Clinical trial NCT00357747: AEG35156 and Docetaxel in Treating Patients With Solid Tumors
Official title: A Phase I Study of AEG35156 in Combination With Docetaxel in Patients With Solid Tumors
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: 2006-07-27
Enrollment: 10
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
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 solid tumors.

Detailed description: OBJECTIVES:

Primary

* Determine the maximum tolerated dose and define the recommended phase II dose of AEG35156 in combination with docetaxel in patients with solid tumors.

Secondary

* Determine the qualitative and quantitative toxicities of AEG35156 and docetaxel and define duration and reversibility of those toxicities.
* Determine the pharmacokinetic profile of this regimen.
* Assess, preliminarily, the antitumor activity of this regimen in patients with measurable disease.
* Assess the pharmacodynamic effects of AEG35156 administration on X-linked inhibitor of apoptosis protein (XIAP) levels and apoptosis in peripheral blood mononuclear cells and, in selected patients, in tumor tissue.
* Evaluate M30/M65 cytokeratin 18 level, a marker of apoptosis/necrosis of epithelial tumors, in these patients.

OUTLINE: This is a multicenter, open-label, dose-escalation study of AEG35156.

Patients receive AEG35156 IV continuously on days -2 and -1. Patients then receive AEG35156 IV continuously over 24 hours on days 1, 8, and 15. Beginning with course 2, patients also receive docetaxel IV over 1 hour on day 1. Treatment repeats every 3 weeks 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.

Blood is collected at baseline and periodically during study treatment for pharmacokinetic and pharmacodynamic assessment.

After completion of study treatment, patients are followed at 4 weeks and then every 3 months thereafter.

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 radiographically documented disease
* Docetaxel single-agent therapy must be a reasonable treatment option
* No newly diagnosed CNS metastases

  * Previously treated, intracranial disease that has been stable for ≥ 6 months allowed

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy ≥ 12 weeks
* Absolute granulocyte count ≥ 1,500/mm³
* Platelet count ≥ 100,000/mm³
* Bilirubin normal
* Creatinine normal
* AST and ALT ≤ 1.5 times upper limit of normal
* PT or INR normal
* PTT normal
* No known bleeding disorder
* No preexisting peripheral neuropathy ≥ grade 2
* No prior serious allergic reaction to taxanes (e.g., paclitaxel or docetaxel)
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* No other serious illness or medical condition that would be aggravated by treatment or preclude study requirements, including any of the following:

  * Serious uncontrolled infection
  * Significant cardiac dysfunction
  * Significant neurological disorder

PRIOR CONCURRENT THERAPY:

* No more than 2 prior chemotherapy regimens for metastatic or recurrent disease
* No more than 1 prior adjuvant chemotherapy regimen
* No more than 1 prior taxane-containing regimen
* At least 4 weeks since prior chemotherapy and recovered
* At least 4 weeks since prior external-beam radiotherapy provided \< 30% of marrow-bearing areas are irradiated\*
* At least 4 weeks since prior investigational agents or new anticancer therapy
* At least 2 weeks since prior hormonal therapy or immunotherapy
* At least 2 weeks since prior surgery and recovered
* No prior nephrectomy
* No concurrent anticoagulant therapy in therapeutic doses

  * Nontherapeutic dose anticoagulant therapy (e.g., 1 mg warfarin once daily) allowed
* No other concurrent experimental drugs or anticancer therapy
* No other concurrent cytotoxic therapy or radiotherapy

  * Small-volume, nonmyelosuppressive palliative radiotherapy allowed NOTE: \*Exceptions are made for prior low-dose non-myelosuppressive radiotherapy

Primary outcomes:
measure: Safety and toxicity evaluated according to the NCI CTCAE version 3.0
timeFrame: Every 3 weeks
measure: Response and progression using RECIST criteria
timeFrame: Every 6 weeks
measure: Response duration measured from the time complete response or partial response (whichever is first recorded) is documented until the first date that recurrent or progressive disease is objectively documented
timeFrame: Every 3 months
measure: Stable disease duration measured from the time of start of therapy until the criteria for progression are met
timeFrame: Every 3 months
measure: Pharmacokinetics
timeFrame: cycle 1 and 2
Secondary outcomes:
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: Jewish General Hospital
name: Gerald Batist, MD
role: STUDY_CHAIR
References: