Tanespimycin and Bortezomib in Treating Patients With Advanced Solid Tumors or Lymphomas
A Phase I Trial Of 17-Allylaminogeldanamycin (17-AAG) And PS341 In Advanced Malignancies
8 other identifiers
interventional
36
1 country
1
Brief Summary
This phase I trial is studying the side effects and best dose of giving tanespimycin together with bortezomib in treating patients with advanced solid tumors or lymphomas. (Accrual for lymphoma patients closed as of 11/27/09) Drugs used in chemotherapy, such as tanespimycin, work in different ways to stop cancer cells from dividing so they stop growing or die. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. It may also increase the effectiveness of tanespimycin by making cancer cells more sensitive to the drug. Combining tanespimycin with bortezomib may kill more cancer cells.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 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
November 1, 2004
CompletedFirst Submitted
Initial submission to the registry
November 9, 2004
CompletedFirst Posted
Study publicly available on registry
November 9, 2004
CompletedPrimary Completion
Last participant's last visit for primary outcome
March 1, 2010
CompletedFebruary 24, 2014
October 1, 2011
5.3 years
November 9, 2004
February 21, 2014
Conditions
Outcome Measures
Primary Outcomes (7)
MTD of tanespimycin in combination with bortezomib in the treatment of solid tumors
Defined as the dose level below the lowest dose that induces dose-limiting toxicity in at least one-third of the solid tumor patients (at least 2 of a maximum of 6 new patients).
At 3 weeks
Toxicity of tanespimycin in combination with bortezomib in the treatment of solid tumors
Defined by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) version 3.0 as adverse events that are classified as either possibly, probably, or definitely related to study treatment. Non-hematologic toxicities will be evaluated via the ordinal common toxicity criteria (CTC) standard toxicity grading. Hematologic toxicity measures of thrombocytopenia, neutropenia, and leukopenia will be assessed using continuous variables as the outcome measures (primarily nadir) as well as categorization via CTC standard toxicity grading.
At 3 weeks
Changes in biomarkers in peripheral blood mononuclear cells and tumor specimens from patients with advanced solid tumors or lymphomas
Changes in the levels of expressions of HSP70, client proteins, and ubquitination of proteins in PBMC at the different dose levels as well as at the different time points will be descriptively summarized. The degree of proteasome inhibition will be quantitated whenever possible and the results will be displayed graphically and analyzed using simple descriptive statistics.
Baseline, days 4, 8, and 11 of course 1, and at the end of treatment study
Responses in patients treated with this regimen
Evaluated using the modified Response Evaluation Criteria In Solid Tumors (RECIST) criteria. Summarized by simple descriptive summary statistics delineating complete and partial responses as well as stable and progressive disease (overall and by tumor group).
Every 6 weeks
Time until hematologic nadirs (WBC, ANC, platelets)
Days 4, 8, and 11 of course 1 and then every 21 days
Time to progression
Every 6 weeks
Time to treatment failure
Defined as the time from registration to documentation of progression, unacceptable toxicity, or refusal to continue participation by the patient.
At 3 weeks and every 6 weeks
Study Arms (1)
Treatment (chemotherapy and enzyme inhibitor therapy)
EXPERIMENTALPatients receive tanespimycin IV over 1-2 hours and 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. Cohorts of 3-6 patients receive escalating doses of tanespimycin and bortezomib until the 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. Once the MTD is determined, at least 12 additional patients are treated as above\* at the MTD. NOTE: \*Bortezomib is not administered on day 1 of course 1 only. Patients are followed at 3 months.
Interventions
Given IV
Correlative studies
Eligibility Criteria
You may qualify if:
- Histologically confirmed solid tumor or lymphomas (Accrual for Lymphoma Patients Closed as of 11/27/09)
- Refractory to standard treatment OR no standard treatment that is potentially curative or capable of prolonging life expectancy exists
- Tumor amenable to biopsy (patients accrued at the MTD only)
- No CNS metastases
- Performance status - ECOG 0-2
- At least 12 weeks
- Absolute neutrophil count ≥ 1,500/mm\^3
- Platelet count ≥ 100,000/mm\^3
- Hemoglobin ≥ 9.0 g/dL
- Bilirubin ≤ 2 times upper limit of normal (ULN)
- AST ≤ 2.5 times ULN
- Alkaline phosphatase ≤ 2 times ULN (5 times ULN if due to liver involvement)
- Creatinine ≤ 2 times ULN
- QTc \< 500 msec for men (470 msec for women)
- LVEF \> 40% by echocardiogram
- +48 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
Mayo Clinic
Rochester, Minnesota, 55905, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Charles Erlichman
Mayo Clinic
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
November 9, 2004
First Posted
November 9, 2004
Study Start
November 1, 2004
Primary Completion
March 1, 2010
Last Updated
February 24, 2014
Record last verified: 2011-10