Clinical trial NCT00372736: AEG35156 and Docetaxel in Treating Patients With Locally Advanced, Metastatic, or Recurrent Solid Tumors
Official title: A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
Lead sponsor: Canadian Cancer Trials Group
Sponsor class: NETWORK
First posted: 2006-09-07
Enrollment: 27
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

Detailed 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.

Eligibility 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

Primary outcomes:
measure: Maximum tolerated dose of AEG35156 in combination with docetaxel
timeFrame: 2-3 years
measure: Recommended phase II dose
timeFrame: 2-3 years
Secondary outcomes:
measure: Toxicities
timeFrame: Every 3 weeks
measure: Pharmacokinetic profile
timeFrame: Each cycle
measure: Antitumor activity
timeFrame: Every 6 weeks
measure: Pharmacodynamic effects of AEG35156 on X-linked inhibitor of apoptosis levels and apoptosis in peripheral blood mononuclear cells and tumor tissue
timeFrame: Each cycle
measure: M30/M65 cytokeratin 18 level
timeFrame: Each cycle
Other outcomes:
Locations:
city: Vancouver
country: Canada
facility: BCCA - Vancouver Cancer Centre
state: British Columbia
city: Toronto
country: Canada
facility: Univ. Health Network-Princess Margaret Hospital
state: Ontario
city: Montreal
country: Canada
facility: McGill University - Dept. Oncology
state: Quebec
Study officials:
affiliation: McGill Cancer Centre at McGill University
name: Gerald Batist, MD
role: STUDY_CHAIR
References: