AEG35156 and Docetaxel in Treating Patients With Solid Tumors

Study Overview
=================
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.

Official Title
-----------------
A Phase I Study of AEG35156 in Combination With Docetaxel in Patients With Solid Tumors

Conditions
-----------------
Unspecified Adult Solid Tumor, Protocol Specific

Intervention / Treatment
-----------------
* Drug: AEG35156
* Drug: docetaxel


Participation Criteria
=================
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 120 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AEG35156 plus docetaxel<br> | Drug: AEG35156<br>* After a recommended phase II dose (RPTD) of AEG35156 has been determined with docetaxel 75 mg/m2, patients will be accrued to the RPTD-1 plus docetaxel 100 mg/m2, and possibly RPTD plus docetaxel 100 mg/m2, to determine the RPTD of AEG35156 in combination with docetaxel 100 mg/m2 given every three weeks.<br>Drug: docetaxel<br>* After a recommended phase II dose (RPTD) of AEG35156 has been determined with docetaxel 75 mg/m2, patients will be accrued to the RPTD-1 plus docetaxel 100 mg/m2, and possibly RPTD plus docetaxel 100 mg/m2, to determine the RPTD of AEG35156 in combination with docetaxel 100 mg/m2 given every three weeks.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Safety and toxicity evaluated according to the NCI CTCAE version 3.0 |  | Every 3 weeks | 
| Response and progression using RECIST criteria |  | Every 6 weeks | 
| 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 | After completion of protocol therapy, patients with PR/CR ongoing assessed q3 months until relapse. | Every 3 months | 
| Stable disease duration measured from the time of start of therapy until the criteria for progression are met | After completion of protocol therapy, patients with ongoing SD assess q 3months until progression. | Every 3 months | 
| Pharmacokinetics |  | cycle 1 and 2 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
unspecified adult solid tumor, protocol specific