NCT00039455

Brief Summary

Monoclonal antibodies such as trastuzumab can locate tumor cells and either kill them or deliver tumor-killing substances to them without harming normal cells. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Combining trastuzumab with flavopiridol may kill more tumor cells. Phase I trial to study the effectiveness of combining trastuzumab with flavopiridol in treating patients who have metastatic breast cancer

Trial Health

35
At Risk

Trial Health Score

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

Enrollment
50

participants targeted

Target at P50-P75 for phase_1

Geographic Reach
1 country

1 active site

Status
terminated

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

April 1, 2002

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

June 6, 2002

Completed
8 months until next milestone

First Posted

Study publicly available on registry

January 27, 2003

Completed
1.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 1, 2004

Completed
Last Updated

February 1, 2013

Status Verified

January 1, 2013

Enrollment Period

2.7 years

First QC Date

June 6, 2002

Last Update Submit

January 31, 2013

Conditions

HER2-positive Breast CancerMale Breast CancerRecurrent Breast CancerStage IV Breast Cancer

Outcome Measures

Primary Outcomes (1)

  • MTD defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity (DLT) assessed using National Cancer Institute (NCI) Common Toxicity Criteria (CTC) version 2.0

    3 weeks

Secondary Outcomes (2)

  • Measures of circulating extracellular domain of HER-2 in plasma

    Up to 3 years

  • Measures of HER-2, Cyclin D1 and activated Rb in circulating tumor cells

    Up to 3 years

Study Arms (1)

Treatment (trastuzumab and alvocidib)

EXPERIMENTAL

Patients receive trastuzumab (Herceptin) IV over 30-90 minutes on days 1, 8, and 15 followed by flavopiridol IV continuously over 24 hours on days 1 and 8. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity.

Biological: trastuzumabDrug: alvocidibOther: laboratory biomarker analysisOther: pharmacological study

Interventions

trastuzumabBIOLOGICAL

Given IV

Also known as: anti-c-erB-2, Herceptin, MOAB HER2
Treatment (trastuzumab and alvocidib)
alvocidibDRUG

Given IV

Also known as: FLAVO, flavopiridol, HMR 1275, L-868275
Treatment (trastuzumab and alvocidib)
laboratory biomarker analysisOTHER

Correlative studies

Treatment (trastuzumab and alvocidib)
pharmacological studyOTHER

Correlative studies

Also known as: pharmacological studies
Treatment (trastuzumab and alvocidib)

Eligibility Criteria

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

You may qualify if:

  • Patients must have histologically or cytologically confirmed invasive breast cancer, with stage IV disease; patients without pathologic or cytologic confirmation of metastatic disease should have unequivocal evidence of metastasis by physical exam or radiologic study
  • Either the primary tumor or the metastasis must overexpress HER2; acceptable methods of measurement of HER2 expression include immunohistochemistry (IHC) and fluorescence in situ hybridization (FISH); tumors tested by IHC must be 3+ positive for HER2 overexpression using the DAKO Herceptest or the CB-11 antibody (recently FDA approved for HER-2 testing); tumors tested by FISH must be positive by either the Vysis Pathyvision method or the Ventana INFORM method; patients may have measurable or evaluable disease
  • Patients may have received 0-3 prior chemotherapeutic regimens for metastatic breast cancer
  • Patients may have received up to two prior Herceptin-containing regimens in the metastatic setting
  • Patients may have received prior radiation therapy in either the metastatic or early stage settings; radiation therapy must be completed at least 7 days prior to study participation
  • Patients may have received hormonal therapy (therapies) in the adjuvant or metastatic setting; patients must discontinue hormonal therapy prior to study participation
  • Life expectancy of greater than 6 months
  • ECOG performance status \< 2 (Karnofsky \> 60%)
  • Absolute neutrophil count \>= 1,500/mm\^3
  • Platelets \>= 100,000/mm\^3
  • Total bilirubin =\< 1.5 mg/dl
  • AST(SGOT)/ALT(SGPT) =\< 3 X upper limit normal
  • Creatinine =\< 2.0 mg/dl
  • LVEF \>= 50%
  • EKG no acute changes
  • +3 more criteria

You may not qualify if:

  • Patients who have had more than three chemotherapy regimens in the metastatic setting, more than two Herceptin-containing regimens in the metastatic setting, radiation therapy within 1 week prior to study entry, or those who have not recovered from reversible adverse events due to prior treatments for cancer, are ineligible
  • Patients with active brain metastases or leptomengingeal carcinomatosis are excluded from this clinical trial; patients with a history of treated CNS metastases are eligible if they do not have active symptoms from their CNS disease
  • Patients with a history of grade 3 or 4 allergic reactions attributed to compounds of similar chemical or biologic composition to the agents used in the study are ineligible; patients who experienced grade 1 or 2 hypersensitivity reactions to prior Herceptin are eligible IF these reactions did not prevent further administration
  • Patients with uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements are ineligible
  • Pregnant women are excluded from this study
  • Patients with a contraindication to taking coumadin or other warfarin products are ineligible

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Dana-Farber Cancer Institute

Boston, Massachusetts, 02115, United States

Location

MeSH Terms

Conditions

Breast Neoplasms, MaleBreast Neoplasms

Interventions

Trastuzumabalvocidib

Condition Hierarchy (Ancestors)

Neoplasms by SiteNeoplasmsBreast DiseasesSkin DiseasesSkin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Antibodies, Monoclonal, HumanizedAntibodies, MonoclonalAntibodiesImmunoglobulinsImmunoproteinsBlood ProteinsProteinsAmino Acids, Peptides, and ProteinsSerum GlobulinsGlobulins

Study Officials

  • Lyndsay Harris

    Dana-Farber Cancer Institute

    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

June 6, 2002

First Posted

January 27, 2003

Study Start

April 1, 2002

Primary Completion

December 1, 2004

Last Updated

February 1, 2013

Record last verified: 2013-01

Locations

US(1)