Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00007878
Bortezomib, Fluorouracil, and Leucovorin Calcium in Treating Patients With Solid Tumors That Are Metastatic or Cannot Be Removed By Surgery
A Phase 1 study testing bortezomib, fluorouracil and leucovorin calcium in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
This phase I trial studies the side effects and best dose of bortezomib when given together with fluorouracil and leucovorin calcium in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- bortezomib, fluorouracil and leucovorin calcium
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2000to Jan 2008
- 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 cytological confirmed malignancy which is metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- All patients will have advanced malignancy confirmed by review of their biopsy specimens by the Division of Pathology of the City of Hope National Medical Center, the University of Southern California/LA County/Norris Comprehensive Cancer Center, or the University of California at Davis
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) and an estimated survival of at least 3 months
- Absolute neutrophil count >= 1,500/ul
- Platelets >= 100,000/ul
- Total bilirubin =< within the institutional normal
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- Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =< 2.5 x the upper limits of institutional normal
- Serum creatinine =< 1.5 mg/dl
- Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) prior to study entry and for the duration of study participation; should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
- Ability to understand and the willingness to sign a written informed consent document
Who cannot join
- Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study and 6 weeks from nitrosourea-containing chemotherapy; all patients should have recovered from all toxicities of prior chemo and radiation therapy
- Patients undergoing therapy with other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- Pregnant and nursing women are excluded from this study because PS-341 is an investigational agent, and the anti-proliferative activity of PS-341 may be harmful to the developing fetus or nursing infant
- Human immunodeficiency virus HIV-positive patients receiving anti-retroviral therapy (HAART) are excluded from the study because of possible pharmacokinetic interactions
- Patients with electrocardiogram (EKG) evidence of acute ischemia or significant conduction abnormality (bifascicular block, defined as left anterior hemiblock in the presence of right bundle branch block, 2nd or 3rd degrees atrioventricular [AV] blocks); any history of cardiac or cerebrovascular disease due to hypotension and tachycardia
- Patients who had any major surgery within 2 weeks
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Southern California
Los Angeles, California, 90033-0804
About this study
Official title: A Phase I Study of PS-341 in Combination With 5-FU/LV in Solid Tumors
This phase I trial studies the side effects and best dose of bortezomib when given together with fluorouracil and leucovorin calcium in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with chemotherapy may be an effective treatment for solid tumors.
Read the detailed description
PRIMARY OBJECTIVES:
- To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of PS-341 (bortezomib) when administered as a bolus injection two times a week (on days 1 and 4) for 2 weeks followed by one week of rest.
II. To evaluate the pharmacodynamics of PS-341 by determining the 20S proteasome and nuclear factor kappa-light chain enhancer of activated B cells (NFkB) inhibition in blood of patients treated with intravenous PS-341 combined with weekly fluorouracil (5-FU) and leucovorin calcium (LV).
SECONDARY OBJECTIVES:
- To identify any objective tumor response in patients treated with intravenous PS-341.
II. To evaluate the relationship between inhibition of the 20S proteasome and NFkB and clinical toxicity.
III. To obtain preliminary data on molecular correlates of response to PS-341 and 5-FU and LV including genes involved in apoptosis, cell cycle control, transcriptional regulation and adhesion/angiogenesis based on the mechanisms of PS-341 IV. To examine the pharmacokinetics of 5-FU when co-administered with PS-341.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive bortezomib intravenously (IV) on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
- Being tested
- bortezomib, fluorouracil, leucovorin calcium, pharmacological study, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
fluorouracilDrug
Also called 5-fluorouracil, 5-Fluracil, 5-FU
Given IV
Also called CF, CFR, LV
Given IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bortezomib, fluorouracil, leucovorin calcium) | Experimental | Patients receive bortezomib IV on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: bortezomib; Drug: fluorouracil; Drug: leucovorin calcium; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
MTD, defined as the highest dose tested in which none or only one patient experienced DLT attributable to the study drug(s), when at least 6 patients were treated at that dose and are evaluable for toxicity, graded according to the NCI CTC version 2.0
Measured: Up to 21 days
Incidence of adverse events, graded according to NCI CTC version 2.0
The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.
Measured: Up to 7 years
Secondary outcomes (2)
Survival
Will be summarized with Kaplan-Meier plots.
Measured: Up to 7 years
Time to failure
Will be summarized with Kaplan-Meier plots.
