A Dose Finding Phase I Trial of the Combination of Topotecan and PS-341, a Novel Proteasome Inhibitor, in Advanced Malignancies
4 other identifiers
interventional
25
1 country
1
Brief 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. 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
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P25-P50 for phase_1
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
July 1, 2003
CompletedFirst Submitted
Initial submission to the registry
September 10, 2003
CompletedFirst Posted
Study publicly available on registry
September 11, 2003
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2006
CompletedFebruary 1, 2013
January 1, 2013
2.6 years
September 10, 2003
January 31, 2013
Conditions
Outcome Measures
Primary Outcomes (2)
Dose limiting toxicities
Up to 3 years
Maximum tolerated dose (MTD)
21 days
Secondary Outcomes (4)
Pharmacokinetics of topotecan hydrochloride
5 minutes immediately after sample collection
Levels of topoisomerase I
Up to 3 years
DNA repair enzymes
Up to 3 years
Objective response according to the RECIST criteria
Up to 3 years
Study Arms (1)
Treatment (topotecan hydrochloride, bortezomib)
EXPERIMENTALPatients 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.
Interventions
Given IV
Given IV
Correlative studies
Correlative studies
Eligibility Criteria
You may qualify if:
- 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
- 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
You may not qualify if:
- 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
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Yale University
New Haven, Connecticut, 06520-8032, United States
MeSH Terms
Interventions
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
John Murren
Yale University
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- NIH
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
September 10, 2003
First Posted
September 11, 2003
Study Start
July 1, 2003
Primary Completion
February 1, 2006
Last Updated
February 1, 2013
Record last verified: 2013-01