Extrahepatic Bile Duct CancerPhase 1NCT00486356
Capecitabine, Epirubicin, and Carboplatin in Treating Patients With Progressive, Unresectable, or Metastatic Cancer
A Phase 1 study testing capecitabine, carboplatin and epirubicin hydrochloride in people with Extrahepatic Bile Duct Cancer and Gallbladder Cancer, run by University of Nebraska at 1 site in United States.
Trial summary
RATIONALE: Drugs used in chemotherapy, such as capecitabine, epirubicin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells. Read more about this study
- Who is it for?
- Ages 18 to 120 years
- Conditions the study is for
- Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Gastric Cancer
- What is being tested?
- capecitabine, carboplatin and epirubicin hydrochloride
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 46 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Oct 2004to 1 Jan 2010
- 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 to 120 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Pathologically confirmed cancer, meeting 1 of the following criteria:
- Disease that has progressed on standard therapy
- Locally advanced but unresectable primary or recurrent solid tumor
- Metastatic disease, including previously untreated metastatic disease for which study regimen represents reasonable initial chemotherapy with palliative intent (e.g., metastatic gastric cancer, hepatobiliary cancer, or cancer for which no effective standard therapy exists)
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count ≥ 2,000/mm³
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- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
- alanine aminotransferase (ALT) \& aspartate aminotransferase (AST) ≤ 2.5 times ULN
- Creatinine ≤ 1.6 mg/dL
- Left ventricular ejection fraction ≥ 50%
- Fertile patients must use effective contraception
- Recovered from prior therapy
- More than 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) or immunotherapy
- At least 2 weeks since prior radiotherapy
- At least 8 weeks since prior strontium therapy
- At least 4 weeks since prior and no concurrent sorivudine or brivudine
Who cannot join
- No other potentially curative treatment options available (e.g., surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy)
- No leukemia or lymphoma
- No primary central nervous system (CNS) malignancies or CNS metastases
- No other medical illness that would preclude study treatment
- No active infection requiring IV antibiotic therapy unless the infection has resolved
- No history of allergy to platinum compounds, mannitol, or to antiemetics appropriate for administration in conjunction with protocol-directed chemotherapy
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- No history of unexpectedly severe intolerance to fluorouracil
- Not pregnant or nursing/negative pregnancy test
- No prior doxorubicin at cumulative doses > 300 mg/m²
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No concurrent cimetidine
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Nebraska Medical Center, Eppley Cancer Center
Omaha, Nebraska, 68198-6805
About this study
Official title: A Phase I Trial of Epirubicin, Carboplatin and Capecitabine in Adult Cancer Patients
RATIONALE: Drugs used in chemotherapy, such as capecitabine, epirubicin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer.
Read the detailed description
OBJECTIVES:
Primary
- Determine the recommended phase II dose of capecitabine when given together with epirubicin hydrochloride and carboplatin in patients with progressive, unresectable, or metastatic cancer.
- Determine the toxicities of this regimen in these patients.
Secondary
- Correlate end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dose and clinical toxicity in these patients.
- Correlate the pharmacokinetics of capecitabine with clinical toxicity in these patients.
- Determine the possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity in these patients.
- Document antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive epirubicin hydrochloride IV over 2 hours and carboplatin IV over 30 minutes on day 1 and oral capecitabine twice daily on days 2-5, 8-12, and 15-19. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Peripheral blood is collected for pharmacokinetic and pharmacogenetic studies before beginning study treatment and periodically during study. Samples for the pharmacogenetic studies are analyzed for correlation between polymorphisms in the promoter region of the thymidylate synthase gene and clinical toxicity. Patients also undergo bone marrow aspirate before beginning study treatment for molecular profiling studies.
