NCT00237627

Brief Summary

RATIONALE: Drugs used in chemotherapy, such as doxorubicin hydrochloride liposome, work in different ways to stop the growth of cancer cells, either by killing the cells or by stopping them from dividing. Bortezomib may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Giving doxorubicin hydrochloride liposome together with bortezomib may kill more cancer cells. PURPOSE: This phase I/II trial is studying the side effects and best dose of bortezomib when given together with doxorubicin hydrochloride liposome and to see how well they work in treating patients with refractory hematologic cancer or malignant solid tumor or metastatic breast cancer.

Trial Health

87
On Track

Trial Health Score

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

Enrollment
107

participants targeted

Target at P75+ for phase_1 breast-cancer

Timeline
Completed

Started May 2001

Longer than P75 for phase_1 breast-cancer

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

May 1, 2001

Completed
4.4 years until next milestone

First Submitted

Initial submission to the registry

October 7, 2005

Completed
5 days until next milestone

First Posted

Study publicly available on registry

October 12, 2005

Completed
1.1 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2006

Completed
3.1 years until next milestone

Study Completion

Last participant's last visit for all outcomes

January 1, 2010

Completed
Last Updated

May 18, 2012

Status Verified

May 1, 2012

Enrollment Period

5.6 years

First QC Date

October 7, 2005

Last Update Submit

May 16, 2012

Conditions

Breast CancerLeukemiaLymphomaMultiple Myeloma and Plasma Cell NeoplasmOvarian CancerUnspecified Adult Solid Tumor, Protocol Specific

Keywords

stage IIIA breast cancerstage IIIB breast cancerstage IIIC breast cancerstage IV breast cancermale breast cancerrecurrent ovarian epithelial cancerstage III ovarian epithelial cancerstage IV ovarian epithelial cancerrecurrent adult acute lymphoblastic leukemiarecurrent adult acute myeloid leukemiaadult acute myeloid leukemia with 11q23 (MLL) abnormalitiesadult acute myeloid leukemia with inv(16)(p13;q22)adult acute myeloid leukemia with t(15;17)(q22;q12)adult acute myeloid leukemia with t(16;16)(p13;q22)adult acute myeloid leukemia with t(8;21)(q22;q22)secondary acute myeloid leukemiamast cell leukemiastage III chronic lymphocytic leukemiastage IV chronic lymphocytic leukemiarefractory chronic lymphocytic leukemiaT-cell large granular lymphocyte leukemiaatypical chronic myeloid leukemiaaccelerated phase chronic myelogenous leukemiablastic phase chronic myelogenous leukemiachronic phase chronic myelogenous leukemiameningeal chronic myelogenous leukemiarelapsing chronic myelogenous leukemiachronic myelomonocytic leukemiarefractory hairy cell leukemiaprogressive hairy cell leukemia, initial treatmentstage III adult T-cell leukemia/lymphomastage IV adult T-cell leukemia/lymphomarecurrent adult T-cell leukemia/lymphomastage III adult Hodgkin lymphomastage IV adult Hodgkin lymphomarecurrent adult Hodgkin lymphomaanaplastic large cell lymphomaangioimmunoblastic T-cell lymphomastage III cutaneous T-cell non-Hodgkin lymphomastage IV cutaneous T-cell non-Hodgkin lymphomastage III mycosis fungoides/Sezary syndromestage IV mycosis fungoides/Sezary syndromerecurrent cutaneous T-cell non-Hodgkin lymphomarecurrent mycosis fungoides/Sezary syndromeadult grade III lymphomatoid granulomatosisadult nasal type extranodal NK/T-cell lymphomaWaldenstrom macroglobulinemiaextranodal marginal zone B-cell lymphoma of mucosa-associated lymphoid tissuesplenic 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 immunoblastic large cell lymphomastage III adult lymphoblastic 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 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 immunoblastic large cell lymphomastage IV adult lymphoblastic 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 small lymphocytic 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 immunoblastic large cell lymphomarecurrent adult lymphoblastic lymphomarecurrent grade 1 follicular lymphomarecurrent grade 2 follicular lymphomarecurrent grade 3 follicular lymphomarecurrent mantle cell lymphomarecurrent marginal zone lymphomarecurrent small lymphocytic lymphomaintraocular lymphomaprimary central nervous system lymphomastage III multiple myelomastage II multiple myelomarefractory multiple myelomacutaneous B-cell non-Hodgkin lymphomarecurrent ovarian germ cell tumorstage III ovarian germ cell tumorstage IV ovarian germ cell tumorunspecified adult solid tumor, protocol specificrecurrent breast cancernodal marginal zone B-cell lymphoma

