NCT00348985

Brief Summary

This phase I trial is studying the side effects and best dose of PXD101 and bortezomib in treating patients with advanced solid tumors or lymphomas. PXD101 and bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. PXD101 may also cause cancer cells to look more like normal cells, and to grow and spread more slowly. Giving PXD101 together with bortezomib may kill more cancer cells.

Trial Health

80
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
55

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

1 active site

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

March 1, 2006

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

July 5, 2006

Completed
1 day until next milestone

First Posted

Study publicly available on registry

July 6, 2006

Completed
3.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2010

Completed
Last Updated

May 3, 2013

Status Verified

May 1, 2013

Enrollment Period

3.8 years

First QC Date

July 5, 2006

Last Update Submit

May 1, 2013

Conditions

Adult Grade III Lymphomatoid GranulomatosisAnaplastic Large Cell LymphomaAngioimmunoblastic T-cell LymphomaExtranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid TissueIntraocular LymphomaNodal Marginal Zone B-cell LymphomaPost-transplant Lymphoproliferative DisorderPrimary Central Nervous System Hodgkin LymphomaPrimary Central Nervous System Non-Hodgkin LymphomaRecurrent Adult Burkitt LymphomaRecurrent Adult Diffuse Large Cell LymphomaRecurrent Adult Diffuse Mixed Cell LymphomaRecurrent Adult Diffuse Small Cleaved Cell LymphomaRecurrent Adult Grade III Lymphomatoid GranulomatosisRecurrent Adult Hodgkin LymphomaRecurrent Adult Immunoblastic Large Cell LymphomaRecurrent Adult Lymphoblastic LymphomaRecurrent Adult T-cell Leukemia/LymphomaRecurrent Cutaneous T-cell Non-Hodgkin LymphomaRecurrent Grade 1 Follicular LymphomaRecurrent Grade 2 Follicular LymphomaRecurrent Grade 3 Follicular LymphomaRecurrent Mantle Cell LymphomaRecurrent Marginal Zone LymphomaRecurrent Mycosis Fungoides/Sezary SyndromeRecurrent Small Lymphocytic LymphomaSplenic Marginal Zone LymphomaStage III Adult Burkitt LymphomaStage III Adult Diffuse Large Cell LymphomaStage III Adult Diffuse Mixed Cell LymphomaStage III Adult Diffuse Small Cleaved Cell LymphomaStage III Adult Hodgkin LymphomaStage III Adult Immunoblastic Large Cell LymphomaStage III Adult Lymphoblastic LymphomaStage III Adult T-cell Leukemia/LymphomaStage III Cutaneous T-cell Non-Hodgkin LymphomaStage III Grade 1 Follicular LymphomaStage III Grade 2 Follicular LymphomaStage III Grade 3 Follicular LymphomaStage III Mantle Cell LymphomaStage III Marginal Zone LymphomaStage III Mycosis Fungoides/Sezary SyndromeStage III Small Lymphocytic LymphomaStage IV Adult Burkitt LymphomaStage IV Adult Diffuse Large Cell LymphomaStage IV Adult Diffuse Mixed Cell LymphomaStage IV Adult Diffuse Small Cleaved Cell LymphomaStage IV Adult Hodgkin LymphomaStage IV Adult Immunoblastic Large Cell LymphomaStage IV Adult Lymphoblastic LymphomaStage IV Adult T-cell Leukemia/LymphomaStage IV Cutaneous T-cell Non-Hodgkin LymphomaStage IV Grade 1 Follicular LymphomaStage IV Grade 2 Follicular LymphomaStage IV Grade 3 Follicular LymphomaStage IV Mantle Cell LymphomaStage IV Marginal Zone LymphomaStage IV Mycosis Fungoides/Sezary SyndromeStage IV Small Lymphocytic LymphomaUnspecified Adult Solid Tumor, Protocol SpecificWaldenström Macroglobulinemia

Outcome Measures

Primary Outcomes (4)

  • Maximum tolerated dose of PXD101 in combination with bortezomib

    Defined as the dose level below that which results in drug-related dose limiting toxicity (DLT) in \>= 2 of 6 new patients.

    Day 21

  • Frequency and severity of treatment-related adverse events graded per NCI CTCAE version 3.0

    Day 21

  • Changes in biological markers (p21, cleaved PARP, IkB, p65 Rel A, p-AKT, p-ERK and apoptosis) from pre- to post-treatment

    Baseline and day 21

  • Objective response rate

    4 weeks

Secondary Outcomes (1)

  • Pharmacokinetics of the combination of PXD101 with bortezomib

    Baseline, end of infusion, then 15 minutes, 30 minutes, 1, 2, 4 and 6 hours from the end of infusion (days 1 and 2)

Study Arms (1)

PXD101 in Combination with Bortezomib (PS-341)

EXPERIMENTAL

Patients receive PXD101 IV over 30 minutes on days 1-5 and bortezomib IV on days 1, 4, 8, and 11 (2, 5, 8, and 11 during course 1).

Drug: belinostatDrug: bortezomibOther: pharmacological study

Interventions

belinostatDRUG
Also known as: PXD101
PXD101 in Combination with Bortezomib (PS-341)
bortezomibDRUG
Also known as: LDP 341, MLN341, VELCADE
PXD101 in Combination with Bortezomib (PS-341)
pharmacological studyOTHER
Also known as: pharmacological studies
PXD101 in Combination with Bortezomib (PS-341)

Eligibility Criteria

Age16 Years+
Sexall
Healthy VolunteersNo
Age GroupsChild (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed solid tumor or lymphoma that is refractory to standard therapy or for which no standard therapy exists
  • No active, untreated, or symptomatic brain metastases
  • Patients with treated brain metastases are eligible provided metastasis are stable and the patient is off all steroids and anticonvulsants
  • ECOG performance status 0-2
  • Life expectancy ≥ 12 weeks
  • WBC ≥ 3,000/mm\^3
  • Absolute neutrophil count ≥ 1,500/mm\^3
  • Platelet count ≥ 100,000/mm\^3
  • Bilirubin ≤ 1.5 mg/dL
  • AST and ALT ≤ 2.5 times upper limit of normal (ULN) (5 times ULN in the presence of liver metastases)
  • Creatinine ≤ 1.5 mg/dL OR creatinine clearance ≥ 60 mL/min
  • Not pregnant or nursing
  • Negative pregnancy test
  • Fertile patients must use effective contraception
  • No history of allergic reactions attributed to compounds of similar chemical or biologic composition to PXD101, bortezomib, boron, or mannitol
  • +27 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Colorado

Denver, Colorado, 80217-3364, United States

Location

MeSH Terms

Conditions

Lymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyIntraocular LymphomaLymphoma, B-Cell, Marginal ZoneBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinHodgkin DiseaseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Mantle-CellMycosis FungoidesSezary SyndromeLeukemia, Lymphocytic, Chronic, B-CellWaldenstrom Macroglobulinemia

Interventions

belinostatBortezomib

Condition Hierarchy (Ancestors)

Lymphoma, T-CellLymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphadenopathyEye NeoplasmsNeoplasms by SiteLymphoma, B-CellEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLeukemia, LymphoidLeukemiaHematologic DiseasesLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsNeoplasms, Plasma CellHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic Disorders

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic Compounds

Study Officials

  • Sue Eckhardt

    University of Colorado, Denver

    PRINCIPAL INVESTIGATOR

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 5, 2006

First Posted

July 6, 2006

Study Start

March 1, 2006

Primary Completion

January 1, 2010

Last Updated

May 3, 2013

Record last verified: 2013-05

Locations

US(1)