NCT00007878

Brief Summary

This phase I trial studies the side effects and best dose of bortezomib when given together with fluorouracil and leucovorin calcium in treating patients with solid tumors that are metastatic or cannot be removed by surgery. Bortezomib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Drugs used in chemotherapy, such as fluorouracil and leucovorin calcium, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving bortezomib together with chemotherapy may be an effective treatment for solid tumors.

Trial Health

80
On Track

Trial Health Score

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

Enrollment
30

participants targeted

Target at P25-P50 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

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Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2000

Completed
4 months until next milestone

First Submitted

Initial submission to the registry

January 6, 2001

Completed
3.1 years until next milestone

First Posted

Study publicly available on registry

February 16, 2004

Completed
3.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

January 1, 2008

Completed
Last Updated

December 11, 2013

Status Verified

December 1, 2013

Enrollment Period

7.3 years

First QC Date

January 6, 2001

Last Update Submit

December 10, 2013

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Outcome Measures

Primary Outcomes (2)

  • MTD, defined as the highest dose tested in which none or only one patient experienced DLT attributable to the study drug(s), when at least 6 patients were treated at that dose and are evaluable for toxicity, graded according to the NCI CTC version 2.0

    Up to 21 days

  • Incidence of adverse events, graded according to NCI CTC version 2.0

    The toxicities observed at each dose level will be summarized in terms of type, severity, time of onset, duration, and reversibility or outcome. Tables will be created to summarize these toxicities and side effects by dose and course.

    Up to 7 years

Secondary Outcomes (2)

  • Survival

    Up to 7 years

  • Time to failure

    Up to 7 years

Study Arms (1)

Treatment (bortezomib, fluorouracil, leucovorin calcium)

EXPERIMENTAL

Patients receive bortezomib IV on days 1 and 4 and fluorouracil IV and leucovorin calcium IV on day 1 weekly for 2 weeks. Treatment repeats every 3 weeks in the absence of disease progression or unacceptable toxicity.

Drug: bortezomibDrug: fluorouracilDrug: leucovorin calciumOther: pharmacological studyOther: laboratory biomarker analysis

Interventions

bortezomibDRUG

Given IV

Also known as: LDP 341, MLN341, VELCADE
Treatment (bortezomib, fluorouracil, leucovorin calcium)
fluorouracilDRUG

Given IV

Also known as: 5-fluorouracil, 5-Fluracil, 5-FU
Treatment (bortezomib, fluorouracil, leucovorin calcium)
leucovorin calciumDRUG

Given IV

Also known as: CF, CFR, LV
Treatment (bortezomib, fluorouracil, leucovorin calcium)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Treatment (bortezomib, fluorouracil, leucovorin calcium)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (bortezomib, fluorouracil, leucovorin calcium)

Eligibility Criteria

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

You may qualify if:

  • Patients must have histologically or cytological confirmed malignancy which is metastatic or unresectable solid tumor for which standard curative or palliative measures do not exist or are no longer effective
  • All patients will have advanced malignancy confirmed by review of their biopsy specimens by the Division of Pathology of the City of Hope National Medical Center, the University of Southern California/LA County/Norris Comprehensive Cancer Center, or the University of California at Davis
  • Eastern Cooperative Oncology Group (ECOG) performance status =\< 2 (Karnofsky \>= 60%) and an estimated survival of at least 3 months
  • Absolute neutrophil count \>= 1,500/ul
  • Platelets \>= 100,000/ul
  • Total bilirubin =\< within the institutional normal
  • Aspartate aminotransferase (AST)/alanine aminotransferase (ALT) =\< 2.5 x the upper limits of institutional normal
  • Serum creatinine =\< 1.5 mg/dl
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control) 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

You may not qualify if:

  • Patients who have had chemotherapy, immunotherapy or radiotherapy within 4 weeks prior to entering the study and 6 weeks from nitrosourea-containing chemotherapy; all patients should have recovered from all toxicities of prior chemo and radiation therapy
  • Patients undergoing therapy with 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 toxicities
  • Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, or cardiac arrhythmia
  • Pregnant and nursing women are excluded from this study because PS-341 is an investigational agent, and the anti-proliferative activity of PS-341 may be harmful to the developing fetus or nursing infant
  • Human immunodeficiency virus HIV-positive patients receiving anti-retroviral therapy (HAART) are excluded from the study because of possible pharmacokinetic interactions
  • Patients with electrocardiogram (EKG) evidence of acute ischemia or significant conduction abnormality (bifascicular block, defined as left anterior hemiblock in the presence of right bundle branch block, 2nd or 3rd degrees atrioventricular \[AV\] blocks); any history of cardiac or cerebrovascular disease due to hypotension and tachycardia
  • Patients who had any major surgery within 2 weeks

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

University of Southern California

Los Angeles, California, 90033-0804, United States

Location

MeSH Terms

Interventions

BortezomibFluorouracilLeucovorin

Intervention Hierarchy (Ancestors)

Boronic AcidsAcids, NoncarboxylicAcidsInorganic ChemicalsBoron CompoundsOrganic ChemicalsPyrazinesHeterocyclic Compounds, 1-RingHeterocyclic CompoundsUracilPyrimidinonesPyrimidinesFormyltetrahydrofolatesTetrahydrofolatesFolic AcidPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingCoenzymesEnzymes and Coenzymes

Study Officials

  • Heinz-Josef Lenz

    University of Southern California

    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

January 6, 2001

First Posted

February 16, 2004

Study Start

September 1, 2000

Primary Completion

January 1, 2008

Last Updated

December 11, 2013

Record last verified: 2013-12

Locations

US(1)