Breast CancerPhase 1/2NCT00468585
Study of Biweekly Capecitabine Dosing With Bevacizumab for the Treatment of Metastatic Breast Cancer Based Upon the Norton-Simon Mathematical Model
A Phase 1/2 study testing Capecitabine and Bevacizumab in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 5 sites in United States.
Trial summary
The purpose of this study is to find out what effects (both good and bad) that capecitabine has on you and your breast cancer when given in a novel schedule in combination with the antibody therapy, bevacizumab. 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?
- Capecitabine and Bevacizumab
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 62 participants
- Where
- 5 sitesUnited States
- Study dates
- Jun 2005to Apr 2011
- Phase
- Phase 1/2
- 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
- Patient (male or female) with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC either by histology or cytology.
- Clinical evidence of metastatic breast cancer, non-amenable to surgery or radiation therapy with curative intent.
- Presence of at least one measurable metastatic lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: greater than or equal to 10 mm measured by spiral CT or greater than or equal to 20 mm measured by conventional techniques.
- Any number of prior endocrine or biologic therapies is permitted on this trial. In addition, patients may be untreated in the metastatic setting or have received any number of prior cytotoxic regimens. All previous chemotherapy must have been discontinued at least 3 weeks prior to study entry. All acute toxic effects (excluding alopecia or neurotoxicity) of any prior therapy must have resolved to NCI CTC (Version 3) Grade less than or equal to 1.
- Endocrine therapy with an aromatase inhibitor, SERM (ie, tamoxifen) or fulvestrant is permitted within 4 weeks of study entry, however concurrent therapy with these drugs is not acceptable.
- ECOG performance status of 0, 1 or 2.
Show all 16Show fewer
- Patients must be either HER2-negative or HER2-positive and no longer a candidate for trastuzumab therapy. HER2-negative is defined as 0 or 1+ staining on immunohistochemistry or FISH negative for gene amplification. HER2-positive is defined as 3+ staining on immunohistochemistry or FISH positive for gene amplification.
- Age greater than or equal to 18 years old.
- Baseline laboratory data within the following limits:
- Absolute neutrophil count (ANC) >1.5 x 10^9/L
- Platelets > 100 x 10^9/L
- Estimated creatinine clearance greater than or equal to 50 ml/min by - Cockcroft-Gault equation
- Total serum bilirubin <1.5 x upper normal limit
- ALT, AST < 2.5x upper normal limit (or <5x upper normal limit in the case of liver metastases)
- Alkaline phosphatase < 2.5x upper normal limit (or >5x upper normal limit in the case of liver metastases or >10x upper normal limit in the case of bone disease)
- Serum or urine pregnancy test for females of childbearing potential Negative within 14 days of starting treatment
Who cannot join
- Pregnant or nursing women may not participate. Patients of reproductive potential may not participate unless they have agreed to use an effective method of contraception and to continue contraception for 30 days from the date of the last study drug administration. Postmenopausal woman must be amenorrheic for at least 12 months to be considered of nonchildbearing potential.
- Life expectancy < 3 months.
- Serious, uncontrolled, concurrent infection.
- Any prior fluoropyrimidine therapy with the exception of adjuvant administration. Adjuvant fluoropyrimidine containing therapy must be completed at least 6 months prior to enrollment.
- Prior severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil. A history of DPD deficiency will exclude patients from the trial.
- Completion of previous chemotherapy regimen <3 weeks prior to the start of study treatment.
Show all 25Show fewer
- Prior adjuvant hormonal therapy is permitted. Use of an aromatase inhibitor, anti-estrogen or fulvestrant must be discontinued prior to treatment start.
- Biologic therapy (eg, bevacizumab,trastuzumab) for the treatment of metastatic disease must be discontinued >3 weeks from the start of protocol treatment.
- HER2-positive patients who are candidates for treatment with trastuzumab are excluded from this trial as the concurrent use of trastuzumab may confound study results.
- History of prior malignancy with the following exceptions: adequately treated basal cell or squamous cell carcinoma, in situ cervical cancer, adequately treated Stage I or II cancer from which the patient is currently in complete remission (with no evidence of disease) for more than five years.
- Non-malignant systemic disease (cardiovascular, renal, hepatic etc) that would preclude any of the study therapy drugs. Specifically excluded are the following cardiac conditions:
- Inadequately controlled hypertension (defined as blood pressure of >150/100 mmHg on antihypertensive medications)
- Any prior history of hypertensive crisis or hypertensive encephalopathy
- New York Heart Association (NYHA) Class II or greater congestive heart failure
- History of myocardial infarction or unstable angina within 6 months
- History of stroke or transient ischemic attack within 6 months
- Significant vascular disease or symptomatic peripheral vascular disease
- Capecitabine is contraindicated in patients with a creatinine clearance of <30 ml/min.Patients with a creatinine clearance less than 50 ml/minute by Cockroft and Gault Equation will be excluded from the trial.