- Conditions
- Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Gastric Cancer, Liver Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Being tested
- capecitabine, carboplatin, epirubicin hydrochloride, microarray analysis, polymorphism analysis
- Keywords
- unspecified adult solid tumor, protocol specific, recurrent gastric cancer, stage IV gastric cancer, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer, recurrent extrahepatic bile duct cancer, unresectable extrahepatic bile duct cancer, recurrent gallbladder cancer, unresectable gallbladder cancer
- Medical subject headings
- Bile Duct Neoplasms, Gallbladder Neoplasms, Stomach Neoplasms, Liver Neoplasms, Carcinoma, Hepatocellular
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
capecitabineDrug
Also called Xeloda
carboplatinDrug
Also called Paraplatin
epirubicin hydrochlorideDrug
Also called Ellence
microarray analysisGenetic
polymorphism analysisGenetic
| Study group | Role | What they receive |
|---|---|---|
| Capecitabine, Epirubicin, and Carboplatin | Experimental | Determine the recommended phase II dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer. Receives: Drug: capecitabine; Drug: carboplatin; Drug: epirubicin hydrochloride; Genetic: microarray analysis; Genetic: polymorphism analysis; Other: pharmacological study |
What is being measured
The primary outcome is the main question the study is designed to answer.
Recommended phase II dose of capecitabine
Establish a recommended Phase II dose of oral capecitabine given twice daily on days 2-5, 8-12, and 15-19 in combination with fixed IV doses of epirubicin and carboplatin given day 1 of each 28-day cycle
Measured: Every 28-days until first documented progression up to 63 months
Toxicities of combined chemotherapy regimen
Evaluate all toxicities associated with this combination chemotherapy regimen: 1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening
Measured: Every 28-days until first documented progression up to 63 months
Secondary outcomes (4)
End-of-infusion levels of epirubicin hydrochloride/metabolites and incidence of correlation with epirubicin hydrochloride dosing and clinical toxicity
Correlation of end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dosing and clinical toxicity (1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening)
Measured: Each day of dosing up to 63 months
Correlation of the pharmacokinetics (speed of appearance in the blood plasma and its concentration) of capecitabine with clinical toxicity
Measure the pharmacokinetics of capecitabine and correlate these parameters with clinical toxicity
Measured: Each day of dosing up to 63 months
Incidence of Correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity
Assess possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity
Measured: Post-treatment up to 63 months
Antitumor activity
Document any anti-tumor activity (MTT assay is a quantitative and sensitive detection of cell proliferation as it measures the growth rate of cells by virtue of a linear relationship between cell activity and absorbance.)
Measured: Prior to cycle 1, and then every two 28 day cycles up to 63 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2007 (estimated)
- Study start1 Oct 2004
- Primary completion1 Jan 2010
- Study completion1 Jan 2010
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Extrahepatic Bile Duct CancerStudies of the same condition, open and under way.
- More trials run by University of NebraskaThe 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
- 46 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Nebraska
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Jean L Grem, MD, Principal investigator, University of Nebraska
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00486356
- Sponsor's protocol ID
- 0284-04-FB
- Other IDs
- P30CA036727
- Status last verified
- Dec 2023
- First submitted
- 13 Jun 2007
- Last updated
- 3 Jan 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 3 Jan 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Trial of Epirubicin, Carboplatin and Capecitabine in Adult Cancer Patients
- ClinicalTrials.gov ID
- NCT00486356
- Acronym / sponsor ID
- 0284-04-FB
- Conditions
- Extrahepatic Bile Duct Cancer, Gallbladder Cancer, Gastric Cancer, Liver Cancer, Unspecified Adult Solid Tumor, Protocol Specific
- Keywords
- unspecified adult solid tumor, protocol specific, recurrent gastric cancer, stage IV gastric cancer, advanced adult primary liver cancer, localized unresectable adult primary liver cancer, recurrent adult primary liver cancer, recurrent extrahepatic bile duct cancer, unresectable extrahepatic bile duct cancer
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 46 participants (actual)
- Lead sponsor
- University of NebraskaUniversity, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Study start
- 1 Oct 2004 (actual)
- Primary completion
- 1 Jan 2010 (actual)
- Study completion
- 1 Jan 2010 (actual)
- First posted
- 14 Jun 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.
RATIONALE: Drugs used in chemotherapy, such as capecitabine, epirubicin, and carboplatin, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving more than one drug (combination chemotherapy) may kill more tumor cells.
PURPOSE: This phase I trial is studying the side effects and best dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer.
Detailed description
OBJECTIVES:
Primary
- Determine the recommended phase II dose of capecitabine when given together with epirubicin hydrochloride and carboplatin in patients with progressive, unresectable, or metastatic cancer.
- Determine the toxicities of this regimen in these patients.
Secondary
- Correlate end-of-infusion levels of epirubicin hydrochloride and its metabolites with epirubicin hydrochloride dose and clinical toxicity in these patients.
- Correlate the pharmacokinetics of capecitabine with clinical toxicity in these patients.
- Determine the possible correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity in these patients.
- Document antitumor activity of this regimen in these patients.
OUTLINE: This is a dose-escalation study of capecitabine.
Patients receive epirubicin hydrochloride IV over 2 hours and carboplatin IV over 30 minutes on day 1 and oral capecitabine twice daily on days 2-5, 8-12, and 15-19. Treatment repeats every 28 days in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of capecitabine until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Peripheral blood is collected for pharmacokinetic and pharmacogenetic studies before beginning study treatment and periodically during study. Samples for the pharmacogenetic studies are analyzed for correlation between polymorphisms in the promoter region of the thymidylate synthase gene and clinical toxicity. Patients also undergo bone marrow aspirate before beginning study treatment for molecular profiling studies.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Capecitabine, Epirubicin, and Carboplatin | Experimental | Drug: capecitabine, Drug: carboplatin, Drug: epirubicin hydrochloride, Genetic: microarray analysis, Genetic: polymorphism analysis, Other: pharmacological studyDetermine the recommended phase II dose of capecitabine when given together with epirubicin and carboplatin in treating patients with progressive, unresectable, or metastatic cancer. |
Who may qualify
- Ages
- 18 to 120 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (17 listed)
- Pathologically confirmed cancer, meeting 1 of the following criteria:
- Eastern Cooperative Oncology Group (ECOG) performance status 0-2
- Absolute neutrophil count ≥ 2,000/mm³
- Platelet count ≥ 100,000/mm³
- Bilirubin ≤ 1.5 times upper limit of normal (ULN)
Key exclusion criteria (11 listed)
- No other potentially curative treatment options available (e.g., surgery, radiotherapy, chemoradiotherapy, or combination chemotherapy)
- No leukemia or lymphoma
- No primary central nervous system (CNS) malignancies or CNS metastases
- No other medical illness that would preclude study treatment
- No active infection requiring IV antibiotic therapy unless the infection has resolved
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: Xeloda | Drug | Capecitabine, Epirubicin, and Carboplatin |
| carboplatinAlso: Paraplatin | Drug | Capecitabine, Epirubicin, and Carboplatin |
| epirubicin hydrochlorideAlso: Ellence | Drug | Capecitabine, Epirubicin, and Carboplatin |
| microarray analysis | Genetic | Capecitabine, Epirubicin, and Carboplatin |
| polymorphism analysis | Genetic | Capecitabine, Epirubicin, and Carboplatin |
| pharmacological study | Other | Capecitabine, Epirubicin, and Carboplatin |
Primary outcome
Recommended phase II dose of capecitabine
Time frame: Every 28-days until first documented progression up to 63 months
Establish a recommended Phase II dose of oral capecitabine given twice daily on days 2-5, 8-12, and 15-19 in combination with fixed IV doses of epirubicin and carboplatin given day 1 of each 28-day cycle
Toxicities of combined chemotherapy regimen
Time frame: Every 28-days until first documented progression up to 63 months
Evaluate all toxicities associated with this combination chemotherapy regimen: 1 - mild, 2 - moderate, 3 = severe and 4 - life-threatening
4 secondary outcomes
End-of-infusion levels of epirubicin hydrochloride/metabolites and incidence of correlation with epirubicin hydrochloride dosing and clinical toxicity
Time frame: Each day of dosing up to 63 months
Correlation of the pharmacokinetics (speed of appearance in the blood plasma and its concentration) of capecitabine with clinical toxicity
Time frame: Each day of dosing up to 63 months
Incidence of Correlation between polymorphisms in the promoter region of the thymidylate synthase gene with clinical toxicity
Time frame: Post-treatment up to 63 months
Antitumor activity
Time frame: Prior to cycle 1, and then every two 28 day cycles up to 63 months
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 3 Jan 2024.
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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.
Jean L Grem, MD principal investigator
University of Nebraska
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, carboplatin and epirubicin hydrochloride in people with Extrahepatic Bile Duct Cancer and Gallbladder Cancer, run by University of Nebraska 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 17 inclusion and 11 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 3 Jan 2024. 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?
Recommended phase II dose of capecitabine (time frame: Every 28-days until first documented progression up to 63 months). The study lists 2 primary outcomes in all. 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 3 Jan 2024.