Bortezomib and Paclitaxel in Treating Patients With Locally Advanced or Metastatic Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: paclitaxel

Drug: bortezomib

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00030368

OSU-01H0147

U01CA076576 (U.S. NIH Grant/Contract)

0158

NCI-2012-01408

CDR0000069159

NCI-1857

Details and patient eligibility

About

Phase I trial to study the effectiveness of combining bortezomib with paclitaxel in treating patients who have advanced or metastatic solid tumors. Bortezomib may stop the growth of cancer cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy work in different ways to stop tumor cells from dividing so they stop growing or die. Combining bortezomib with paclitaxel may kill more tumor cells.

Full description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose of bortezomib when given in combination with paclitaxel in patients with locally advanced or metastatic solid tumors.

OUTLINE: This is a multicenter, dose-escalation study of bortezomib.

Patients receive bortezomib IV on days 2 and 9 and paclitaxel IV over 1 hour on days 1 and 8. For the first course only, patients do not receive paclitaxel on day 1. Courses repeat every 3 weeks in the absence of disease progression or unacceptable toxicity.

Cohorts of 3-6 patients receive escalating doses of bortezomib until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity or greater than 80% 20S proteasome inhibition. Once the MTD is determined, an additional 6-9 patients are accrued and treated at that dose.

Patients are followed at 21 days.

PROJECTED ACCRUAL: A total of 45 patients will be accrued for this study.

Enrollment

45 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically or cytologically confirmed locally advanced or metastatic solid tumor for which there is no curative treatment
No known brain metastases
Performance status - ECOG 0-2
Performance status - Karnofsky 60-100%
WBC at least 3,000/mm^3
Absolute neutrophil count at least 1,500/mm^3
Platelet count at least 100,000/mm^3
Bilirubin normal
AST/ALT no greater than 2.5 times upper limit of normal (ULN)
Creatinine no greater than ULN
Left ventricular function at least lower limit of normal if received prior doxorubicin
No grade II or IV tilt-table test
No symptomatic congestive heart failure
No unstable angina pectoris
No cardiac arrhythmia
No thrombotic event within the past 6 months
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No prior allergic reaction to compounds of similar chemical or biological composition to study drugs
No other concurrent uncontrolled illness
No ongoing or active infection
No psychiatric illness or social situation that would preclude study compliance
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin)
Prior paclitaxel allowed
At least 2 weeks since prior hormonal therapy
No concurrent steroids or hormonal therapy except steroids to prevent hypersensitivity reactions to paclitaxel or hormonal therapy for non-disease-related conditions (e.g., insulin for diabetes)
At least 4 weeks since prior radiotherapy
At least 4 weeks since prior surgery
Recovered from prior therapy
No other concurrent investigational agents
No concurrent combination anti-retroviral therapy for HIV-positive patients
No concurrent anticoagulation therapy
Concurrent pamidronate or zoledronate allowed for treatment of hypercalcemia or for palliation of skeletal metastases