A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours
A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours
RATIONALE: Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. AEG35156 may help docetaxel work better by making tumor cells more sensitive to the drug.
PURPOSE: This phase I trial is studying the side effects and best dose of AEG35156 when given together with docetaxel in treating patients with locally advanced, metastatic, or recurrent solid tumors.
OBJECTIVES:
Primary
Secondary
OUTLINE: This is a multicenter, open-label, dose-escalation study of AEG35156.
Patients receive AEG35156 IV over 2 hours on days -1, 0, 1, 8, and 15 during course 1 and on days 1, 8, and 15 of all subsequent courses. Patients also receive docetaxel IV over 1 hour on day 1. Treatment repeats every 21 days for up to 6 courses in the absence of disease progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of AEG35156 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. Additional patients receive AEG35156 at the recommended phase II dose (RPTD).
Blood is drawn periodically for pharmacokinetic and pharmacodynamic studies. Samples are examined by flow cytometry, immunoenzyme methods, and reverse transcriptase-polymerase chain reaction for biological markers. Tumor tissue (archival and fresh) is collected from patients treated at the RPTD and examined by immunohistochemical methods and biological marker analysis.
After completion of study treatment, all patients are followed at 4 weeks. Patients with response or stable disease ongoing are followed every 3 months thereafter until relapse/progression. Patients with protocol-related toxicity also followed q 3 months until resolution to ≤ grade 2.
PROJECTED ACCRUAL: A total of 30 patients will be accrued for this study.
DISEASE CHARACTERISTICS:
Histologically confirmed solid tumor
Clinically and/or radiologically documented disease
Treatment with single-agent docetaxel is a reasonable treatment option
No newly diagnosed CNS metastases
PATIENT CHARACTERISTICS:
ECOG performance status 0-2
Life expectancy ≥ 12 weeks
Absolute granulocyte count ≥ 1,500/mm³
Platelet count ≥ 100,000/mm³
PT or INR and PTT normal
Creatinine normal
Bilirubin normal
AST and ALT ≤ 1.5 times upper limit of normal (ULN)
Gamma-glutamyl transferase ≤ 3 times ULN
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception
No underlying serious illness or medical condition that might be aggravated by treatment or might interfere with study treatment, including, but not limited to, the following:
No known bleeding disorders
No prior serious allergic reaction to taxane (paclitaxel or docetaxel)
No pre-existing peripheral neuropathy ≥ grade 2
PRIOR CONCURRENT THERAPY:
More than 4 weeks since prior chemotherapy and recovered
At least 2 weeks since prior hormonal therapy or immunotherapy
At least 4 weeks since prior external-beam radiotherapy to < 30% of marrow-bearing areas
At least 2 weeks since prior surgery and recovered
More than 4 weeks since prior investigational agents or new anticancer therapy
No prior nephrectomy
No other concurrent chemotherapy
No concurrent radiotherapy
No other concurrent experimental drugs or anticancer therapy
No concurrent therapeutic dose anticoagulant therapy