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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
NCIC Clinical Trials Group
ClinicalTrials.gov Identifier:
NCT00372736
First received: September 6, 2006
Last updated: January 9, 2012
Last verified: January 2012
  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 locally advanced, metastatic, or recurrent solid tumors.


Condition Intervention Phase
Unspecified Adult Solid Tumor, Protocol Specific
Drug: AEG35156
Drug: docetaxel
Genetic: protein expression analysis
Genetic: reverse transcriptase-polymerase chain reaction
Other: flow cytometry
Other: immunoenzyme technique
Other: immunohistochemistry staining method
Other: laboratory biomarker analysis
Phase 1

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Phase I Study of AEG35156 Given as a 2 Hour Intravenous Infusion in Combination With Docetaxel in Patients With Solid Tumours

Resource links provided by NLM:


Further study details as provided by NCIC Clinical Trials Group:

Primary Outcome Measures:
  • Maximum tolerated dose of AEG35156 in combination with docetaxel [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]
    Doses of AEG35156 escalated as shown in protocol section 4.3 in patient cohorts given a fixed dose of docetaxel. MTD defined as that dose level at which ≥ 2/6 patients experienced DLT (as defined in protocol section 4.6)

  • Recommended phase II dose [ Time Frame: 2-3 years ] [ Designated as safety issue: Yes ]
    RPTD for AEG35156 defined as one dose lower than MTD


Secondary Outcome Measures:
  • Toxicities [ Time Frame: Every 3 weeks ] [ Designated as safety issue: Yes ]
    Toxicities evaluated according to NCI CTCAE v3.0

  • Pharmacokinetic profile [ Time Frame: Each cycle ] [ Designated as safety issue: No ]
    Venous blood samples for determination of AEG35156 concentration obtained on all patients during cycle 1 and 2 as per protocol section 17.2

  • Antitumor activity [ Time Frame: Every 6 weeks ] [ Designated as safety issue: No ]
    All patients with measurable disease at baseline evaluated for response using RECIST criteria as described in protocol section 10.0

  • Pharmacodynamic effects of AEG35156 on X-linked inhibitor of apoptosis levels and apoptosis in peripheral blood mononuclear cells and tumor tissue [ Time Frame: Each cycle ] [ Designated as safety issue: No ]
    Venous blood samples collected for PD studies as described in protocol Section 17.0. Fresh tissue biopsies also collected in patients entered at the RPTD.

  • M30/M65 cytokeratin 18 level [ Time Frame: Each cycle ] [ Designated as safety issue: No ]
    Venous blood samples collected for determination of M30/M65 cytokeratin 18 and nucleosomal DNA as described in protocol section 17.0


Enrollment: 27
Study Start Date: June 2006
Study Completion Date: January 2012
Primary Completion Date: January 2012 (Final data collection date for primary outcome measure)
Intervention Details:
    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.
    Genetic: protein expression analysis
    Cycle 1: Pre-dose on Days -2, 1, 8 and 15; repeat every 2-4 days if LFTs > 5 x ULN1 Cycle 2: Prior to each infusion; repeat every 2-4 days if LFTs > 5 x ULN1
    Genetic: reverse transcriptase-polymerase chain reaction
    Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.
    Other: flow cytometry
    Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.
    Other: immunoenzyme technique
    Data will be summarized by descriptive statistics relevant to each of the proposed pharmacodynamic studies.
    Other: immunohistochemistry staining method
    The plasma concentration/ time data will be analysed using non-compartmental methods. The pharmacokinetic parameters to be determined for AEG35156 include the maximum observed plasma concentration (Cmax), the half-life (T1/2), and mean residence time (MRT).
    Other: laboratory biomarker analysis
    The plasma concentration/ time data will be analysed using non-compartmental methods. The pharmacokinetic parameters to be determined for AEG35156 include the maximum observed plasma concentration (Cmax), the half-life (T1/2), and mean residence time (MRT).
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

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 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
  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: NCT00372736

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 McGill Cancer Centre at McGill University
  More Information

Additional Information:
No publications provided

Responsible Party: NCIC Clinical Trials Group
ClinicalTrials.gov Identifier: NCT00372736     History of Changes
Other Study ID Numbers: I166B, CAN-NCIC-IND166B, CDR0000486837
Study First Received: September 6, 2006
Last Updated: January 9, 2012
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
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on October 19, 2014