NCT00005639

Brief Summary

RATIONALE: Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining more than one drug may kill more tumor cells. PURPOSE: This phase I trial is studying the side effects and best dose of azacitidine plus phenylbutyrate in treating patients with advanced or metastatic solid tumors that have not responded to previous treatment.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
34

participants targeted

Target at P50-P75 for phase_1 lymphoma

Timeline
Completed

Started Mar 2000

Typical duration for phase_1 lymphoma

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, 2000

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

May 2, 2000

Completed
2.7 years until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
2.4 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

July 1, 2005

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

July 1, 2005

Completed
Last Updated

January 11, 2019

Status Verified

January 1, 2019

Enrollment Period

5.3 years

First QC Date

May 2, 2000

Last Update Submit

January 9, 2019

Conditions

LymphomaSmall Intestine CancerUnspecified Adult Solid Tumor, Protocol Specific

Keywords

stage III adult Hodgkin lymphomastage IV adult Hodgkin lymphomarecurrent adult Hodgkin lymphomastage III cutaneous T-cell non-Hodgkin lymphomastage IV cutaneous T-cell non-Hodgkin lymphomarecurrent cutaneous T-cell non-Hodgkin lymphomasmall intestine lymphomaunspecified adult solid tumor, protocol specificstage III grade 1 follicular lymphomastage III grade 2 follicular lymphomastage III grade 3 follicular lymphomastage III adult diffuse small cleaved cell lymphomastage III adult diffuse mixed cell lymphomastage III adult diffuse large cell lymphomastage III adult immunoblastic large cell lymphomastage III adult lymphoblastic lymphomastage III adult Burkitt lymphomastage IV grade 1 follicular lymphomastage IV grade 2 follicular lymphomastage IV grade 3 follicular lymphomastage IV adult diffuse small cleaved cell lymphomastage IV adult diffuse mixed cell lymphomastage IV adult diffuse large cell lymphomastage IV adult immunoblastic large cell lymphomastage IV adult lymphoblastic lymphomastage IV adult Burkitt lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent adult diffuse small cleaved cell lymphomarecurrent adult diffuse mixed cell lymphomarecurrent adult diffuse large cell lymphomarecurrent adult immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent adult Burkitt lymphomastage III adult T-cell leukemia/lymphomastage IV adult T-cell leukemia/lymphomarecurrent adult T-cell leukemia/lymphomaprimary central nervous system non-Hodgkin lymphomaintraocular lymphomastage III mantle cell lymphomastage IV mantle cell lymphomarecurrent mantle cell lymphomaangioimmunoblastic T-cell lymphomaanaplastic large cell lymphomastage III mycosis fungoides/Sezary syndromestage IV mycosis fungoides/Sezary syndromerecurrent mycosis fungoides/Sezary syndromerecurrent marginal zone lymphomarecurrent small lymphocytic lymphomastage III small lymphocytic lymphomastage III marginal zone lymphomastage IV small lymphocytic lymphomastage IV marginal zone lymphomaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuenodal marginal zone B-cell lymphomasplenic marginal zone lymphoma

Outcome Measures

Primary Outcomes (1)

  • Minimal Effective Dose (MED) of Azacitidine with Phenylbutyrate

    MED (milligrams) of combined Azacitidine and Phenylbutyrate that results in clinical response, as defined by Standard World Health Organization (WHO) criteria and/or target inhibition.

    up to 6 months

Secondary Outcomes (3)

  • Toxicity as assessed by number of participants experiencing adverse events Grade 3 or higher as defined by CTCAE v2.0

    up to 6 months

  • Pharmacokinetics of Azacitidine combined with Phenylbutyrate as measured by maximal plasma concentration (Cmax)

    Up to 24 hours

  • Gene-re-expression of epigenetic modulation in Peripheral Blood Mononuclear Cells (PBMC) as measured by change in Epstein-Barr Virus (EBV) viral load (number of copies per 1 million cells) after treatment with Azacitidine

    Change from baseline to up to 6 months

Study Arms (3)

Regimen A: 14-day 5-AC with intermittent phenylbutyrate

EXPERIMENTAL

Participants receive low-dose regimen of 5-AC with intermittent phenylbutyrate 400 mg/m2/day by continuous intravenous (CIV) over 24 hours on Days 6 and 13. Each cycle lasts 35 days. Cohort A1: 25 mg/m2/day subcutaneous (SC) Cohort A-1: 18.75 mg/m2/day SC Cohort A-2: 15 mg/m2/day SC Cohort A-3: 10 mg/m2/day SC

Drug: Azacitidine InjectionDrug: sodium phenylbutyrate

Regimen B: 7-day 5-AC with sequential phenylbutyrate

EXPERIMENTAL

Participants receive 5-AC 75mg/m2/day SC for 7 days, followed sequentially by two different doses of phenylbutyrate CIV starting on Day 8 and continuing for 7 days. Each cycle lasts 35 days Cohort B1: Phenylbutyrate 200 mg/m2/day CIV Cohort B2: Phenylbutyrate 400 mg/m2/day CIV

Drug: Azacitidine InjectionDrug: sodium phenylbutyrate

Regimen C: 21-day 5-AC with weekly phenylbutyrate

EXPERIMENTAL

Participants receive two different daily doses of 5-AC SC for 21 days and phenylbutyrate 400 mg/m2/day CIV over 24 hours once-per-week. Each cycle lasts 42 days. Cohort C1: 5-AC 10mg/m2/day SC Cohort C2: 5-AC 12.5mg/m2/day SC

Drug: Azacitidine InjectionDrug: sodium phenylbutyrate

Interventions

Azacitidine InjectionDRUG

subcutaneous injection (SC)

Also known as: AC, 5-AC
Regimen A: 14-day 5-AC with intermittent phenylbutyrateRegimen B: 7-day 5-AC with sequential phenylbutyrateRegimen C: 21-day 5-AC with weekly phenylbutyrate
sodium phenylbutyrateDRUG

continuous intravenous (CIV)

Regimen A: 14-day 5-AC with intermittent phenylbutyrateRegimen B: 7-day 5-AC with sequential phenylbutyrateRegimen C: 21-day 5-AC with weekly phenylbutyrate

Eligibility Criteria

Age18 Years - 120 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • DISEASE CHARACTERISTICS:
  • Histologically or cytologically confirmed locally advanced or metastatic malignant solid tumor not amenable to curative therapy
  • Lymphoma allowed
  • Progressive disease
  • Evaluable disease
  • No CNS metastases by CT scan or MRI
  • PATIENT CHARACTERISTICS:
  • Age:
  • and over
  • Performance status:
  • ECOG 0-2
  • Life expectancy:
  • Not specified
  • Hematopoietic:
  • Hemoglobin at least 8 g/dL (may be achieved by transfusion)
  • +24 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

Baltimore, Maryland, 21231, United States

Location

Related Publications (1)

  • Lin J, Gilbert J, Rudek MA, Zwiebel JA, Gore S, Jiemjit A, Zhao M, Baker SD, Ambinder RF, Herman JG, Donehower RC, Carducci MA. A phase I dose-finding study of 5-azacytidine in combination with sodium phenylbutyrate in patients with refractory solid tumors. Clin Cancer Res. 2009 Oct 1;15(19):6241-9. doi: 10.1158/1078-0432.CCR-09-0567. Epub 2009 Sep 29.

    PMID: 19789320RESULT

MeSH Terms

Conditions

LymphomaHodgkin DiseaseLymphoma, T-Cell, CutaneousLymphoma, FollicularLymphoma, Non-HodgkinLymphoma, Large B-Cell, DiffuseLymphoma, Large-Cell, ImmunoblasticPrecursor Cell Lymphoblastic Leukemia-LymphomaBurkitt LymphomaPrecursor T-Cell Lymphoblastic Leukemia-LymphomaIntraocular LymphomaLymphoma, Mantle-CellImmunoblastic LymphadenopathyLymphoma, Large-Cell, AnaplasticMycosis FungoidesSezary SyndromeLymphoma, B-Cell, Marginal ZoneLeukemia, Lymphocytic, Chronic, B-Cell

Interventions

Azacitidine4-phenylbutyric acid

Condition Hierarchy (Ancestors)

Neoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesLymphoma, T-CellLymphoma, B-CellLeukemia, LymphoidLeukemiaHematologic DiseasesEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsEye NeoplasmsNeoplasms by SiteLymphadenopathyLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aza CompoundsOrganic ChemicalsCytidinePyrimidine NucleosidesPyrimidinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsNucleosidesNucleic Acids, Nucleotides, and NucleosidesRibonucleosides

Study Officials

  • Michael A. Carducci, MD

    Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins

    STUDY CHAIR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

May 2, 2000

First Posted

January 27, 2003

Study Start

March 1, 2000

Primary Completion

July 1, 2005

Study Completion

July 1, 2005

Last Updated

January 11, 2019

Record last verified: 2019-01

Locations

US(1)