Outcome Measures

Primary Outcomes (2)

  • Maximum tolerated dose (MTD) of PS-341 in combination with Doxil (Phase I)

    When the current dose level exceeds the MTD, the preceding dose-level will be considered to be the MTD if there have been six patients treated at that dose level. Otherwise, 3 additional patients will be treated at the presumed MTD. No further dose escalation will occur. MTD, like dose limiting toxicity (DLT), will be defined based on toxicities seen within the first cycle. Among the additional 3 patients enrolled in a cohort, if one or more DLT is observed, the MTD will be considered to have been exceeded

    1 year

  • Response rate of the combination of Velcade and Doxil in patients with metastatic breast cancer

    Radiographic response will be measured using RECIST criteria

    every 42 days

Study Arms (2)

Part 1

EXPERIMENTAL

Doxil + PS-341

Drug: PS-341Drug: Doxil

Part 2

EXPERIMENTAL

Doxil + Velcade

Drug: DoxilDrug: Velcade

Interventions

PS-341DRUG

PS-341 will be administered as an intravenous push into a side arm of either a peripheral or central intravenous line infusing normal saline at 100 ml/hr. Patients will be treated twice weekly for two weeks, followed by a one week rest period, such that the typical days of treatment will be days 1, 4, 8, 11 of each three-week cycle. The initial dose level for PS-341 will be 0.9 mg/m2/dose intravenously, while subsequent dose levels will be determined according to a modified Fibonacci schema

Part 1
DoxilDRUG

Doxil will be administered at a dose of 30 mg/m2 as a 1 hour infusion through either a peripheral or central intravenous line every 3 weeks (on day 4 of each 21 day cycle)

Also known as: pegylated liposomal doxorubicin
Part 1Part 2
VelcadeDRUG

Velcade will be adminstered intravenously at 1.3 mg/m2 days 1, 4, 8, 11 every 3 weeks

