Unspecified Adult Solid Tumor, Protocol SpecificPhase 1NCT00068484
A Dose Finding Phase I Trial of the Combination of Topotecan and PS-341, a Novel Proteasome Inhibitor, in Advanced Malignancies
A Phase 1 study testing topotecan hydrochloride, bortezomib and pharmacological study in people with Unspecified Adult Solid Tumor, Protocol Specific, run by National Cancer Institute (NCI) at 1 site in United States.
Trial summary
Drugs used in chemotherapy such as topotecan use different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining topotecan with bortezomib may kill more tumor cells. 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?
- topotecan hydrochloride, bortezomib and pharmacological study
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteUnited States
- Study dates
- Jul 2003to Feb 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 must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Tumor accessible to core needle biopsy and willingness to undergo this procedure prior to the start of treatment
- Evaluable disease as defined in the RECIST criteria
- ECOG performance status =< 2
- Life expectancy of greater than 3 months
- Absolute neutrophil count > 1,500/ul
Show all 14Show fewer
- Platelets > 100,000/ul
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) =< 2.5 X institutional upper limit of normal
- Creatinine < 2.0 mg/ml
- Ability to understand and the willingness to sign a written informed consent document
- Metastatic brain or meningeal tumors are allowed if the patient is > 1 month from surgery and/or radiation and is clinically stable with respect to the tumor at the time of the study entry and currently off corticosteroids
- Pregnancy test for pre-menopausal women
- The effects of PS-341 and topotecan on the developing human fetus are unknown; for this reason women of childbearing 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
Who cannot join
- Creatinine clearance < 40 mL/min
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, PS-341 or other agents used in this study
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because topotecan is an agent with the potential for teratogenic or abortifacient effects; because there is an unknown but potential risk for adverse events in nursing infants secondary to treatment of the mother with topotecan and PS-341, breastfeeding should be discontinued; these potential risks may also apply to other agents used in this study
- Because patients with immune deficiency are at increased risk of lethal infections when treated with marrow-suppressive therapy, HIV-positive patients receiving combination anti-retroviral therapy are excluded from the study because of possible pharmacokinetic interactions with topotecan and PS-341 or other agents administered during the study.; appropriate studies will be undertaken for patients receiving combination anti-retroviral therapy when indicated
Trial locations and contacts
1 site in 1 country.
About this study
Drugs used in chemotherapy such as topotecan use different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining topotecan with bortezomib may kill more tumor cells. This phase I trial is studying the side effects and best dose of topotecan and bortezomib when given together in treating patients with metastatic or unresectable cancer
Read the detailed description
PRIMARY OBJECTIVES:
- Determine the safety of the combination of PS-341 and topotecan. II. Determine the dose limiting toxicities and maximum tolerated dose as well as the recommended phase II doses of the combination.
III. Assess the pharmacokinetics of topotecan alone and in combination with PS-341.
SECONDARY OBJECTIVES:
- Estimate the objective response rate of a combination of PS-341 and topotecan delivered on days 1-5 every three weeks as defined by the RECIST criteria.
II. Assess the pharmacodynamics of topo I levels. III. Determine the expression of the DNA repair enzyme XRCC1 in tumor biopsies.
OUTLINE: This is a dose-escalation study.
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 20-25 patients will be accrued for this study.
- Being tested
- topotecan hydrochloride, bortezomib, pharmacological study, laboratory biomarker analysis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
topotecan hydrochlorideDrug
Also called hycamptamine, Hycamtin, SKF S-104864-A, TOPO
Given IV
bortezomibDrug
Also called LDP 341, MLN341, VELCADE
Given IV
Also called pharmacological studies
Correlative studies
laboratory biomarker analysisOther
Correlative studies
| Study group | Role | What they receive |
|---|---|---|
| Treatment (topotecan hydrochloride, bortezomib) | Experimental | Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity. Receives: Drug: topotecan hydrochloride; Drug: bortezomib; Other: pharmacological study; Other: laboratory biomarker analysis |
What is being measured
The primary outcome is the main question the study is designed to answer.
Dose limiting toxicities
Measured: Up to 3 years
Maximum tolerated dose (MTD)
Measured: 21 days
Secondary outcomes (4)
Pharmacokinetics of topotecan hydrochloride
Measured: 5 minutes immediately after sample collection
Levels of topoisomerase I
Measured: Up to 3 years
DNA repair enzymes
Measured: Up to 3 years
Objective response according to the RECIST criteria
Measured: Up to 3 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Sep 2003 (estimated)
- Study startJul 2003
- Primary completionFeb 2006
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
- 25 participants (actual)
Sponsor and investigators
- Lead sponsor
- National Cancer Institute (NCI)
- Sponsor type
- US National Institutes of Health
- Responsible party
- Sponsor
- Investigators
- John Murren, Principal investigator, Yale University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00068484
- Sponsor's protocol ID
- NCI-2013-00044
- Other IDs
- HIC #12760, R21CA097750, CDR0000322889
- Status last verified
- Jan 2013
- First submitted
- 10 Sep 2003
- Last updated
- 1 Feb 2013
- Results posted
- No
Study at a glance
From the registry record, last updated by the sponsor on 1 Feb 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Dose Finding Phase I Trial of the Combination of Topotecan and PS-341, a Novel Proteasome Inhibitor, in Advanced Malignancies
- ClinicalTrials.gov ID
- NCT00068484
- Acronym / sponsor ID
- NCI-2013-00044
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 25 participants (actual)
- Lead sponsor
- National Cancer Institute (NCI)US National Institutes of Health
- Study start
- Jul 2003
- Primary completion
- Feb 2006 (actual)
- First posted
- 11 Sep 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.
Drugs used in chemotherapy such as topotecan use different ways to stop tumor cells from dividing so they stop growing or die. Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for tumor cell growth. Combining topotecan with bortezomib may kill more tumor cells. This phase I trial is studying the side effects and best dose of topotecan and bortezomib when given together in treating patients with metastatic or unresectable cancer
Detailed description
PRIMARY OBJECTIVES:
- Determine the safety of the combination of PS-341 and topotecan. II. Determine the dose limiting toxicities and maximum tolerated dose as well as the recommended phase II doses of the combination.
III. Assess the pharmacokinetics of topotecan alone and in combination with PS-341.
SECONDARY OBJECTIVES:
- Estimate the objective response rate of a combination of PS-341 and topotecan delivered on days 1-5 every three weeks as defined by the RECIST criteria.
II. Assess the pharmacodynamics of topo I levels. III. Determine the expression of the DNA repair enzyme XRCC1 in tumor biopsies.
OUTLINE: This is a dose-escalation study.
Patients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of topotecan and bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose at which no more than 1 of 6 patients experience dose-limiting toxicity.
PROJECTED ACCRUAL: A total of 20-25 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 (topotecan hydrochloride, bortezomib) | Experimental | Drug: topotecan hydrochloride, Drug: bortezomib, Other: pharmacological study, Other: laboratory biomarker analysisPatients receive topotecan IV over 30 minutes on days 1-5. Beginning with course 2, patients also receive bortezomib IV over 3-5 seconds on days 1, 4, 8, and 11. 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 (14 listed)
- Patients must have histologically confirmed malignancy that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Tumor accessible to core needle biopsy and willingness to undergo this procedure prior to the start of treatment
- Evaluable disease as defined in the RECIST criteria
- ECOG performance status =< 2
- Life expectancy of greater than 3 months
Key exclusion criteria (8 listed)
- Creatinine clearance < 40 mL/min
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study
- Those who have not recovered from adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any other investigational agents
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to topotecan, PS-341 or other agents used in this study
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 |
|---|---|---|
| topotecan hydrochlorideAlso: hycamptamine, Hycamtin, SKF S-104864-A, TOPOGiven IV | Drug | Treatment (topotecan hydrochloride, bortezomib) |
| bortezomibAlso: LDP 341, MLN341, VELCADEGiven IV | Drug | Treatment (topotecan hydrochloride, bortezomib) |
| pharmacological studyAlso: pharmacological studiesCorrelative studies | Other | Treatment (topotecan hydrochloride, bortezomib) |
| laboratory biomarker analysisCorrelative studies | Other | Treatment (topotecan hydrochloride, bortezomib) |
Primary outcome
Dose limiting toxicities
Time frame: Up to 3 years
Maximum tolerated dose (MTD)
Time frame: 21 days
4 secondary outcomes
Pharmacokinetics of topotecan hydrochloride
Time frame: 5 minutes immediately after sample collection
Levels of topoisomerase I
Time frame: Up to 3 years
DNA repair enzymes
Time frame: Up to 3 years
Objective response according to the RECIST criteria
Time frame: Up to 3 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 1 Feb 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.
John Murren principal investigator
Yale 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 topotecan hydrochloride, bortezomib and pharmacological study 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 14 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 1 Feb 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 toxicities (time frame: Up to 3 years). 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 1 Feb 2013; AzTrials last refreshed its copy on 6 Nov 2026.