Metastatic Breast CancerPhase 1NCT00169000
Safety Study of a New Schedule of Capecitabine and Docetaxel to Treat Cancers
A Phase 1 study testing Capecitabine and Docetaxel in people with Metastatic Breast Cancer, run by Dartmouth-Hitchcock Medical Center at 1 site in United States.
Trial summary
The combination of capecitabine and docetaxel is given to treat several different types of cancer. Capecitabine is usually given by mouth for 14 days, and docetaxel is given IV on the first day of capecitabine. 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?
- Capecitabine and Docetaxel
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 12 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2003to Mar 2006
- 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 with a histologically or cytologically proven metastatic solid tumor.
- Patients with measurable disease or an evaluable bone lesion that will not undergo biopsy.
- Patients treated within the additional cohort at MTD will have metastatic breast cancer with a site of disease that is amenable to percutaneous FNA and must be willing to undergo serial FNA biopsies of their primary tumor.
- Age > 18 years.
- Life expectancy of at least 6 months.
- ECOG performance status 0-2.
- Adequate hematologic, hepatic, and renal function
- Patients must have an intact upper gastrointestinal tract, be able to swallow tablets, and not have a malabsorption syndrome.
Who cannot join
- No significant uncontrolled infectious or cardiovascular disease, or a myocardial infarction within the prior 12 months.
- No prior organ allograft.
- No prior treatment with capecitabine or with docetaxel.
- No prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil.
- No concurrent antacid therapy is allowed.
- No other significant medical/surgical diseases.
Trial locations and contacts
1 site in 1 country.
United States1 site
Norris Cotton Cancer Center
Lebanon, New Hampshire, 03756
About this study
Official title: Phase I Study of a Novel Schedule of Capecitabine and Docetaxel in Patients With Advanced Solid Tumors
The combination of capecitabine and docetaxel is given to treat several different types of cancer. Capecitabine is usually given by mouth for 14 days, and docetaxel is given IV on the first day of capecitabine. The effects of changes in the schedule of the combination of docetaxel and capecitabine has been examined in human breast cancer cells. A capecitabine by-product was given orally to breast cancer-bearing animals for 14 consecutive days. Docetaxel was given IV at a variety of times between days 1 and 15. The greatest reductions in the volume of the cancer were seen when animals were treated with docetaxel between days 6 and 10. In two other breast cancer models, the maximal degree of delay in growth of the tumors was achieved when the animals were treated with docetaxel on day 8 of a 14 day course of capecitabine. The extent of tumor response was not explained by changes in tumor levels of the enzyme thymidine phosphorylase, which is thought to be the mechanism behind the interaction of capecitabine and docetaxel. In the breast cancer cells, capecitabine increases the level of proteins which promote death of cancer cells, and it inhibits the levels of proteins which block death of cancer cells.
Our hypothesis is that capecitabine and docetaxel interact with each other, because capecitabine primes the pro-death machinery of the cell by increasing the ratio of death-promoting proteins to death-inhibiting proteins. Cells are more susceptible to killing by docetaxel when the pro-death machinery is activated by capecitabine.
This is a safety study to find the highest dose of capecitabine that can be given safely for 14 days, in combination with docetaxel given at a fixed dose on day 8. Once this dose of capecitabine has been determined, an additional nine patients with tumors that can be biopsied will be treated at this dose, and levels of capecitabine, its byproducts, and docetaxel will be measured in the bloodstream. Biopsies of tumors will also be taken before and after the docetaxel is given, and the levels of pro-death and anti-death proteins will be measured.
Read the detailed description
This is a phase I study using an accelerated titration design to determine the maximum tolerated dose (MTD) of capecitabine given orally on a BID schedule from days 1-14, in combination with docetaxel given at a fixed dose of 75 mg/m2 IV on day 8. Once the MTD of capecitabine has been determined, an additional nine patients with accessible tumors will be treated at the MTD. Pharmacokinetics of plasma capecitabine, 5-FU, 5'-deoxy-5-fluorouridine, and docetaxel will be assayed in these nine patients, and tumor biopsies will be taken to assess Bax:Bcl-2 ratios and Bcl-2 phosphorylation at several time points. The primary aim of this study will be to determine the maximum tolerated dose and dose limiting toxicities of capecitabine when given with a fixed dose of docetaxel on day 8 of a 21 day schedule. Secondary aims will include assessment of the pharmacokinetics of capecitabine and docetaxel on this schedule, and determination of intratumoral Bax:Bcl-2, Bcl-2 phosphorylation, and DPD expression, and correlation with clinical toxicities and antitumor response.
- Conditions
- Metastatic Breast Cancer
- Being tested
- Capecitabine, Docetaxel
- Keywords
- breast cancer, capecitabine, docetaxel, pharmacokinetic/pharmacodynamic, bcl-2, bax
- Medical subject headings
- Breast Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CapecitabineDrug
Also called Xeloda
Capecitabine at the following dose levels for 14 days every 21 days, beginning with dose level 1
Dose level -2 600 mg/m2 po BID
Dose level -1 700 mg/m2 po BID
Dose level 1 825 mg/m2 po BID
Dose level 2 1000 mg/m2 po BID
DocetaxelDrug
Also called Taxotere
75 mg/m2 over one hour on day 8 of each cycle
| Study group | Role | What they receive |
|---|---|---|
| Capecitabine and Docetaxel | Experimental | Escalating doses of capecitabine days 1-14 with a fixed dose of docetaxel on Day 8 of a 21 day cycle Receives: Drug: Capecitabine; Drug: Docetaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
To determine the maximum tolerated dose, and dose limiting toxicity of capecitabine when given daily for 14 days with docetaxel given on day 8 of a 21 day cycle
Measured: 3 weeks
Secondary outcomes (3)
To determine the pharmacokinetic profile of capecitabine, 5-fluorouracil, and 5'-deoxy-5-fluorouridine following administration of docetaxel on day 8.
Measured: 9 days
To determine the expression of Bax, Bcl-2, and phosphorylated Bcl-2 at baseline and again on days 8 and 9 of capecitabine when given at the MTD
Measured: 9 days
To define pharmacodynamic relationships between observed changes in dihydropyrimidine dehydrogenase (DPD) and altered expression of Bax and Bcl-2 with clinical toxicities and antitumor response
Measured: 9 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted15 Sep 2005 (estimated)
- Study startJan 2003
- Primary completionSep 2005
- Study completionMar 2006
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 Dartmouth-Hitchcock Medical 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
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 12 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dartmouth-Hitchcock Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- Hoffmann-La Roche
- Investigators
- Gary N Schwartz, MD, Study chair, Norris Cotton Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00169000
- Sponsor's protocol ID
- D-0139
- Status last verified
- Aug 2009
- First submitted
- 9 Sep 2005
- Last updated
- 6 Aug 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 6 Aug 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase I Study of a Novel Schedule of Capecitabine and Docetaxel in Patients With Advanced Solid Tumors
- ClinicalTrials.gov ID
- NCT00169000
- Acronym / sponsor ID
- D-0139
- Conditions
- Metastatic Breast Cancer
- Keywords
- breast cancer, capecitabine, docetaxel, pharmacokinetic/pharmacodynamic, bcl-2, bax
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 12 participants (actual)
- Lead sponsor
- Dartmouth-Hitchcock Medical CenterUniversity, hospital or other
- Collaborators
- Hoffmann-La Roche
- Study start
- Jan 2003
- Primary completion
- Sep 2005 (actual)
- Study completion
- Mar 2006 (actual)
- First posted
- 15 Sep 2005 (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 combination of capecitabine and docetaxel is given to treat several different types of cancer. Capecitabine is usually given by mouth for 14 days, and docetaxel is given IV on the first day of capecitabine. The effects of changes in the schedule of the combination of docetaxel and capecitabine has been examined in human breast cancer cells. A capecitabine by-product was given orally to breast cancer-bearing animals for 14 consecutive days. Docetaxel was given IV at a variety of times between days 1 and 15. The greatest reductions in the volume of the cancer were seen when animals were treated with docetaxel between days 6 and 10. In two other breast cancer models, the maximal degree of delay in growth of the tumors was achieved when the animals were treated with docetaxel on day 8 of a 14 day course of capecitabine. The extent of tumor response was not explained by changes in tumor levels of the enzyme thymidine phosphorylase, which is thought to be the mechanism behind the interaction of capecitabine and docetaxel. In the breast cancer cells, capecitabine increases the level of proteins which promote death of cancer cells, and it inhibits the levels of proteins which block death of cancer cells.
Our hypothesis is that capecitabine and docetaxel interact with each other, because capecitabine primes the pro-death machinery of the cell by increasing the ratio of death-promoting proteins to death-inhibiting proteins. Cells are more susceptible to killing by docetaxel when the pro-death machinery is activated by capecitabine.
