AEG35156 and Docetaxel in Treating Patients With Solid Tumors

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00357747
First received: July 26, 2006
Last updated: September 16, 2011
Last verified: September 2011
  Purpose

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.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: AEG35156
Drug: docetaxel
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of AEG35156 in Combination With Docetaxel in Patients With Solid Tumors

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Safety and toxicity evaluated according to the NCI CTCAE version 3.0 [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]
  • Response and progression using RECIST criteria [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
  • 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 [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
    After completion of protocol therapy, patients with PR/CR ongoing assessed q3 months until relapse.

  • Stable disease duration measured from the time of start of therapy until the criteria for progression are met [ Time Frame: Every 3 months ] [ Designated as safety issue: No ]
    After completion of protocol therapy, patients with ongoing SD assess q 3months until progression.

  • Pharmacokinetics [ Time Frame: cycle 1 and 2 ] [ Designated as safety issue: No ]

Enrollment: 10
Study Start Date: April 2005
Study Completion Date: September 2006
Primary Completion Date: September 2006 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AEG35156 plus docetaxel Drug: AEG35156
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.
Drug: docetaxel
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.

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00357747

Locations
Canada, British Columbia
BCCA - Vancouver Cancer Centre
Vancouver, British Columbia, Canada, V5Z 4E6
Canada, Ontario
Univ. Health Network-Princess Margaret Hospital
Toronto, Ontario, Canada, M5G 2M9
Canada, Quebec
McGill University - Dept. Oncology
Montreal, Quebec, Canada, H2W 1S6
Sponsors and Collaborators
NCIC Clinical Trials Group
Investigators
Study Chair: Gerald Batist, MD Jewish General Hospital
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00357747     History of Changes
Other Study ID Numbers: I166, CAN-NCIC-IND166, CDR0000481440
Study First Received: July 26, 2006
Last Updated: September 16, 2011
Health Authority: Canada: Health Canada

Keywords provided by NCIC Clinical Trials Group:
unspecified adult solid tumor, protocol specific

Additional relevant MeSH terms:
Neoplasms
Docetaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions

ClinicalTrials.gov processed this record on July 20, 2014