Measured: Up to 7 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Feb 2004 (estimated)
- Study startSep 2000
- Primary completionJan 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Unspecified Adult Solid Tumor, Protocol SpecificStudies 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 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Heinz-Josef Lenz, Principal investigator, University of Southern California
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00007878
- Sponsor's protocol ID
- NCI-2012-03190
- Other IDs
- NCI-2012-03190, NCI-T99-0048, LAC-USC-0C003, CHNMC-PHI-27, CDR0000068327, PHI-27 (USC 0C-00-03), T99-0048, U01CA062505
- Status last verified
- Dec 2013
- First submitted
- 6 Jan 2001
- Last updated
- 11 Dec 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 11 Dec 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase I Study of PS-341 in Combination With 5-FU/LV in Solid Tumors
- ClinicalTrials.gov ID
- NCT00007878
- Acronym / sponsor ID
- NCI-2012-03190
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 30 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Sep 2000
- Primary completion
- Jan 2008 (actual)
- First posted
- 16 Feb 2004 (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.
This phase I trial studies the side effects and best dose of bortezomib when given together with fluorouracil and leucovorin calcium in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with chemotherapy may be an effective treatment for solid tumors.
Detailed description
PRIMARY OBJECTIVES:
- To determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of PS-341 (bortezomib) when administered as a bolus injection two times a week (on days 1 and 4) for 2 weeks followed by one week of rest.
II. To evaluate the pharmacodynamics of PS-341 by determining the 20S proteasome and nuclear factor kappa-light chain enhancer of activated B cells (NFkB) inhibition in blood of patients treated with intravenous PS-341 combined with weekly fluorouracil (5-FU) and leucovorin calcium (LV).
SECONDARY OBJECTIVES:
- To identify any objective tumor response in patients treated with intravenous PS-341.
II. To evaluate the relationship between inhibition of the 20S proteasome and NFkB and clinical toxicity.
III. To obtain preliminary data on molecular correlates of response to PS-341 and 5-FU and LV including genes involved in apoptosis, cell cycle control, transcriptional regulation and adhesion/angiogenesis based on the mechanisms of PS-341 IV. To examine the pharmacokinetics of 5-FU when co-administered with PS-341.
OUTLINE: This is a dose-escalation study of bortezomib.
Patients receive bortezomib intravenously (IV) on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Treatment (bortezomib, fluorouracil, leucovorin calcium) | Experimental | Drug: bortezomib, Drug: fluorouracil, Drug: leucovorin calcium, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive bortezomib IV on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- Patients must have histologically or cytological confirmed malignancy which is metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
- All patients will have advanced malignancy confirmed by review of their biopsy specimens by the Division of Pathology of the City of Hope National Medical Center, the University of Southern California/LA County/Norris Comprehensive Cancer Center, or the University of California at Davis
- Eastern Cooperative Oncology Group (ECOG) performance status =< 2 (Karnofsky >= 60%) and an estimated survival of at least 3 months
- Absolute neutrophil count >= 1,500/ul
- Platelets >= 100,000/ul
Key exclusion criteria (8 listed)
- Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study and 6 weeks from nitrosourea-containing chemotherapy; all patients should have recovered from all toxicities of prior chemo and radiation therapy
- Patients undergoing therapy with other investigational agents
- Patients with known brain metastases should be excluded from this clinical trial because of their poor prognosis and because they often develop progressive neurologic dysfunction that would confound the evaluation of neurologic and other toxicities
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
- Pregnant and nursing women are excluded from this study because PS-341 is an investigational agent, and the anti-proliferative activity of PS-341 may be harmful to the developing fetus or nursing infant
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 |
|---|---|---|
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Treatment (bortezomib, fluorouracil, leucovorin calcium) |
| fluorouracilAlso: 5-fluorouracil, 5-Fluracil, 5-FUGiven IV | Drug | Treatment (bortezomib, fluorouracil, leucovorin calcium) |
| leucovorin calciumAlso: CF, CFR, LVGiven IV | Drug | Treatment (bortezomib, fluorouracil, leucovorin calcium) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (bortezomib, fluorouracil, leucovorin calcium) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (bortezomib, fluorouracil, leucovorin calcium) |
Primary outcome
MTD, defined as the highest dose tested in which none or only one patient experienced DLT attributable to the study drug(s), when at least 6 patients were treated at that dose and are evaluable for toxicity, graded according to the NCI CTC version 2.0
Time frame: Up to 21 days
Incidence of adverse events, graded according to NCI CTC version 2.0
Time frame: Up to 7 years
The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.
2 secondary outcomes
Survival
Time frame: Up to 7 years
Time to failure
Time frame: Up to 7 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 11 Dec 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.
Heinz-Josef Lenz principal investigator
University of Southern California
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 bortezomib, fluorouracil and leucovorin calcium in people with Unspecified Adult Solid Tumor, Protocol Specific, 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 10 inclusion and 8 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 11 Dec 2013. 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?
MTD, defined as the highest dose tested in which none or only one patient experienced DLT attributable to the study drug(s), when at least 6 patients were treated at that dose and are evaluable for toxicity, graded according to the NCI CTC version 2.0 (time frame: Up to 21 days). 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 11 Dec 2013.