A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours
18 Years
N/A
Both
Unspecified Adult Solid Tumor, Protocol Specific
Trial Information
A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours
OBJECTIVES:
Primary
- Determine the maximum tolerated dose and define a recommended phase II dose of AEG35156
in combination with docetaxel in patients with locally advanced, metastatic, or
recurrent solid tumors.
Secondary
- Determine the qualitative and quantitative toxicities of AEG35156 in combination with
docetaxel given and define the duration and reversibility of those toxicities.
- Determine the pharmacokinetic profile of this regimen.
- Assess, preliminarily, the antitumor activity of this regimen in these patients.
- Assess the pharmacodynamic effects of AEG35156 on X-linked inhibitor of apoptosis
levels and apoptosis in peripheral blood mononuclear cells and in tumor tissue of these
patients.
- Evaluate M30/M65 cytokeratin 18 level (a marker of apoptosis/necrosis of epithelial
tumors) in serum of these patients.
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.
Inclusion Criteria
DISEASE CHARACTERISTICS:
- Histologically confirmed solid tumor
- Locally advanced, metastatic, or recurrent disease that is refractory to
standard curative therapy or for which no curative therapy exists
- Clinically and/or radiologically documented disease
- Treatment with single-agent docetaxel is a reasonable treatment option
- No newly diagnosed CNS metastases
- Previously treated and stable (≥ 6 months) intracranial disease allowed
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:
- Serious uncontrolled infection
- Significant cardiac dysfunction
- Significant neurological disorder that would impair the ability to obtain
informed consent
- 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
- Low-dose, nonmyelosuppressive radiotherapy allowed
- 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
- Small-volume, non-myelosuppressive palliative radiotherapy allowed
- No other concurrent experimental drugs or anticancer therapy
- No concurrent therapeutic dose anticoagulant therapy
- Non-therapeutic dose anticoagulant therapy (i.e., 1 mg daily oral warfarin)
allowed
Type of Study:
Interventional
Study Design:
Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum tolerated dose of AEG35156 in combination with docetaxel
Outcome Description:
Doses of AEG35156 escalated as shown in protocol section 4.3 in patient cohorts given a fixed dose of docetaxel. MTD defined as that dose level at which ≥ 2/6 patients experienced DLT (as defined in protocol section 4.6)
Outcome Time Frame:
2-3 years
Safety Issue:
Yes
Principal Investigator
Gerald Batist, MD
Investigator Role:
Study Chair
Investigator Affiliation:
McGill Cancer Centre at McGill University
Authority:
Canada: Health Canada
Study ID:
I166B
NCT ID:
NCT00372736
Start Date:
June 2006
Completion Date:
January 2012
Related Keywords:
- Unspecified Adult Solid Tumor, Protocol Specific
- unspecified adult solid tumor, protocol specific
- Neoplasms
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