Also known as: Bortezomib
Part 2

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)
DISEASE CHARACTERISTICS: Phase I (closed to accrual as of 10/15/2007) * Histologically or cytologically confirmed solid tumor or hematologic malignancy, including, but not limited to, any of the following: * Breast cancer * Ovarian cancer * Myeloid or lymphoid leukemia * Hodgkin or non-Hodgkin lymphoma * Multiple myeloma * Measurable or evaluable disease * Must meet 1 of the following criteria: * Refractory to at least one prior conventional treatment regimen * Not a candidate for conventional therapy * No conventional therapy exists * No clinically or radiographically significant pleural or pericardial effusion * Patients with ascites may be eligible at the discretion of the investigator * Previously treated central nervous system disease allowed provided it has been stable for \> 3 months and it is not the only site of measurable disease * Not eligible for a higher priority protocol Phase II * Diagnosis of breast cancer * Metastatic disease * Measurable disease by RECIST criteria * No symptomatic brain metastases * Patients with treated brain metastases that have been stable for \> 3 months and does not require chronic steroids are eligible * Hormone receptor status not specified PATIENT CHARACTERISTICS: Phase I (closed to accrual as of 10/15/2007) * Karnofsky performance status 60-100% * Life expectancy ≥ 2 months * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception * WBC ≥ 2,000/mm³ * ANC ≥ 1,500/mm³ (≥ 1,000/mm³ for patients with marrow infiltration) * Platelet count ≥ 100,000/mm³ (≥ 50,000/mm³ for patients with marrow infiltration) * Hemoglobin ≥ 8 g/dL * Creatinine ≤ 2.5 mg/dL OR creatinine clearance ≥ 30 mL/min * AST and ALT \< 2.5 times upper limit of normal (ULN) * Total bilirubin \< 1.2 times ULN * Prothrombin time (PT) and activated partial thromboplastin time (aPTT) \< 1.5 times ULN * Patients receiving warfarin or heparin therapy for a history of thrombosis, embolism, or other indication must have PT and/or aPTT within the accepted therapeutic ranges for those indications * Patients with a history of reactions to other liposomal drug formulations that are not due to the liposome itself may be eligible at the discretion of the investigator * No known HIV seropositivity * No known active hepatitis A, B, or C viral infection * No New York Heart Association class III or IV congestive heart failure * LVEF ≥ 45% by 2-D ECHO or MUGA * No acute ischemia or new conduction system abnormality by EKG * No conduction system abnormality (e.g., left bundle branch block) by EKG that would preclude the ability to detect new ischemic episodes * No myocardial infarction within the past 6 months * No significant comorbidity, such as poorly controlled hypertension, diabetes mellitus, or other serious medical or psychiatric illness that, in the opinion of the investigator, might compromise any aspect of the study * No uncontrolled infection * Patients may have febrile episodes up to 38.5°C if these are felt to be due to tumor fever and the possibility of infection has been ruled out by evaluation * No prior hypersensitivity reaction to pegylated doxorubicin hydrochloride liposome or doxorubicin hydrochloride * Patients with a history of reactions to other liposomal drug formulations and/or to the liposome itself, as opposed to the encapsulated agent, may be excluded at the discretion of the investigator Phase II * Female or male * Menopausal status not specified * Karnofsky performance status 70-100% * Life expectancy ≥ 3 months * Not pregnant or nursing * Negative pregnancy test * Fertile patients must use effective contraception during and for 3 months after completion of study therapy * ANC ≥ 1,500/mm³ * Platelet count ≥ 100,000/mm³ * Hemoglobin ≥ 9.0 g/dL * Creatinine ≤ 2.5 mg/dL (≤ 200 µmol/L) * AST and ALT ≤ 2 times ULN * Alkaline phosphatase ≤ 2 times ULN (unless attributed to tumor) * Bilirubin ≤ ULN * Cardiac ejection fraction \> 50% by MUGA or 2-D ECHO * No clinical evidence of congestive heart failure * No New York Heart Association class II-IV cardiac disease * No myocardial infarction within the past 6 months * No uncontrolled angina * No severe uncontrolled ventricular arrhythmias * No evidence of acute ischemia or active conduction system abnormalities by EKG * Any EKG abnormality at screening must be documented by the investigator as not medically relevant * No grade 2 peripheral neuropathy within the past 14 days * No significant comorbidity that would impair compliance with study therapy or interpretation of study results * No history of hypersensitivity reactions attributed to a conventional formulation of doxorubicin hydrochloride or the components of pegylated doxorubicin hydrochloride liposome * No hypersensitivity to bortezomib, boron, or mannitol * No serious medical or psychiatric illness likely to interfere with participation in this study PRIOR CONCURRENT THERAPY: Phase I (closed to accrual as of 10/15/2007) * More than 3 weeks since prior major surgery * More than 3 weeks since prior and no concurrent radiotherapy * More than 4 weeks since prior and no concurrent immunotherapy (i.e., interferon, interleukin, or other cytokine-based treatment) * More than 3 weeks since prior and no concurrent participation in another therapeutic clinical trial with an experimental drug * More than 3 weeks since prior and no other concurrent chemotherapy * No prior doxorubicin dose \> 400 mg/m² * No other concurrent antineoplastic therapy Phase II * More than 6 months since prior anthracyclines * More than 14 days since other prior investigational drugs * No more than 300 mg/m² of prior doxorubicin or 540 mg/m² of prior epirubicin * No more than two prior chemotherapy regimens for metastatic disease * No other concurrent antineoplastic therapy

Contact the study team to discuss eligibility requirements. They can help determine if this study is right for you.