- Patients with symptomatic CNS metastases that remain untreated by radiation therapy are excluded from this trial. The presence of asymptomatic brain metastases or brain metastases that have been previously irradiated are not grounds for trial exclusion for the phase I study however, these patients are excluded from the phase II portion of the trial.
- History of uncontrolled seizures, central nervous system disorders or psychiatric disability judged by the investigator to be clinically significant, precluding informed consent, or interfering with compliance of oral drug intake.
- Other severe, acute or chronic, medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or study drug administration or may interfere with the interpretation of study results. Any of the above criteria that in the judgment of the investigator would make the subject inappropriate for entry into this study.
- Presence of uncontrolled gastrointestinal malabsorption syndrome.
- Concurrent use of oral warfarin anticoagulant therapy is not permitted due to serious drug interactions with capecitabine. Full dose anticoagulation with low molecular weight heparin or other (non-warfarin) anticoagulant is permitted.
- Unwillingness to give written informed consent or unwillingness to participate or inability to comply with the protocol for the duration of the study. Willingness and ability to comply with scheduled visits, treatment plan, laboratory tests and other study procedures are necessary for participation in this clinical trial.
- Concurrent radiation therapy is not permitted during treatment on protocol.
Trial locations and contacts
5 sites in 1 country.
5 sites in 1 country
United States5 sites
Memorial Sloan-Kettering at Basking Ridge
Basking Ridge, New Jersey, 07920
Memorial Sloan-Kettering Cancer Center at Commack
Commack, New York, 11725
Memorial Sloan-Kettering Cancer Center 1275 York Avenue
New York, New York, 10021
Memorial Sloan-Kettering Cancer Center at Mercy Medical Center
Rockville Centre, New York, 11570
Memorial Sloan-Kettering Cancer Center at Phelps Memorial Hospital Center
Sleepy Hollow, New York, 10591
About this study
Official title: A Multicenter, Phase I/II Study of Every Other Week Capecitabine Dosing With Bevacizumab for the Treatment of Metastatic Breast Cancer Based Upon the Norton-Simon Mathematical Model
The purpose of this study is to find out what effects (both good and bad) that capecitabine has on you and your breast cancer when given in a novel schedule in combination with the antibody therapy, bevacizumab. Capecitabine (Xeloda®) is an anticancer drug that was approved by FDA in 1998 for treating metastatic breast cancer. Capecitabine is a pill that blocks the way cancer cells multiply and grow. Usually, this medicine is taken twice a day for fourteen days in a row.
Patients then get a break from the drug for seven days. With this schedule and usual dose, some patients on capecitabine have experienced side effects that interfered with their daily comfort.Different doses and schedules of capecitabine have been studied in animal studies and in people with colon cancer. Mathematic modeling has been used to better understand these results.Information from these experiments leads us to ask if 7 days of treatment with capecitabine followed by a 7-day break is both safer and more active against breast cancer. The study you are considering is a first step in this direction and is designed to demonstrate both safety and activity.
Read more
Bevacizumab is a biologic therapy that targets the growth of blood vessels which tumors need to grow. Women whose breast cancer spread to other parts of their bodies lived longer without their cancers growing when they were treated with bevacizumab and chemotherapy. Bevacizumab was tested with the 14-day/7-day schedule of capecitabine. These two medicines are safe when given together and seem to work better against breast cancer than capecitabine alone.
This study is designed to answer the questions:
- What are the side effects of bevacizumab and capecitabine when given in this different schedule and how often do they occur?
- When given in this schedule, does capecitabine with bevacizumab help treat breast cancer that has spread or continues to grow despite being treated by other chemotherapy drugs before?
Read the detailed description
- Primary Objectives:
- To estimate the efficacy of every other week capecitabine and bevacizumab in patients with metastatic breast cancer in terms of overall response rate (complete response (CR) + partial response (PR)) when administered at the MTD of capecitabine determined by the phase I portion of this trial.
- Secondary Objectives:
- To estimate secondary efficacy endpoints of this combination including clinical benefit (CR+PR+SD > 6 months), time to tumor progression (TTP), progression free survival (TTP) and duration of response.
