PXD101 and 17-N-Allylamino-17-Demethoxygeldanamycin in Treating Patients With Metastatic or Unresectable Solid Tumors or Lymphoma

Stopped early · Phase 1

Conditions studied: Adult Nasal Type Extranodal NK/T-cell Lymphoma, Anaplastic Large Cell Lymphoma, Angioimmunoblastic T-cell Lymphoma, Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue, Intraocular Lymphoma, Nodal Marginal Zone B-cell Lymphoma, Post-transplant Lymphoproliferative Disorder, Recurrent Adult Burkitt Lymphoma, Recurrent Adult Diffuse Large Cell Lymphoma, Recurrent Adult Diffuse Mixed Cell Lymphoma, Recurrent Adult Diffuse Small Cleaved Cell Lymphoma, Recurrent Adult Grade III Lymphomatoid Granulomatosis, Recurrent Adult Hodgkin Lymphoma, Recurrent Adult Immunoblastic Large Cell Lymphoma, Recurrent Adult Lymphoblastic Lymphoma, Recurrent Adult T-cell Leukemia/Lymphoma, Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma, Recurrent Grade 1 Follicular Lymphoma, Recurrent Grade 2 Follicular Lymphoma, Recurrent Grade 3 Follicular Lymphoma, Recurrent Mantle Cell Lymphoma, Recurrent Marginal Zone Lymphoma, Recurrent Mycosis Fungoides/Sezary Syndrome, Recurrent Small Lymphocytic Lymphoma, Small Intestine Lymphoma, Splenic Marginal Zone Lymphoma, Stage III Adult Burkitt Lymphoma, Stage III Adult Diffuse Large Cell Lymphoma, Stage III Adult Diffuse Mixed Cell Lymphoma, Stage III Adult Diffuse Small Cleaved Cell Lymphoma, Stage III Adult Hodgkin Lymphoma, Stage III Adult Immunoblastic Large Cell Lymphoma, Stage III Adult Lymphoblastic Lymphoma, Stage III Adult T-cell Leukemia/Lymphoma, Stage III Cutaneous T-cell Non-Hodgkin Lymphoma, Stage III Grade 1 Follicular Lymphoma, Stage III Grade 2 Follicular Lymphoma, Stage III Grade 3 Follicular Lymphoma, Stage III Mantle Cell Lymphoma, Stage III Marginal Zone Lymphoma, Stage III Mycosis Fungoides/Sezary Syndrome, Stage III Small Lymphocytic Lymphoma, Stage IV Adult Burkitt Lymphoma, Stage IV Adult Diffuse Large Cell Lymphoma, Stage IV Adult Diffuse Mixed Cell Lymphoma, Stage IV Adult Diffuse Small Cleaved Cell Lymphoma, Stage IV Adult Hodgkin Lymphoma, Stage IV Adult Immunoblastic Large Cell Lymphoma, Stage IV Adult Lymphoblastic Lymphoma, Stage IV Adult T-cell Leukemia/Lymphoma, Stage IV Cutaneous T-cell Non-Hodgkin Lymphoma, Stage IV Grade 1 Follicular Lymphoma, Stage IV Grade 2 Follicular Lymphoma, Stage IV Grade 3 Follicular Lymphoma, Stage IV Mantle Cell Lymphoma, Stage IV Marginal Zone Lymphoma, Stage IV Mycosis Fungoides/Sezary Syndrome, Stage IV Small Lymphocytic Lymphoma, Unspecified Adult Solid Tumor, Protocol Specific, Waldenström Macroglobulinemia

In brief

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.

Key facts

Study ID: NCT00354185
Run by: National Cancer Institute (NCI)
People needed: 36
Starts: 2006-05-01
Last updated by the study team: 2013-05-16

Who can join

Age: 18 and older. Sex: any. Healthy volunteers: not accepted.

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
Eligibility of patients receiving any medications or substances known to affect or with the potential to affect the activity or pharmacokinetics of PXD101 or 17AAG will be determined following review of their case by the Principal Investigator or Study Chair; efforts should be made to switch patients who are taking enzyme-inducing anticonvulsant agents to other medications
The effects of PXD101 and 17AAG on the developing human fetus are unknown; for this reason and because HDAC inhibitors as well as other therapeutic agents used in this trial are known to be teratogenic, women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence) 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
Ability to understand and the willingness to sign a written informed consent document
Within 4 weeks of first treatment: Left ventricular ejection fraction ≥ 45% per nuclear cardiac imaging or echocardiography

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

Where it is running

University of Wisconsin Hospital and Clinics — Madison, Wisconsin, United States

Full record on ClinicalTrials.gov

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