Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00030368
Bortezomib and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors
A Phase 1 study testing bortezomib, paclitaxel and laboratory biomarker analysis in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Phase I trial to study the effectiveness of combining bortezomib with paclitaxel in treating patients who have advanced or metastatic solid tumors. Bortezomib may stop the growth of cancer 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
- Unspecified Adult Solid Tumor, Protocol Specific
- What is being tested?
- bortezomib, paclitaxel and laboratory biomarker analysis
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2001to Feb 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
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor for which there is no curative treatment
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- WBC at least 3,000/mm^3
- Absolute neutrophil count at least 1,500/mm^3
Show all 34Show fewer
- Platelet count at least 100,000/mm^3
- Bilirubin normal
- AST/ALT no greater than 2.5 times upper limit of normal (ULN)
- Creatinine no greater than ULN
- Left ventricular function at least lower limit of normal if received prior doxorubicin
- No grade II or IV tilt-table test
- No symptomatic congestive heart failure
- No unstable angina pectoris
- No cardiac arrhythmia
- No thrombotic event within the past 6 months
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception
- No prior allergic reaction to compounds of similar chemical or biological composition to study drugs
- No other concurrent uncontrolled illness
- No ongoing or active infection
- No psychiatric illness or social situation that would preclude study compliance
- At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
- Prior paclitaxel allowed
- At least 2 weeks since prior hormonal therapy
- No concurrent steroids or hormonal therapy except steroids to prevent hypersensitivity reactions to paclitaxel or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes)
- At least 4 weeks since prior radiotherapy
- At least 4 weeks since prior surgery
- Recovered from prior therapy
- No other concurrent investigational agents
- No concurrent combination anti-retroviral therapy for HIV-positive patients
- No concurrent anticoagulation therapy
- Concurrent pamidronate or zoledronate allowed for treatment of hypercalcemia or for palliation of skeletal metastases
Who cannot join
None listed.
Trial locations and contacts
1 site in 1 country.
United States1 site
Ohio State University Medical Center
Columbus, Ohio, 43210
About this study
Official title: A Phase I Study of PS-341 in Combination With Paclitaxel in Metastatic Solid Tumors
Phase I trial to study the effectiveness of combining bortezomib with paclitaxel in treating patients who have advanced or metastatic solid tumors. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with paclitaxel may kill more tumor cells.
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of bortezomib when given in combination with paclitaxel in patients with locally advanced or metastatic solid tumors.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib 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 or greater than 80% 20S proteasome inhibition. Once the MTD is determined, an additional 6-9 patients are accrued and treated at that dose.
Patients are followed at 21 days.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
- Being tested
- bortezomib, paclitaxel, 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
paclitaxelDrug
Also called Anzatax, Asotax, TAX, Taxol
Given IV
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (bortezomib, paclitaxel) | Experimental | Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: bortezomib; Drug: paclitaxel; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose-limiting toxicity (DLT) defined as Common Terminology Criteria (CTC) version 2.0 grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity with the exception of asymptomatic neutropenia [ANC < 500]
Measured: 21 days
Maximum-tolerated dose (MTD) based on the incidence of DLT
Measured: 21 days
Dose of PS-341 that results in not more than 70% to 80% 20S proteasome inhibition [20S-PI] in combination with a paclitaxel
Measured: At baseline and at 1 hour of weeks 1, 2 and 4
Secondary outcomes (5)
Response according to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Reported descriptively using all eligible patients and evaluable patients separately. Response rates will include 95% confidence limits.
Measured: Up to 21 days
Change in the level of p27 and Bax proteins in peripheral blood mononuclear cells
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
Measured: From baseline to 6 hours of day 1 (week 1) and day 2 (week 2)
Change in plasma levels of TNF, IL-1, IL-6, and C-reactive protein
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
Measured: From baseline to 6 hours of day 2 (weeks 1 and 2)
Change in NF-kb biomarkers TRAP I and c-IAP-2 in tumor tissue blocks
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
Measured: From baseline to 6 hours of day 2 (weeks 1 and 2)
Change in phosphorylation of c-Jun and JNK in tumor tissue blocks
Descriptive data will be computed and compared using analysis of variance and non-parametric rank equivalents for continuous data and chi-square or Fisher's exact test for discrete data.
Measured: From baseline to 6 hours of day 2 (weeks 1 and 2)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Apr 2003 (estimated)
- Study startNov 2001
- Primary completionFeb 2009
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
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- Charles Shapiro, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00030368
- Sponsor's protocol ID
- NCI-2012-01408
- Other IDs
- 0158, NCI-1857, CDR0000069159, OSU-01H0147, U01CA076576
- Status last verified
- Jun 2013
- First submitted
- 14 Feb 2002
- Last updated
- 4 Jun 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 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 Paclitaxel in Metastatic Solid Tumors
- ClinicalTrials.gov ID
- NCT00030368
- Acronym / sponsor ID
- NCI-2012-01408
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Nov 2001
- Primary completion
- Feb 2009 (actual)
- First posted
- 9 Apr 2003 (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.
Phase I trial to study the effectiveness of combining bortezomib with paclitaxel in treating patients who have advanced or metastatic solid tumors. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with paclitaxel may kill more tumor cells.
Detailed description
PRIMARY OBJECTIVES:
- Determine the maximum tolerated dose of bortezomib when given in combination with paclitaxel in patients with locally advanced or metastatic solid tumors.
OUTLINE: This is a multicenter, dose-escalation study of bortezomib.
Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bortezomib 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 or greater than 80% 20S proteasome inhibition. Once the MTD is determined, an additional 6-9 patients are accrued and treated at that dose.
Patients are followed at 21 days.
PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.
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, paclitaxel) | Experimental | Drug: bortezomib, Drug: paclitaxel, Other: laboratory biomarker analysisPatients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat 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 (34 listed)
- Histologically or cytologically confirmed locally advanced or metastatic solid tumor for which there is no curative treatment
- No known brain metastases
- Performance status - ECOG 0-2
- Performance status - Karnofsky 60-100%
- WBC at least 3,000/mm^3
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 |
|---|---|---|
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Treatment (bortezomib, paclitaxel) |
| paclitaxelAlso: Anzatax, Asotax, TAX, TaxolGiven IV | Drug | Treatment (bortezomib, paclitaxel) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (bortezomib, paclitaxel) |
Primary outcome
Dose-limiting toxicity (DLT) defined as Common Terminology Criteria (CTC) version 2.0 grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity with the exception of asymptomatic neutropenia [ANC < 500]
Time frame: 21 days
Maximum-tolerated dose (MTD) based on the incidence of DLT
Time frame: 21 days
Dose of PS-341 that results in not more than 70% to 80% 20S proteasome inhibition [20S-PI] in combination with a paclitaxel
Time frame: At baseline and at 1 hour of weeks 1, 2 and 4
5 secondary outcomes
Response according to the Response Evaluation Criteria in Solid Tumors (RECIST) Committee
Time frame: Up to 21 days
Change in the level of p27 and Bax proteins in peripheral blood mononuclear cells
Time frame: From baseline to 6 hours of day 1 (week 1) and day 2 (week 2)
Change in plasma levels of TNF, IL-1, IL-6, and C-reactive protein
Time frame: From baseline to 6 hours of day 2 (weeks 1 and 2)
Change in NF-kb biomarkers TRAP I and c-IAP-2 in tumor tissue blocks
Time frame: From baseline to 6 hours of day 2 (weeks 1 and 2)
Change in phosphorylation of c-Jun and JNK in tumor tissue blocks
Time frame: From baseline to 6 hours of day 2 (weeks 1 and 2)
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 4 Jun 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.
Charles Shapiro principal investigator
Ohio State University
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, paclitaxel and laboratory biomarker analysis 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 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: finished, as of the sponsor's last update on 4 Jun 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?
Dose-limiting toxicity (DLT) defined as Common Terminology Criteria (CTC) version 2.0 grade 3 or greater non-hematologic toxicity or grade 4 hematologic toxicity with the exception of asymptomatic neutropenia [ANC < 500] (time frame: 21 days). The study lists 3 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 4 Jun 2013.