin |
Primary outcome
Rate of Achievement of Pathological Complete Response (pCR)
Time frame: After completion of at least 8 of the 9 chemotherapy doses and operation.
Results of the pathologic evaluation of the surgical specimen(s) from operation (segmental or total mastectomy) will be used to report the overall complete pathological response rate. Criteria used were those described by Kaufmann et al, Journal of Clinical Oncology 2003; 21(13):2600-2608. The definition of pCR used from this source was absence of invasive cancer in both resected breast tissue and in resected axillary nodes.
3 secondary outcomes
Number of Participant With Clinical or Subclinical Cardiotoxicity
Time frame: Prior to treatment and at completion of chemotherapy
Calculate Progression Free Survival
Time frame: 5 years
Assess Toxicities of Regimen Including Hand Foot Syndrome
Time frame: Baseline, every 2 weeks during treatment, and at completion of therapy. Every 3 weeks during postoperative Avastin
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jul 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
John Carpenter, M.D. principal investigator
University of Alabama at Birmingham
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 Doxil, Paclitaxel, Cyclophosphamide, Avastin in people with Invasive Breast Cancer, run by University of Alabama at Birmingham 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 31 inclusion and 7 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 14 Jul 2016. 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 15 Jun 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?
Rate of Achievement of Pathological Complete Response (pCR) (time frame: After completion of at least 8 of the 9 chemotherapy doses and operation.). 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 14 Jul 2016.