AEG35156 and Docetaxel in Treating Patients With Locally Advanced, Metastatic, or Recurrent Solid Tumors

NCIC Clinical Trials Group

Status and phase

Completed

Phase 1

Conditions

Unspecified Adult Solid Tumor, Protocol Specific

Treatments

Drug: AEG35156

Genetic: protein expression analysis

Other: immunohistochemistry staining method

Other: laboratory biomarker analysis

Drug: docetaxel

Other: immunoenzyme technique

Genetic: reverse transcriptase-polymerase chain reaction

Other: flow cytometry

Study type

Interventional

Funder types

NETWORK

Identifiers

NCT00372736

CAN-NCIC-IND166B (Other Identifier)

CDR0000486837 (Other Identifier)

I166B

Details and patient eligibility

About

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.

Full description

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.

Enrollment

27 patients

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

Inclusion and exclusion 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