PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma
A Phase I Study of PXD101 in Combination With 17-AAG in Advanced Malignancies
5 other identifiers
interventional
36
1 country
1
Brief Summary
This phase I trial is studying the side effects and best dose of giving PDX101 together with 17-AAG in treating patients with metastatic or unresectable solid tumors or lymphoma. PDX101 may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the cancer. Drugs used in chemotherapy, such as 17-N-allylamino-17-demethoxygeldanamycin (17-AAG), work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Giving PXD101 together with 17-AAG 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
May 1, 2006
CompletedFirst Submitted
Initial submission to the registry
July 19, 2006
CompletedFirst Posted
Study publicly available on registry
July 20, 2006
CompletedPrimary Completion
Last participant's last visit for primary outcome
February 1, 2008
CompletedMay 16, 2013
May 1, 2013
1.8 years
July 19, 2006
May 15, 2013
Conditions
Outcome Measures
Primary Outcomes (2)
Maximum tolerated dose (MTD), based on the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) v3.0
Up to 21 days
Number and severity of toxicity incidents, based on the NCI CTCAE v3.0
Dose-toxicity relationship may be explored by performing exact logistic regression analysis.
Up to 2 years
Secondary Outcomes (7)
Cmax (observed maximum plasma concentration)
Day 4
Tmax (time to Cmax)
Day 4
AUC0-lqc (the area under the plasma concentration-time curve as determined by the linear trapezoidal rule and where lqc is last quantifiable concentration)
Day 4
AUC0-omega (the area under the plasma concentration-time curve from time 0 to infinity as determined by AUC0-lqc + lqc/-omega)
Day 4
T1/2 (the terminal disposition half-life calculated as ln(2)/-beta)
Day 4
- +2 more secondary outcomes
Study Arms (1)
Treatment (tanespimycin, belinostat)
EXPERIMENTALPatients receive 17-AAG IV over 2 hours on days 1, 4, 8, and 11 and PXD101 IV over 30 minutes on days 1-5. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. Cohorts of 3-6 patients receive escalating doses of 17-AAG and PDX101 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. Up to 12 patients are treated at the MTD. Patients undergo blood collection on days 1 and 4 of course 1 for pharmacokinetic studies.
Interventions
Correlative studies
Eligibility Criteria
You may qualify if:
- Patients must have histologically confirmed malignancy (solid tumor or lymphoma) that is metastatic or unresectable and for which standard curative or palliative measures do not exist or are no longer effective
- Patients may have received prior treatment with either any HDAC inhibitor therapy or 17AAG, as long as they did not experience dose limiting toxicity (DLT) with these prior treatments; DLTs include
- Toxicity: neutrophils; DLT: grade 4 toxicity (\< 500/μL) for \>= 7 days
- Toxicity: febrile neutropenia; DLT: ANC \< 1000/μL of any duration accompanied by fever \>= 38.5ºC
- Toxicity: platelets; DLT: grade 4 toxicity (\< 25,000/μL) for \>= 7 days or of any duration if accompanied by clinically significant bleeding
- Toxicity: non-hematologic; DLT: \>= grade 3 as per NCI Common Terminology Criteria for Adverse Events, Version 3.0\*\* (except alopecia); \*\* for nausea and vomiting, grade 3 toxicity with maximal anti-emetic treatment will be considered dose-limiting; grade 3 diarrhea in spite of maximal anti-diarrheal therapy will be considered dose-limiting; hypersensitivity reactions to 17AAG will not be considered a DLT; asymptomatic grade 3 hypophosphatemia will not be considered a DLT
- Toxicity: cardiac; DLT: ≥ grade 3 QTc prolongation
- ECOG performance status =\< 2 (Karnofsky \>= 60%)
- Life expectancy of greater than 12 weeks
- Leukocytes \>= 3,000/mcL
- Absolute neutrophil count \>= 1,500/mcL
- Platelets \>= 75,000/mcL
- Total bilirubin within normal institutional limits
- AST(SGOT)/ALT(SGPT) =\< 2.5 X institutional upper limit of normal
- Creatinine within normal institutional limits OR creatinine clearance \>= 60 mL/min/1.73 m\^2 for patients with creatinine levels above institutional normal
- +4 more criteria
You may not qualify if:
- Patients who have had chemotherapy or radiotherapy within 4 weeks (6 weeks for nitrosoureas or mitomycin C) prior to entering the study or those who have not recovered (≤ grade 1) from clinically significant adverse events due to agents administered more than 4 weeks earlier
- Patients may not be receiving any 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 adverse events
- History of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101; there are no known allergic reactions attributed to compounds of similar chemical or biological composition to 17AAG; patients with known egg allergy should be excluded as the agent is diluted in EPL diluent
- Patients should not have taken valproic acid, another histone deacetylase inhibitor, for at least 2 weeks prior to enrollment
- Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, or psychiatric illness/social situations that would limit compliance with study requirements
- Pregnant women are excluded from this study because PXD101 is an HDAC inhibitor 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 PXD101, breastfeeding should be discontinued if the mother is treated with PXD101; these potential risks may also apply to other agents used in this study
- HIV-positive patients on combination antiretroviral therapy are ineligible because of the potential for pharmacokinetic interactions with PXD101; in addition, these patients are at increased risk of lethal infections when treated with marrow-suppressive therapy; appropriate studies will be undertaken in patients receiving combination antiretroviral therapy when indicated
- History of allergic reactions to eggs
- Patients who have significant cardiac disease including heart failure that meets New York Heart Association (NYHA) class III and IV definitions, history of myocardial infarction within 12 months of study entry, ischemic or severs valvular heart disease, uncontrolled dysrhythmias, uncontrolled hypertension, a condition requiring anti-arrhythmic therapy, or poorly controlled or unstable angina pectoris
- Patients who have a history of serious ventricular arrhythmia (VT or VF, \>= 3 beats in a row) or QTc \>= 450 msec for men and 470 msec for women or a history of long QT Syndrome
- Patients taking concomitant medications that prolong or may prolong QTc or may cause Tosade des Pointes
Contact the study team to confirm eligibility.
Sponsors & Collaborators
Study Sites (1)
University of Wisconsin Hospital and Clinics
Madison, Wisconsin, 53792, United States
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
George Wilding
University of Wisconsin, Madison
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
July 19, 2006
First Posted
July 20, 2006
Study Start
May 1, 2006
Primary Completion
February 1, 2008
Last Updated
May 16, 2013
Record last verified: 2013-05