Sponsors & Collaborators

Study Sites (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill

Chapel Hill, North Carolina, 27599-7295, United States

Location

Related Publications (1)

  • Dees EC, O'Neil BH, Lindley CM, Collichio F, Carey LA, Collins J, Riordan WJ, Ivanova A, Esseltine D, Orlowski RZ. A phase I and pharmacologic study of the combination of bortezomib and pegylated liposomal doxorubicin in patients with refractory solid tumors. Cancer Chemother Pharmacol. 2008 Dec;63(1):99-107. doi: 10.1007/s00280-008-0716-8. Epub 2008 Mar 8.

    PMID: 18327587RESULT

MeSH Terms

Conditions

Breast NeoplasmsLeukemiaLymphomaMultiple MyelomaNeoplasms, Plasma CellOvarian NeoplasmsBreast Neoplasms, MaleCarcinoma, Ovarian EpithelialPrecursor Cell Lymphoblastic Leukemia-LymphomaLeukemia, Myeloid, AcuteCongenital AbnormalitiesLeukemia, Mast-CellLeukemia, Lymphocytic, Chronic, B-CellLeukemia, Large Granular LymphocyticLeukemia, Myeloid, Chronic, Atypical, BCR-ABL NegativeLeukemia, Myeloid, Accelerated PhaseBlast CrisisLeukemia, Myeloid, Chronic-PhaseLeukemia, Myelomonocytic, ChronicLeukemia, Hairy CellPrecursor T-Cell Lymphoblastic Leukemia-LymphomaHodgkin DiseaseLymphoma, Large-Cell, AnaplasticImmunoblastic LymphadenopathyLymphoma, T-Cell, CutaneousMycosis FungoidesSezary SyndromeLymphoma, Extranodal NK-T-CellWaldenstrom MacroglobulinemiaBurkitt LymphomaLymphoma, Large B-Cell, DiffuseLymphoma, Non-HodgkinLymphoma, Large-Cell, ImmunoblasticLymphoma, FollicularLymphoma, Mantle-CellLymphoma, B-Cell, Marginal ZoneIntraocular Lymphoma

Interventions

Bortezomibliposomal doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesNeoplasms by Histologic TypeHematologic DiseasesHemic and Lymphatic DiseasesLymphoproliferative DisordersLymphatic DiseasesImmunoproliferative DisordersImmune System DiseasesHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHemorrhagic DisordersEndocrine Gland NeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersCarcinomaNeoplasms, Glandular and EpithelialLeukemia, LymphoidLeukemia, MyeloidCongenital, Hereditary, and Neonatal Diseases and AbnormalitiesMastocytosis, SystemicMastocytosisMast Cell Activation DisordersLeukemia, B-CellChronic DiseaseDisease AttributesPathologic ProcessesPathological Conditions, Signs and SymptomsLeukemia, T-CellMyelodysplastic-Myeloproliferative DiseasesBone Marrow DiseasesLeukemia, Myelogenous, Chronic, BCR-ABL PositiveMyeloproliferative DisordersCell Transformation, NeoplasticCarcinogenesisNeoplastic ProcessesLymphoma, T-CellLymphadenopathyEpstein-Barr Virus InfectionsHerpesviridae InfectionsDNA Virus InfectionsVirus DiseasesInfectionsTumor Virus InfectionsLymphoma, B-CellEye Neoplasms

Intervention Hierarchy (Ancestors)

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

Study Officials

  • Elizabeth C. Dees, MD

    UNC Lineberger Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

  • Robert Z. Orlowski, MD, PhD

    UNC Lineberger Comprehensive Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

First Submitted

October 7, 2005

First Posted

October 12, 2005

Study Start

May 1, 2001

Primary Completion

December 1, 2006

Study Completion

January 1, 2010

Last Updated

May 18, 2012

Record last verified: 2012-05

Locations

US(1)