Bortezomib and Combination Chemotherapy in Treating Patients With Advanced Solid Tumors

National Cancer Institute (NCI)

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Other: pharmacological study

Drug: etoposide

Drug: carboplatin

Drug: bortezomib

Other: laboratory biomarker analysis

Study type

Interventional

Funder types

NIH

Identifiers

NCT00027898

U01CA099176 (U.S. NIH Grant/Contract)

CDR0000069091 (Registry Identifier)

NCI-2012-02432

COMIRB 01-288

Details and patient eligibility

About

Bortezomib may stop the growth of tumor cells by blocking the enzymes necessary for their growth. Drugs used in chemotherapy use different ways to stop tumor cells from dividing so they stop growing or die. Phase I trial to study the effectiveness of combining bortezomib with carboplatin and etoposide in treating patients who have advanced solid tumors that have not responded to previous treatment

Full description

PRIMARY OBJECTIVES:

I. Determine the maximum tolerated dose (MTD) of bortezomib, carboplatin, and etoposide in patients with advanced solid tumors refractory to standard therapy.

II. Evaluate biologic effects of bortezomib on relevant targets in the tumor tissues of patients treated with this regimen.

OUTLINE: This is a dose-escalation study of bortezomib, etoposide, and carboplatin.

Patients receive bortezomib IV on days 1 and 8, carboplatin IV over 30 minutes on day 1, and etoposide IV over 60 minutes on days 1-3. Treatment repeats every 21 days for at least 2 courses 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 or more of 6 patients experience dose-limiting toxicity. Once the MTD is determined, 6 additional patients with newly diagnosed, chemotherapy-naive extensive stage small cell lung cancer, and 6 patients with other tumor types, are treated at that dose.

PROJECTED ACCRUAL: A total of 12-27 patients will be accrued for this study within 6-14 months.

Enrollment

27 patients

Sex

All

Ages

16+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria:

Histologically confirmed advanced solid tumor cancer for which no curativetherapy exists
Clinically stable CNS disease is allowed provided the following criteria are met:
- No uncontrolled brain metastases or CNS involvement
- No active seizures
- On stable dose of antiseizure or steroid medication for at least 7 days before study enrollment
Performance status - ECOG 0-2
At least 12 weeks
Absolute neutrophil count at least 1,500/mm^3
Hemoglobin at least 9 g/dL
Platelet count at least 100,000/mm^3
Bilirubin no greater than 1.5 mg/dL
AST/ALT no greater than 2.5 times upper limit of normal
Creatinine no greater than 1.5 mg/dL
Creatinine clearance at least 60 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No active infection
No other serious concurrent systemic disorders (including other malignancy)
No prior bone marrow or peripheral blood stem cell transplantation
No concurrent immunotherapy
See Disease Characteristics
At least 4 weeks since prior chemotherapy (6 weeks for nitrosoureas or mitomycin) and recovered
Prior carboplatin and/or etoposide allowed
No more than 2 prior courses of mitomycin
See Disease Characteristics
No concurrent hormonal therapy
At least 4 weeks since prior radiotherapy and recovered
Palliative radiotherapy involving less than 35% bone marrow reserve allowed if completed at least 2 weeks before study enrollment
No prior wide-field radiotherapy to 35% or more of bone marrow
No prior pelvic radiotherapy
No concurrent radiotherapy
At least 28 days since prior investigational agents
No other concurrent experimental medications