This is a safety study to find the highest dose of capecitabine that can be given safely for 14 days, in combination with docetaxel given at a fixed dose on day 8. Once this dose of capecitabine has been determined, an additional nine patients with tumors that can be biopsied will be treated at this dose, and levels of capecitabine, its byproducts, and docetaxel will be measured in the bloodstream. Biopsies of tumors will also be taken before and after the docetaxel is given, and the levels of pro-death and anti-death proteins will be measured.
Detailed description
This is a phase I study using an accelerated titration design to determine the maximum tolerated dose (MTD) of capecitabine given orally on a BID schedule from days 1-14, in combination with docetaxel given at a fixed dose of 75 mg/m2 IV on day 8. Once the MTD of capecitabine has been determined, an additional nine patients with accessible tumors will be treated at the MTD. Pharmacokinetics of plasma capecitabine, 5-FU, 5'-deoxy-5-fluorouridine, and docetaxel will be assayed in these nine patients, and tumor biopsies will be taken to assess Bax:Bcl-2 ratios and Bcl-2 phosphorylation at several time points. The primary aim of this study will be to determine the maximum tolerated dose and dose limiting toxicities of capecitabine when given with a fixed dose of docetaxel on day 8 of a 21 day schedule. Secondary aims will include assessment of the pharmacokinetics of capecitabine and docetaxel on this schedule, and determination of intratumoral Bax:Bcl-2, Bcl-2 phosphorylation, and DPD expression, and correlation with clinical toxicities and antitumor response.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Capecitabine and Docetaxel | Experimental | Drug: Capecitabine, Drug: DocetaxelEscalating doses of capecitabine days 1-14 with a fixed dose of docetaxel on Day 8 of a 21 day cycle |
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 with a histologically or cytologically proven metastatic solid tumor.
- Patients with measurable disease or an evaluable bone lesion that will not undergo biopsy.
- Patients treated within the additional cohort at MTD will have metastatic breast cancer with a site of disease that is amenable to percutaneous FNA and must be willing to undergo serial FNA biopsies of their primary tumor.
- Age > 18 years.
- Life expectancy of at least 6 months.
Key exclusion criteria (6 listed)
- No significant uncontrolled infectious or cardiovascular disease, or a myocardial infarction within the prior 12 months.
- No prior organ allograft.
- No prior treatment with capecitabine or with docetaxel.
- No prior unanticipated severe reaction to fluoropyrimidine therapy or known hypersensitivity to 5-fluorouracil.
- No concurrent antacid therapy is allowed.
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 |
|---|---|---|
| CapecitabineAlso: XelodaCapecitabine at the following dose levels for 14 days every 21 days, beginning with dose level 1 Dose level -2 600 mg/m2 po BID Dose level -1 700 mg/m2 po BID Dose level 1 825 mg/m2 po BID Dose level 2 1000 mg/m2 po BID | Drug | Capecitabine and Docetaxel |
| DocetaxelAlso: Taxotere75 mg/m2 over one hour on day 8 of each cycle | Drug | Capecitabine and Docetaxel |
Primary outcome
To determine the maximum tolerated dose, and dose limiting toxicity of capecitabine when given daily for 14 days with docetaxel given on day 8 of a 21 day cycle
Time frame: 3 weeks
3 secondary outcomes
To determine the pharmacokinetic profile of capecitabine, 5-fluorouracil, and 5'-deoxy-5-fluorouridine following administration of docetaxel on day 8.
Time frame: 9 days
To determine the expression of Bax, Bcl-2, and phosphorylated Bcl-2 at baseline and again on days 8 and 9 of capecitabine when given at the MTD
Time frame: 9 days
To define pharmacodynamic relationships between observed changes in dihydropyrimidine dehydrogenase (DPD) and altered expression of Bax and Bcl-2 with clinical toxicities and antitumor response
Time frame: 9 days
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 6 Aug 2009.
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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.
Gary N Schwartz, MD study chair
Norris Cotton Cancer Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Capecitabine and Docetaxel in people with Metastatic Breast Cancer, run by Dartmouth-Hitchcock Medical Center 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 8 inclusion and 6 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 6 Aug 2009. 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 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 maximum tolerated dose, and dose limiting toxicity of capecitabine when given daily for 14 days with docetaxel given on day 8 of a 21 day cycle (time frame: 3 weeks). 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 6 Aug 2009.