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

Sponsor

Aegera Therapeutics (Industry)

Overall Status

Terminated

CT.gov ID

NCT00558545

Collaborator

(none)

Enrollment

Locations

Duration (Months)

6.1

Patients Per Site

0.3

Patients Per Site Per Month

Study Details

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.

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 Design

Study Type:

Interventional

Anticipated Enrollment :

61 participants

Allocation:

N/A

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 :

Nov 1, 2007

Actual Primary Completion Date :

May 1, 2009

Actual Study Completion Date :

May 1, 2009

Outcome Measures

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. [2 years]

Secondary Outcome Measures

To determine progression-free survival. [2 years]
To establish the pharmacokinetics of AEG35156 and paclitaxel when used in combination. [2 years]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts 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.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Rocky Mountain Cancer Center	Denver	Colorado	United States	80218
2	Cancer Centers of Florida, P.A.	Ocoee	Florida	United States	34761
3	Central Indiana Cancer Center	Indianapolis	Indiana	United States	46219
4	New York Oncology & Hematology P. C., Albany Cancer Center	Albany	New York	United States	12206
5	Dayton Oncology & Hematology, P.A.	Dayton	Ohio	United States	45409
6	Cancer Centers of the Carolinas	Greenville	South Carolina	United States	29605
7	Sammons Cancer Center	Dallas	Texas	United States	75246
8	Tyler Cancer Center	Tyler	Texas	United States	75702
9	Virginia Oncology Associates	Norfolk	Virginia	United States	23502
10	Northwest Cancer Specialists, P. C.	Vancouver	Washington	United States	98684