Metastatic Breast CancerPhase 1NCT00496665
ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer
A Phase 1 study testing Vandetanib, Cyclophosphamide and Methotrexate in people with Metastatic Breast Cancer, run by Dana-Farber Cancer Institute at 2 sites in United States.
Trial summary
The purpose of this research study is to determine the safety and tolerability of the combination of Zactima with metronomic chemotherapy. Zactima is an oral anti-angiogenesis drug, which means it fights cancer by cutting off a tumor's blood supply. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Breast Cancer
- What is being tested?
- Vandetanib, Cyclophosphamide and Methotrexate
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 2 sitesUnited States
- Study dates
- Jul 2007to Mar 2009
- Phase
- Phase 1
- Are there results?
- None posted in the registry
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
- Patients must have histologically or cytologically confirmed Stage IV breast cancer
- Patients may have prior treatment with 0-4 prior chemotherapeutic regimens for metastatic disease.
- 18 years of age and older
- Life expectancy of greater than 3 months as assessed by patient's primary oncologist
- ECOG Performance Status of 0-2.
- LVEF > 45%, as assessed by echocardiogram or nuclear medicine gate study within 30 days prior to initiating protocol-based treatment
- Negative Serum pregnancy test
- No receipt of any investigational agents within 30 days prior to commencing study treatment
Who cannot join
- Abnormal laboratory results as outlined in the protocol
- Therapeutic anti-coagulation. The use of low dose warfarin, intermittent doses of TPA, or heparin flushes to prophylax against central venous catheter associated clots is acceptable.
- Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry and stable without steroid treatment for one week. Leptomeningeal disease is not eligible.
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate
- Clinically significant cardiac event such as myocardial infarction; NYHA classification of heart disease greater than or equal to 2; or presence of cardiac disease that increases the risk of ventricular arrhythmia
- History of arrhythmia which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia
Show all 17Show fewer
- Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication
- Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age
- Presence of left bundle branch block
- QTc with Bazett's correction that is unmeasurable or greater than 480msec on screening ECG.
- Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
- Hypertension not controlled by medical therapy
- Currently active diarrhea that may affect the ability of the patient to absorb the Zactima or tolerate diarrhea
- Previous or current non-breast malignancies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
- Major surgery within 4 weeks, or incompletely healed surgical incision before starting study therapy
- Patients with large or rapidly accumulating pleural or abdominal effusions
- Women who are currently pregnant or breastfeeding
Trial locations and contacts
2 sites in 1 country.
United States2 sites
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Massachusetts General Hospital
Boston, Massachusetts, 02215
About this study
Official title: A Phase I Study of ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer
The purpose of this research study is to determine the safety and tolerability of the combination of Zactima with metronomic chemotherapy. Zactima is an oral anti-angiogenesis drug, which means it fights cancer by cutting off a tumor's blood supply. Thus, the drug starves the tumor by preventing the delivery of nutrients and oxygen. Metronomic chemotherapy is low dose oral chemotherapy pills which are taken daily. Unlike traditional chemotherapy, metronomic chemotherapy is thought to fight cancer like Zactima, by cutting off the blood supply to tumors. Because the dose is very low, the side effects are generally mild and very different from those with higher dose chemotherapy given by vein.
Read the detailed description
- Each study cycle is 28 days long. Participants will take the study drug, Zactima, by mouth once a day. The dose of Zactima the participant will receive will be determined by the time when they enroll on the study. They will also take the metronomic chemotherapy by mouth. This consists of two drugs: cyclophosphamide and methotrexate. Cyclophosphamide is taken every day and methotrexate is taken on days 1 and 2 of each week.
- A physical exam will be performed on Day 1 of each cycle. Vital signs, including height, weight, blood pressure, and temperature will be done on Day 1 of each cycle, as well as at week 3 of Cycles 1 and 2.
- Electrocardiograms will be performed at various points to assess heart function. This will be done at week 1, 3, 5, 7, and 9, and then every 3 months for the rest of the study.
- Routine blood tests will be done on Day 1 of each cycle, as well as at week 3 for the first two cycles. Urine tests will be done on Day 1 of each cycle.
- An ultrasound will be done at Brigham and Women's Hospital in the Department of Vascular Medicine at week 3 and week 7.
- Participants will have scans done to assess their tumor every 2 cycles (8 weeks). These may include a CT scan, MRI, PET scan, x-rays, and/or bone scans.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Vandetanib, Cyclophosphamide, Methotrexate
- Keywords
- Stage IV breast cancer, metronomic chemotherapy
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
VandetanibDrug
Also called Zactima, ZD6474
Taken orally once a day in 28-day cycles (the dose will vary)
CyclophosphamideDrug
Metronic Chemotherapy: Low dose pills taken every day of each 28-day cycle
MethotrexateDrug
Metronic Chemotherapy: low dose pills taken on days 1 and 2 of each week
| Study group | Role | What they receive |
|---|---|---|
| Vandetenib | Experimental | Cyclophosphamide 50 mg daily, methotrexate 2.5 mg days 1-2 weekly, and daily vandetanib (zactima) in 3 dose-escalation cohorts (100mg=Cohort 1) (200mg=Cohort 2) (300mg=Cohort3) Receives: Drug: Vandetanib; Drug: Cyclophosphamide; Drug: Methotrexate |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the safety and tolerability of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy
Measured: 2 years
Secondary outcomes (1)
To determine the response rate of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy in patients with measurable disease.
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 posted4 Jul 2007 (estimated)
- Study startJul 2007
- Primary completionAug 2008
- Study completionMar 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic Breast CancerStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Erica Mayer, MD, MPH, Dana-Farber Cancer Institute
- Investigators
- Erica Mayer, MD, MPH, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00496665
- Sponsor's protocol ID
- 06-402
- Status last verified
- Nov 2013
- First submitted
- 3 Jul 2007
- Last updated
- 18 Nov 2013
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 18 Nov 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of ZD6474 (Zactima) and Metronomic Chemotherapy in Advanced Breast Cancer
- ClinicalTrials.gov ID
- NCT00496665
- Acronym / sponsor ID
- 06-402
- Conditions
- Metastatic Breast Cancer
- Keywords
- Stage IV breast cancer, metronomic chemotherapy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- AstraZeneca, Massachusetts General Hospital, Brigham and Women's Hospital
- Study start
- Jul 2007
- Primary completion
- Aug 2008 (actual)
- Study completion
- Mar 2009 (actual)
- First posted
- 4 Jul 2007 (estimated)
- Results
- Not posted in the source record
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 research study is to determine the safety and tolerability of the combination of Zactima with metronomic chemotherapy. Zactima is an oral anti-angiogenesis drug, which means it fights cancer by cutting off a tumor's blood supply. Thus, the drug starves the tumor by preventing the delivery of nutrients and oxygen. Metronomic chemotherapy is low dose oral chemotherapy pills which are taken daily. Unlike traditional chemotherapy, metronomic chemotherapy is thought to fight cancer like Zactima, by cutting off the blood supply to tumors. Because the dose is very low, the side effects are generally mild and very different from those with higher dose chemotherapy given by vein.
Detailed description
- Each study cycle is 28 days long. Participants will take the study drug, Zactima, by mouth once a day. The dose of Zactima the participant will receive will be determined by the time when they enroll on the study. They will also take the metronomic chemotherapy by mouth. This consists of two drugs: cyclophosphamide and methotrexate. Cyclophosphamide is taken every day and methotrexate is taken on days 1 and 2 of each week.
- A physical exam will be performed on Day 1 of each cycle. Vital signs, including height, weight, blood pressure, and temperature will be done on Day 1 of each cycle, as well as at week 3 of Cycles 1 and 2.
- Electrocardiograms will be performed at various points to assess heart function. This will be done at week 1, 3, 5, 7, and 9, and then every 3 months for the rest of the study.
- Routine blood tests will be done on Day 1 of each cycle, as well as at week 3 for the first two cycles. Urine tests will be done on Day 1 of each cycle.
- An ultrasound will be done at Brigham and Women's Hospital in the Department of Vascular Medicine at week 3 and week 7.
- Participants will have scans done to assess their tumor every 2 cycles (8 weeks). These may include a CT scan, MRI, PET scan, x-rays, and/or bone scans.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Vandetenib | Experimental | Drug: Vandetanib, Drug: Cyclophosphamide, Drug: MethotrexateCyclophosphamide 50 mg daily, methotrexate 2.5 mg days 1-2 weekly, and daily vandetanib (zactima) in 3 dose-escalation cohorts (100mg=Cohort 1) (200mg=Cohort 2) (300mg=Cohort3) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Patients must have histologically or cytologically confirmed Stage IV breast cancer
- Patients may have prior treatment with 0-4 prior chemotherapeutic regimens for metastatic disease.
- 18 years of age and older
- Life expectancy of greater than 3 months as assessed by patient's primary oncologist
- ECOG Performance Status of 0-2.
Key exclusion criteria (17 listed)
- Abnormal laboratory results as outlined in the protocol
- Therapeutic anti-coagulation. The use of low dose warfarin, intermittent doses of TPA, or heparin flushes to prophylax against central venous catheter associated clots is acceptable.
- Brain metastases or spinal cord compression, unless treated at least 4 weeks before entry and stable without steroid treatment for one week. Leptomeningeal disease is not eligible.
- Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate
- Clinically significant cardiac event such as myocardial infarction; NYHA classification of heart disease greater than or equal to 2; or presence of cardiac disease that increases the risk of ventricular arrhythmia
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 |
|---|---|---|
| VandetanibAlso: Zactima, ZD6474Taken orally once a day in 28-day cycles (the dose will vary) | Drug | Vandetenib |
| CyclophosphamideMetronic Chemotherapy: Low dose pills taken every day of each 28-day cycle | Drug | Vandetenib |
| MethotrexateMetronic Chemotherapy: low dose pills taken on days 1 and 2 of each week | Drug | Vandetenib |
Primary outcome
To determine the safety and tolerability of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy
Time frame: 2 years
1 secondary outcome
To determine the response rate of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy in patients with measurable disease.
Time frame: 2 years
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Nov 2013.
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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.
Erica Mayer, MD, MPH principal investigator
Dana-Farber Cancer Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Vandetanib, Cyclophosphamide and Methotrexate in people with Metastatic Breast Cancer, run by Dana-Farber Cancer Institute at 2 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 8 inclusion and 17 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 18 Nov 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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 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.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
To determine the safety and tolerability of combination therapy with ZD6474 (Zactima) and metronomic chemotherapy (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 18 Nov 2013.