- To evaluate toxicity rates associated with this capecitabine schedule in combination with bevacizumab using the NCI CTC (version 3) and the Hand-Foot Syndrome Grading Scale developed by Roche Laboratories, Inc.
- To evaluate the pharmacogenetics of capecitabine in breast cancer patients by assessing the impact of specific candidate SNPs on toxicity and/or response.
- Conditions
- Breast Cancer
- Being tested
- Capecitabine, Bevacizumab
- Keywords
- Breast cancer, Metastatic breast cancer, Breast, Metastatic
- 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.
CapecitabineDrug
BevacizumabDrug
| Study group | Role | What they receive |
|---|---|---|
| 1 Capecitabine and Bevacizumab | Experimental | The Phase II trial has a Simon mini-max two-stage design. Twenty-seven patients will be enrolled to the first stage of the Phase II trial, with a target accrual of 40 patients. The treatment dose of capecitabine as determined in the Phase I portion of this trial will be administered orally in two divided doses daily on Days 1 through 7 and Days 15 through 21 in a 28 day cycle. Phase II patients will receive bevacizumab 10 mg/kg intravenously every 2 weeks concurrently with oral capecitabine. Patients will be evaluated for toxicity between Days 3 to 5 (complete blood count only), Day 8, Day 15, and Day 22 during cycle #1. Thereafter, toxicity will be assessed on Days 1 and 15. Efficacy will be assessed with every other week physical examination and radiographic scans of measurable disease every 12 weeks. Receives: Drug: Capecitabine; Drug: Bevacizumab |
What is being measured
The primary outcome is the main question the study is designed to answer.
Overall Objective Response
This is defined as the percentage of patients who achieve either an objective complete or partial target lesion response that is confirmed based on the RECIST criteria.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted3 May 2007 (estimated)
- Study startJun 2005
- Primary completionApr 2011
- Study completionApr 2011
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 Memorial Sloan Kettering Cancer CenterThe 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 1/2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 62 participants (actual)
Sponsor and investigators
- Lead sponsor
- Memorial Sloan Kettering Cancer Center
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tiffany Traina, MD, Principal investigator, Memorial Sloan Kettering Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00468585
- Sponsor's protocol ID
- 05-030
- Status last verified
- Dec 2015
- First submitted
- 2 May 2007
- Last updated
- 22 Jan 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 22 Jan 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Multicenter, Phase I/II Study of Every Other Week Capecitabine Dosing With Bevacizumab for the Treatment of Metastatic Breast Cancer Based Upon the Norton-Simon Mathematical Model
- ClinicalTrials.gov ID
- NCT00468585
- Acronym / sponsor ID
- 05-030
- Conditions
- Breast Cancer
- Keywords
- Breast cancer, Metastatic breast cancer, Breast, Metastatic
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 62 participants (actual)
- Lead sponsor
- Memorial Sloan Kettering Cancer CenterUniversity, hospital or other
- Study start
- Jun 2005
- Primary completion
- Apr 2011 (actual)
- Study completion
- Apr 2011 (actual)
- First posted
- 3 May 2007 (estimated)
- Results
- Posted 22 Jan 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The purpose of this study is to find out what effects (both good and bad) that capecitabine has on you and your breast cancer when given in a novel schedule in combination with the antibody therapy, bevacizumab. Capecitabine (Xeloda®) is an anticancer drug that was approved by FDA in 1998 for treating metastatic breast cancer. Capecitabine is a pill that blocks the way cancer cells multiply and grow. Usually, this medicine is taken twice a day for fourteen days in a row.
Patients then get a break from the drug for seven days. With this schedule and usual dose, some patients on capecitabine have experienced side effects that interfered with their daily comfort.Different doses and schedules of capecitabine have been studied in animal studies and in people with colon cancer. Mathematic modeling has been used to better understand these results.Information from these experiments leads us to ask if 7 days of treatment with capecitabine followed by a 7-day break is both safer and more active against breast cancer. The study you are considering is a first step in this direction and is designed to demonstrate both safety and activity.
Bevacizumab is a biologic therapy that targets the growth of blood vessels which tumors need to grow. Women whose breast cancer spread to other parts of their bodies lived longer without their cancers growing when they were treated with bevacizumab and chemotherapy. Bevacizumab was tested with the 14-day/7-day schedule of capecitabine. These two medicines are safe when given together and seem to work better against breast cancer than capecitabine alone.
This study is designed to answer the questions:
- What are the side effects of bevacizumab and capecitabine when given in this different schedule and how often do they occur?
- When given in this schedule, does capecitabine with bevacizumab help treat breast cancer that has spread or continues to grow despite being treated by other chemotherapy drugs before?
Detailed description
- Primary Objectives:
- To estimate the efficacy of every other week capecitabine and bevacizumab in patients with metastatic breast cancer in terms of overall response rate (complete response (CR) + partial response (PR)) when administered at the MTD of capecitabine determined by the phase I portion of this trial.
- Secondary Objectives:
- To estimate secondary efficacy endpoints of this combination including clinical benefit (CR+PR+SD > 6 months), time to tumor progression (TTP), progression free survival (TTP) and duration of response.
- To evaluate toxicity rates associated with this capecitabine schedule in combination with bevacizumab using the NCI CTC (version 3) and the Hand-Foot Syndrome Grading Scale developed by Roche Laboratories, Inc.
- To evaluate the pharmacogenetics of capecitabine in breast cancer patients by assessing the impact of specific candidate SNPs on toxicity and/or response.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| 1 Capecitabine and Bevacizumab | Experimental | Drug: Capecitabine, Drug: BevacizumabThe Phase II trial has a Simon mini-max two-stage design. Twenty-seven patients will be enrolled to the first stage of the Phase II trial, with a target accrual of 40 patients. The treatment dose of capecitabine as determined in the Phase I portion of this trial will be administered orally in two divided doses daily on Days 1 through 7 and Days 15 through 21 in a 28 day cycle. Phase II patients will receive bevacizumab 10 mg/kg intravenously every 2 weeks concurrently with oral capecitabine. Patients will be evaluated for toxicity between Days 3 to 5 (complete blood count only), Day 8, Day 15, and Day 22 during cycle #1. Thereafter, toxicity will be assessed on Days 1 and 15. Efficacy will be assessed with every other week physical examination and radiographic scans of measurable disease every 12 weeks. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Patient (male or female) with diagnosis of invasive adenocarcinoma of the breast confirmed at MSKCC either by histology or cytology.
- Clinical evidence of metastatic breast cancer, non-amenable to surgery or radiation therapy with curative intent.
- Presence of at least one measurable metastatic lesion according to the RECIST criteria which has not been irradiated (i.e. newly arising lesions in previously irradiated areas are accepted). Ascites, pleural effusion, and bone metastases are not considered measurable. Minimum indicator lesion size: greater than or equal to 10 mm measured by spiral CT or greater than or equal to 20 mm measured by conventional techniques.
- Any number of prior endocrine or biologic therapies is permitted on this trial. In addition, patients may be untreated in the metastatic setting or have received any number of prior cytotoxic regimens. All previous chemotherapy must have been discontinued at least 3 weeks prior to study entry. All acute toxic effects (excluding alopecia or neurotoxicity) of any prior therapy must have resolved to NCI CTC (Version 3) Grade less than or equal to 1.
- Endocrine therapy with an aromatase inhibitor, SERM (ie, tamoxifen) or fulvestrant is permitted within 4 weeks of study entry, however concurrent therapy with these drugs is not acceptable.
Key exclusion criteria (25 listed)
- Pregnant or nursing women may not participate. Patients of reproductive potential may not participate unless they have agreed to use an effective method of contraception and to continue contraception for 30 days from the date of the last study drug administration. Postmenopausal woman must be amenorrheic for at least 12 months to be considered of nonchildbearing potential.
- Life expectancy < 3 months.
- Serious, uncontrolled, concurrent infection.
- Any prior fluoropyrimidine therapy with the exception of adjuvant administration. Adjuvant fluoropyrimidine containing therapy must be completed at least 6 months prior to enrollment.
- Prior severe reaction to fluoropyrimidine therapy, or known hypersensitivity to 5-fluorouracil. A history of DPD deficiency will exclude patients from the trial.
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 |
|---|---|---|
| Capecitabine | Drug | 1 Capecitabine and Bevacizumab |
| Bevacizumab | Drug | 1 Capecitabine and Bevacizumab |
Primary outcome
Overall Objective Response
Time frame: 2 years
This is defined as the percentage of patients who achieve either an objective complete or partial target lesion response that is confirmed based on the RECIST criteria.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jan 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Related InfoLink 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.
Tiffany Traina, MD principal investigator
Memorial Sloan Kettering Cancer Center
5 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Capecitabine and Bevacizumab in people with Breast Cancer, run by Memorial Sloan Kettering Cancer Center at 5 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 16 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: finished, as of the sponsor's last update on 22 Jan 2016. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 5 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 combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 22 Jan 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?
Overall Objective Response (time frame: 2 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 22 Jan 2016.