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

Primary Purpose

Human Mammary Carcinoma

Status
Terminated
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
AEG35156
Sponsored by
Aegera Therapeutics
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional treatment trial for Human Mammary Carcinoma focused on measuring Breast, paclitaxel, antisense, oligonucleotide

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Rocky Mountain Cancer Center
  • Cancer Centers of Florida, P.A.
  • Central Indiana Cancer Center
  • New York Oncology & Hematology P. C., Albany Cancer Center
  • Dayton Oncology & Hematology, P.A.
  • Cancer Centers of the Carolinas
  • Sammons Cancer Center
  • Tyler Cancer Center
  • Virginia Oncology Associates
  • Northwest Cancer Specialists, P. C.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

To determine progression-free survival.
To establish the pharmacokinetics of AEG35156 and paclitaxel when used in combination.

Full Information

First Posted
November 13, 2007
Last Updated
November 30, 2009
Sponsor
Aegera Therapeutics
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1. Study Identification

Unique Protocol Identification Number
NCT00558545
Brief Title
A Phase 1-2, XIAP Antisense AEG35156 With Weekly Paclitaxel in Patients With Advanced Breast Cancer
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 Type
Interventional

2. Study Status

Record Verification Date
November 2009
Overall Recruitment Status
Terminated
Why Stopped
Avastin approved for first-in-line treatment.
Study Start Date
November 2007 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Aegera Therapeutics

4. Oversight

Data Monitoring Committee
No

5. Study Description

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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Human Mammary Carcinoma
Keywords
Breast, paclitaxel, antisense, oligonucleotide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
61 (Anticipated)

8. Arms, Groups, and Interventions

Intervention Type
Drug
Intervention Name(s)
AEG35156
Intervention Description
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 Measure Information:
Title
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 Measure Information:
Title
To determine progression-free survival.
Time Frame
2 years
Title
To establish the pharmacokinetics of AEG35156 and paclitaxel when used in combination.
Time Frame
2 years

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
David M Loesch, MD
Organizational Affiliation
Central Indiana Cancer Centers
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Jacques Jolivet, MD, FACP
Organizational Affiliation
Aegera Therapeutics, Inc.
Official's Role
Study Director
Facility Information:
Facility Name
Rocky Mountain Cancer Center
City
Denver
State/Province
Colorado
ZIP/Postal Code
80218
Country
United States
Facility Name
Cancer Centers of Florida, P.A.
City
Ocoee
State/Province
Florida
ZIP/Postal Code
34761
Country
United States
Facility Name
Central Indiana Cancer Center
City
Indianapolis
State/Province
Indiana
ZIP/Postal Code
46219
Country
United States
Facility Name
New York Oncology & Hematology P. C., Albany Cancer Center
City
Albany
State/Province
New York
ZIP/Postal Code
12206
Country
United States
Facility Name
Dayton Oncology & Hematology, P.A.
City
Dayton
State/Province
Ohio
ZIP/Postal Code
45409
Country
United States
Facility Name
Cancer Centers of the Carolinas
City
Greenville
State/Province
South Carolina
ZIP/Postal Code
29605
Country
United States
Facility Name
Sammons Cancer Center
City
Dallas
State/Province
Texas
ZIP/Postal Code
75246
Country
United States
Facility Name
Tyler Cancer Center
City
Tyler
State/Province
Texas
ZIP/Postal Code
75702
Country
United States
Facility Name
Virginia Oncology Associates
City
Norfolk
State/Province
Virginia
ZIP/Postal Code
23502
Country
United States
Facility Name
Northwest Cancer Specialists, P. C.
City
Vancouver
State/Province
Washington
ZIP/Postal Code
98684
Country
United States

12. IPD Sharing Statement

Citations:
PubMed Identifier
16514137
Citation
Jemal A, Siegel R, Ward E, Murray T, Xu J, Smigal C, Thun MJ. Cancer statistics, 2006. CA Cancer J Clin. 2006 Mar-Apr;56(2):106-30. doi: 10.3322/canjclin.56.2.106.
Results Reference
background
PubMed Identifier
11709565
Citation
Perez EA, Vogel CL, Irwin DH, Kirshner JJ, Patel R. Multicenter phase II trial of weekly paclitaxel in women with metastatic breast cancer. J Clin Oncol. 2001 Nov 15;19(22):4216-23. doi: 10.1200/JCO.2001.19.22.4216.
Results Reference
background
Citation
Seidman, A., et al., CALGB 9840: Phase III study of weekly paclitaxel via 1-hour infusion versus standard 3h infusion every third week in the treatment of metastatic breast cancer (MBC), with trastuzumab (T) for HER2 positive MBC and randomized for T in HER2 normal MBC. Proc Am Soc Clin Oncol, 2004. 23: p. 6s.
Results Reference
background
PubMed Identifier
8708708
Citation
Greenberg PA, Hortobagyi GN, Smith TL, Ziegler LD, Frye DK, Buzdar AU. Long-term follow-up of patients with complete remission following combination chemotherapy for metastatic breast cancer. J Clin Oncol. 1996 Aug;14(8):2197-205. doi: 10.1200/JCO.1996.14.8.2197.
Results Reference
background

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

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