A Phase 1-2, XIAP Antisense AEG35156 With Weekly Paclitaxel in Patients With Advanced Breast Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00558545
Recruitment Status : Terminated (Avastin approved for first-in-line treatment.)
First Posted : November 15, 2007
Last Update Posted : December 2, 2009
Information provided by:
Aegera Therapeutics

Brief Summary:
This is an open-label multicenter, phase 1-2 study. Following determination of the recommended AEG35156 dose in combination with weekly paclitaxel in the initial Phase 1 part of this study, additional patients will be enrolled in the Phase 2 part of the study to assess the activity of the combination in advanced breast cancer.

Condition or disease Intervention/treatment Phase
Human Mammary Carcinoma Drug: AEG35156 Phase 1 Phase 2

Detailed Description:
Breast cancer is the most common cancer in women in the United States, the second most common cause of cancer death, and the main cause of death in women ages 45 to 55. In 2006, 212,920 American women will be diagnosed with breast cancer, and 40,970 will die from this disease.[1]. Fewer than 10 percent of women present with metastatic disease at the time of diagnosis. However, the majority of women who relapse after initial definitive therapy for early stage or locally advanced disease will do so with disseminated metastatic disease rather than an isolated local recurrence. Treatment for metastatic disease is palliative in intent and will usually involve hormone therapy and/or chemotherapy with or without trastuzumab. Active chemotherapy agents include anthracyclines, taxanes, vinorelbine, alkylating agents and antimetabolites. Taxanes have become the cornerstone of first-line treatment for metastatic breast cancer. Weekly doses of paclitaxel can be administered continuously for several weeks with a remarkable lack of myelosuppression [2]. Weekly paclitaxel (80 mg/m2) was directly compared to every three-week therapy (175 mg/m2) in 585 women with metastatic breast cancer. Weekly therapy was associated with a significantly higher response rate (40 versus 28 percent) and longer TTP (nine versus five months), but similar overall survival and worse neurotoxicity [3]. Since patients with metastatic breast cancer are unlikely to be cured of their disease [4], they should be considered candidates for a clinical trial.

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 61 participants
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: A Phase 1-2, Multicenter, Open-Label Study of the X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With Weekly Paclitaxel in Patients With Advanced Breast Cancer
Study Start Date : November 2007
Actual Primary Completion Date : May 2009
Actual Study Completion Date : May 2009

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Breast Cancer
Drug Information available for: Paclitaxel
U.S. FDA Resources

Intervention Details:
    Drug: AEG35156
    AEG35156 will be given as a 2-hour intravenous infusion once weekly only on weeks when paclitaxel is administered, with a 2-hour loading dose given daily in the 2 days immediately prior to Day 1 (on Days -2 and -1) only in Cycle 1.

Primary Outcome Measures :
  1. To determine the recommended dose of AEG35156 when used in combination with weekly paclitaxel and at the dose enhance the clinical benefit rate (CBR) of paclitaxel in patients with advanced breast cancer. [ Time Frame: 2 years ]

Secondary Outcome Measures :
  1. To determine progression-free survival. [ Time Frame: 2 years ]
  2. To establish the pharmacokinetics of AEG35156 and paclitaxel when used in combination. [ Time Frame: 2 years ]

Information from the National Library of Medicine

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, Learn About Clinical Studies.

Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion Criteria:

  • Patients with histologically or cytologically confirmed breast adenocarcinoma who are candidates for paclitaxel single agent chemotherapy for metastatic breast cancer
  • ECOG performance < 2
  • One or more metastatic tumors measurable by RECIST criteria on CT scan or MRI (Phase 2 part only)
  • Life expectancy of at least 6 months
  • Age > 18 years
  • Signed, written IRB-approved informed consent
  • A negative serum pregnancy test (if applicable)
  • Acceptable liver function:
  • Bilirubin within normal limit
  • AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 2.0 times the institution's upper limit of normal
  • Acceptable renal function:
  • Serum creatinine within normal limits, OR calculated creatinine clearance > 60 mL/min/1.73 m2 for patients with creatinine levels above institutional normal
  • Acceptable hematologic status:
  • Granulocyte > 1500 cells/uL
  • Platelet count > 100,000 plt/uL
  • Hemoglobin > 9.0 g/dL
  • Acceptable coagulation status:
  • PT within normal limits
  • PTT within normal limits
  • For women of child-bearing potential, the use of effective contraceptive methods during the study
  • Prior radiotherapy is allowed provided disease progression outside the radiation field has been documented, and treatment completed at least 2 weeks prior to registration

Exclusion Criteria:

  • Prior taxane chemotherapy for metastatic disease.
  • More than one prior chemotherapy regimen for metastatic disease
  • Active progressive brain metastases including the presence of any related symptoms or need for corticosteroids. A CT or MRI scan of the head is necessary in patients with a history of brain metastases to document the stability of prior lesions
  • Grade > 2 peripheral neuropathy
  • Known bleeding diathesis or concurrent treatment with anticoagulants except patients on non-therapeutic line maintenance coumadin
  • Pregnant or nursing women. NOTE: Women of child-bearing potential must agree to use adequate contraception (sterile or surgically sterile; hormonal or barrier method of birth control; or abstinence) prior to study entry and for the duration of study participation. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately
  • Active, uncontrolled bacterial, viral, or fungal infections, requiring systemic therapy
  • Known infection with HIV, hepatitis B, or hepatitis C
  • Serious nonmalignant disease that could compromise protocol objectives in the opinion of the investigator and/or the sponsor
  • Patients who are currently receiving any other investigational agent. Subjects who have used a previous antisense oligonucleotide in the last 90 days will be excluded
  • Unwillingness or inability to comply with procedures required in this protocol
  • Any deviation from these inclusion/exclusion criteria must be discussed with the sponsor prior to enrolling patient.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its identifier (NCT number): NCT00558545

United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Florida
Cancer Centers of Florida, P.A.
Ocoee, Florida, United States, 34761
United States, Indiana
Central Indiana Cancer Center
Indianapolis, Indiana, United States, 46219
United States, New York
New York Oncology & Hematology P. C., Albany Cancer Center
Albany, New York, United States, 12206
United States, Ohio
Dayton Oncology & Hematology, P.A.
Dayton, Ohio, United States, 45409
United States, South Carolina
Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Texas
Sammons Cancer Center
Dallas, Texas, United States, 75246
Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Northwest Cancer Specialists, P. C.
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Aegera Therapeutics
Principal Investigator: David M Loesch, MD Central Indiana Cancer Centers
Study Director: Jacques Jolivet, MD, FACP Aegera Therapeutics, Inc.

Responsible Party: Jacques Jolivet, VP Clinical, Aegera Therapeutics Inc. Identifier: NCT00558545     History of Changes
Other Study ID Numbers: AEG35156-202
First Posted: November 15, 2007    Key Record Dates
Last Update Posted: December 2, 2009
Last Verified: November 2009

Keywords provided by Aegera Therapeutics:

Additional relevant MeSH terms:
Breast Neoplasms
Neoplasms by Site
Breast Diseases
Skin Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action