Adenocarcinoma of the Extrahepatic Bile DuctPhase 2NCT00085410
Bortezomib in Treating Patients With Unresectable Locally Advanced or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder
A Phase 2 study testing bortezomib in people with Adenocarcinoma of the Extrahepatic Bile Duct and Adenocarcinoma of the Gallbladder, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase II trial is studying how well bortezomib works as first-line systemic therapy in treating patients with unresectable locally advanced or metastatic adenocarcinoma (cancer) of the bile duct or gallbladder. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Adenocarcinoma of the Extrahepatic Bile Duct, Adenocarcinoma of the Gallbladder, Advanced Adult Primary Liver Cancer
- What is being tested?
- bortezomib
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2004to Apr 2010
- 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 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Absolute neutrophil count >= 1,500/mm3
- No psychiatric illness or social situation that would preclude study compliance
- Chemotherapy administered solely as a radiosensitizer or as adjuvant therapy and investigational or targeted therapies (i.e., inhibitors of the epidermal growth factor receptor) will not count toward the maximum of 2 prior regimens allowed
- Histologically or cytologically confirmed adenocarcinoma of the intrahepatic or extrahepatic bile duct or gallbladder:
- Locally advanced or metastatic disease
- At least 1 unidimensionally measurable lesion >=20 mm by conventional techniques OR >= 10 mm by spiral CT scan
Show all 34Show fewer
- Not amenable to curative surgical resection
- No known brain metastases
- Performance status:
- ECOG 0-2
- Life expectancy:
- More than 12 weeks
- Platelet count >= 100,000/mm3
- WBC >= 3,000/mm3
- AST and ALT ≤ 2.5 times upper limit of normal (ULN) [Note: Biliary shunting or stenting allowed to achieve the required bilirubin and transaminase levels]
- Bilirubin ≤ 1.5 times ULN [Note: Biliary shunting or stenting allowed to achieve the required bilirubin and transaminase levels]
- Creatinine within ULN OR Creatinine clearance >= 60 mL/min
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No symptomatic cardiac arrhythmia within the past 4 weeks
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No underlying neuropathy >= grade 2
- No history of allergic reaction to boron, mannitol, or bortezomib
- No active or ongoing infection
- No concurrent uncontrolled illness
- No medical or psychiatric condition that would preclude study participation
- No prophylactic granulocyte or platelet growth factors (filgrastim [G-CSF] or sargramostim [GM-CSF])
- Prior chemotherapy as a radiosensitizer (e.g., fluorouracil or gemcitabine) with radiotherapy is allowed as adjuvant therapy after resection for locally advanced disease provided there is evidence of disease progression
- No more than 2 prior chemotherapy regimens for locally advanced or metastatic disease
- No concurrent combination antiretroviral therapy for HIV-positive patients
- No other concurrent anticancer agents or therapies
- No other concurrent investigational agents
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Fox Chase Cancer Center
Philadelphia, Pennsylvania, 19111-2497
About this study
Official title: Phase II and Pharmacodynamic Study of PS-341 in Patients With Unresectable or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder
This phase II trial is studying how well bortezomib works as first-line systemic therapy in treating patients with unresectable locally advanced or metastatic adenocarcinoma (cancer) of the bile duct or gallbladder. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the objective response rate in patients with unresectable locally advanced or metastatic adenocarcinoma of the bile duct or gallbladder treated with bortezomib.
SECONDARY OBJECTIVES:
- Determine the time to disease progression in patients treated with this drug.
II. Determine the overall survival of patients treated with this drug. III. Correlate the degree of proteasome inhibition in peripheral blood with degree of proteasome inhibition in tumor specimens of patients treated with this drug.
IV. Correlate phenotypic expression of NF-kB, p53, and other molecular markers in biliary washings and tumor biopsies with clinical outcomes in patients treated with this drug.
- Correlate treatment with this drug with changes in phenotypic expression of molecular markers in these patients.
OUTLINE: This is an open-label, multicenter study.
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year.
- Conditions
- Adenocarcinoma of the Extrahepatic Bile Duct, Adenocarcinoma of the Gallbladder, Advanced Adult Primary Liver Cancer, Gastrointestinal Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- Being tested
- bortezomib
- Medical subject headings
- Gastrointestinal Neoplasms, Carcinoma, Hepatocellular, Bile Duct Neoplasms, Gallbladder Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Given IV
| Study group | Role | What they receive |
|---|---|---|
| Arm I | Experimental | Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Receives: Drug: bortezomib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective Response Rate
Objective Response Rate (ORR) was determined by best response on radiologic assessment (computed tomography or magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.
Measured: Up to 1 year
Secondary outcomes (5)
Time to Disease Progression
Time from initiation of therapy to first progressive disease.
Measured: Up to 1 year
Overall Survival
The time from initiation of therapy to death or last follow-up.
Measured: Up to 1 year
Correlation of the Degree of Proteasome Inhibition in Peripheral Blood With the Degree of Proteasome Inhibition in Tumor Specimens
Proteasome inhibition compared between tumor specimens and peripheral blood. Sufficient tissue samples are required for this analysis.
Measured: Once in the screening period (within 14 days of starting treatment)
Correlation of Phenotypic Expression of NF-kB, p53, and Other Molecular Markers in Biliary Washings and Tumor Biopsies With Clinical Outcomes
Evaluation of clinical outcomes with expression of molecular markers specified and others. Sufficient amount of biliary washings and tumor biopsies needed for analysis.
Measured: Once in the screening period (within 14 days of starting treatment)
Correlation of Treatment With Changes in Phenotypic Expression of Molecular Markers
Phenotypic expression of molecular markers before and after study treatment
Measured: Duration of study treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Jun 2004 (estimated)
- Study startJan 2004
- Primary completionAug 2008
- Study completionApr 2010
Why it stopped: The trial was discontinued early due to no confirmed partial responses.
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.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Adenocarcinoma of the Extrahepatic Bile DuctStudies of the same condition, open and under way.
- More trials run by National Cancer Institute (NCI)The 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Steven Cohen, Principal investigator, Fox Chase Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00085410
- Sponsor's protocol ID
- NCI-2009-00046
- Other IDs
- NCI-2009-00046, CDR0000369715, 03-042, 03-042, 6135
- Status last verified
- Jun 2017
- First submitted
- 10 Jun 2004
- Last updated
- 2 Jul 2017
- Results posted
- Yes, on ClinicalTrials.gov
Publications
Denlinger CS, Meropol NJ, Li T, Lewis NL, Engstrom PF, Weiner LM, Cheng JD, Alpaugh RK, Cooper H, Wright JJ, Cohen SJ. A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers. Clin Colorectal Cancer. 2014 Jun;13(2):81-6. doi: 10.1016/j.clcc.2013.12.005. Epub 2014 Jan 4.
PubMed 24512954
Study at a glance
From the registry record, last updated by the sponsor on 2 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II and Pharmacodynamic Study of PS-341 in Patients With Unresectable or Metastatic Adenocarcinoma of the Bile Duct or Gallbladder
- ClinicalTrials.gov ID
- NCT00085410
- Acronym / sponsor ID
- NCI-2009-00046
- Conditions
- Adenocarcinoma of the Extrahepatic Bile Duct, Adenocarcinoma of the Gallbladder, Advanced Adult Primary Liver Cancer, Gastrointestinal Cancer, Localized Unresectable Adult Primary Liver Cancer, Recurrent Adult Primary Liver Cancer
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: The trial was discontinued early due to no confirmed partial responses.
- Enrolment
- 20 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jan 2004
- Primary completion
- Aug 2008 (actual)
- Study completion
- Apr 2010 (actual)
- First posted
- 11 Jun 2004 (estimated)
- Results
- Posted 14 Jun 2017
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This phase II trial is studying how well bortezomib works as first-line systemic therapy in treating patients with unresectable locally advanced or metastatic adenocarcinoma (cancer) of the bile duct or gallbladder. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth.
Detailed description
PRIMARY OBJECTIVES:
- Determine the objective response rate in patients with unresectable locally advanced or metastatic adenocarcinoma of the bile duct or gallbladder treated with bortezomib.
SECONDARY OBJECTIVES:
- Determine the time to disease progression in patients treated with this drug.
II. Determine the overall survival of patients treated with this drug. III. Correlate the degree of proteasome inhibition in peripheral blood with degree of proteasome inhibition in tumor specimens of patients treated with this drug.
IV. Correlate phenotypic expression of NF-kB, p53, and other molecular markers in biliary washings and tumor biopsies with clinical outcomes in patients treated with this drug.
- Correlate treatment with this drug with changes in phenotypic expression of molecular markers in these patients.
OUTLINE: This is an open-label, multicenter study.
Patients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.
Patients are followed every 3 months for 1 year.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Arm I | Experimental | Drug: bortezomibPatients receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (34 listed)
- Absolute neutrophil count >= 1,500/mm3
- No psychiatric illness or social situation that would preclude study compliance
- Chemotherapy administered solely as a radiosensitizer or as adjuvant therapy and investigational or targeted therapies (i.e., inhibitors of the epidermal growth factor receptor) will not count toward the maximum of 2 prior regimens allowed
- Histologically or cytologically confirmed adenocarcinoma of the intrahepatic or extrahepatic bile duct or gallbladder:
- At least 1 unidimensionally measurable lesion >=20 mm by conventional techniques OR >= 10 mm by spiral CT scan
Key exclusion criteria (0 listed)
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 |
|---|---|---|
| bortezomibGiven IV | Drug | Arm I |
Primary outcome
Objective Response Rate
Time frame: Up to 1 year
Objective Response Rate (ORR) was determined by best response on radiologic assessment (computed tomography or magnetic resonance imaging) according to Response Evaluation Criteria in Solid Tumors (RECIST) 1.0.
5 secondary outcomes
Time to Disease Progression
Time frame: Up to 1 year
Overall Survival
Time frame: Up to 1 year
Correlation of the Degree of Proteasome Inhibition in Peripheral Blood With the Degree of Proteasome Inhibition in Tumor Specimens
Time frame: Once in the screening period (within 14 days of starting treatment)
Correlation of Phenotypic Expression of NF-kB, p53, and Other Molecular Markers in Biliary Washings and Tumor Biopsies With Clinical Outcomes
Time frame: Once in the screening period (within 14 days of starting treatment)
Correlation of Treatment With Changes in Phenotypic Expression of Molecular Markers
Time frame: Duration of study treatment
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Jul 2017.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 24512954Denlinger CS, Meropol NJ, Li T, Lewis NL, Engstrom PF, Weiner LM, Cheng JD, Alpaugh RK, Cooper H, Wright JJ, Cohen SJ. A phase II trial of the proteasome inhibitor bortezomib in patients with advanced biliary tract cancers. Clin Colorectal Cancer. 2014 Jun;13(2):81-6. doi: 10.1016/j.clcc.2013.12.005. Epub 2014 Jan 4.
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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.
Steven Cohen principal investigator
Fox Chase 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 2 study testing bortezomib in people with Adenocarcinoma of the Extrahepatic Bile Duct and Adenocarcinoma of the Gallbladder, run by National Cancer Institute (NCI) 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 34 inclusion and 0 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: stopped early, as of the sponsor's last update on 2 Jul 2017. 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 14 Jun 2017). 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?
Objective Response Rate (time frame: Up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00085410, which also lists 1 linked publication.
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 2 Jul 2017.