Doxorubicin Hydrochloride Liposome and Bortezomib in Treating Patients With Refractory Hematologic Cancer or Malignant Solid Tumor or Metastatic Breast Cancer

Phase 1

Completed

• Conditions: Leukemia; Breast Cancer; Unspecified Adult Solid Tumor, Protocol Specific; Lymphoma; Multiple Myeloma and Plasma Cell Neoplasm; Ovarian Cancer
• Interventions: Drug: PS-341; Drug: Doxil; Drug: Velcade

• Registration Number: NCT00237627
• Lead Sponsor: UNC Lineberger Comprehensive Cancer Center

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.

Detailed Description

OBJECTIVES:

Primary

* Determine the maximum tolerated dose of bortezomib when administered with pegylated doxorubicin hydrochloride liposome in patients with refractory hematologic or solid tumor malignancies. (Phase I \[closed to accrual as of 10/15/2007\])

* Determine the dose-limiting toxicity of this regimen in these patients. (Phase I \[closed to accrual as of 10/15/2007\])

* Determine the response rate in patients with metastatic breast cancer treated with this regimen. (Phase II)

Secondary

* Determine the response in patients with hematologic or solid tumor malignancies treated with this regimen. (Phase I \[closed to accrual as of 10/15/2007\])

* Determine the time to disease progression in patients with metastatic breast cancer treated with this regimen. (Phase II)

* Obtain further evidence of the safety of this regimen in patients with metastatic breast cancer. (Phase II)

OUTLINE: This is a phase I (closed to accrual as of 10/15/2007), dose-escalation study of bortezomib followed by a phase II study.

* Phase I (closed to accrual as of 10/15/2007): Patients receive bortezomib IV on days 1, 4, 8, and 11 and pegylated doxorubicin hydrochloride liposome IV over 1 hour on day 4. Treatment repeats every 21 days in the absence of disease progression or unacceptable toxicity.

* Phase II: Patients receive bortezomib (at the maximum tolerated dose determined in phase I) and pegylated doxorubicin hydrochloride liposome as in phase I.

After completion of study therapy, patients are followed at 1 week.

PROJECTED ACCRUAL: A total of 72 patients will be accrued for the phase I portion of the study and 40 for the phase II portion.

Study Timeline

• Study Start: 2001-05
• Study First Submitted: 2005-10-07
• Study First Submitted QC: 2005-10-07
• Study First Posted: 2005-10-12
• Primary Completion: 2006-12
• Study Completion: 2010-01
• Status Verified: 2012-05
• Last Update Submitted: 2012-05-16
• Last Update Posted: 2012-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 107

Inclusion Criteria

Not provided

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Exclusion Criteria

Not provided

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part 2	Velcade	Doxil + Velcade
Part 1	PS-341	Doxil + PS-341
Part 2	Doxil	Doxil + Velcade
Part 1	Doxil	Doxil + PS-341

Primary Outcome Measures

Name	Time	Method
Maximum tolerated dose (MTD) of PS-341 in combination with Doxil (Phase I)	1 year	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
Response rate of the combination of Velcade and Doxil in patients with metastatic breast cancer	every 42 days	Radiographic response will be measured using RECIST criteria

Trial Locations

Locations (1)

Lineberger Comprehensive Cancer Center at University of North Carolina - Chapel Hill; 🇺🇸 Chapel Hill, North Carolina, United States