- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00557596
A Phase 1-2, XIAP Antisense AEG35156 With Gemcitabine in Patients With Advanced Pancreatic Cancer
November 30, 2009 updated by: Aegera Therapeutics
A Phase 1-2, Multicenter, Open-Label Study of The X-Linked Inhibitor of Apoptosis (XIAP) Antisense AEG35156 Given in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer
This is an open-label multicenter, phase 1-2 study.
Following determination of the recommended AEG35156 dose in combination with gemcitabine 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 first-line in advanced pancreatic cancer.
Study Overview
Detailed Description
Apoptotic induction in cancer cells is a sought after therapeutic goal.
Most successful anticancer agents activate apoptosis pathways in the cancers they treat.
Apoptotic pathways in cells appear to converge on a single family of enzymes, the caspases, which are proteases that dismantle the cell in an orderly, non-inflammatory fashion, resulting in cell death.
The X-linked Inhibitor of Apoptosis (XIAP) is the only known cellular inhibitor of caspases, its over expression thereby blocks the principal means of apoptosis.
A wide range of evidence indicates that cellular overexpression of members of the IAP family is a fundamental means by which many cancer cells evade death, even in the presence of strong extrinsic (death receptor-mediated) and intrinsic (mitochondria-mediated) apoptotic cues.
The inhibition of cellular XIAP activity, specifically in cancer cells under stress and primed for apoptosis by chemotherapeutic agents, is viewed as a powerful means of tipping the balance towards cell death.
In particular, XIAP has been shown to be overexpressed in pancreatic cancer and to play an important role in gemcitabine resistance.
AEG35156 is a second generation antisense which targets XIAP mRNA to lower XIAP levels and the apoptotic threshold of cancer cells, enhancing their sensitivity to intrinsic death and chemotherapy.
AEG35156 may thus enhance the anticancer activity of gemcitabine in patients with advanced pancreatic cancer.
Study Type
Interventional
Enrollment (Anticipated)
48
Phase
- Phase 2
- Phase 1
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
-
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Arizona
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Scottsdale, Arizona, United States, 85259
- Mayo Clinic Arizona
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Scottsdale, Arizona, United States, 85258
- Scottsdale Healthcare - Shea
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Tucson, Arizona, United States, 85724
- Arizona Cancer Center - University of Arizona
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Ohio
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Canton, Ohio, United States, 44718
- Gabrail Cancer Center
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-
Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
Eligibility Criteria
Ages Eligible for Study
18 years and older (Adult, Older Adult)
Accepts Healthy Volunteers
No
Genders Eligible for Study
All
Description
Inclusion Criteria:
- Patients with histologically or cytologically confirmed advanced pancreatic adenocarcinoma who are candidates for first-line gemcitabine therapy
- Karnofsky performance >70%
- One or more metastatic tumors measurable by RECIST criteria on CT scan or MRI (Phase 2 part only)
- Life expectancy of at least 3 months
- Age > 18 years
- Signed, written IRB-approved informed consent
- A negative serum pregnancy test (if applicable)
- Acceptable liver function:
- Bilirubin < 1.5 times the institution's upper limit of normal
- AST (SGOT), ALT (SGPT) and Alkaline phosphatase < 2.5 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-producing potential, the use of effective contraceptive methods during the study
- Prior radiotherapy for local disease is allowed provided disease progression has been documented, and treatment completed at least 4 weeks prior to registration
Exclusion Criteria:
- Prior chemotherapy for pancreatic cancer, except for 5-fluorouracil or gemcitabine given as a radiosensitizer
- 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.
- 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
- Men who are unwilling to use acceptable forms of birth control when engaging in sexual contact with women of child bearing potential
- 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
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine the recommended dose of AEG35156 when used in combination with gemcitabine and the change in response rate of gemcitabine in patients
Time Frame: 1 year
|
1 year
|
Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
To determine progression-free survival.
Time Frame: 2 years
|
2 years
|
To establish the pharmacokinetics of AEG35156 and gemcitabine when used in combination.
Time Frame: 1 year
|
1 year
|
Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Investigators
- Principal Investigator: Daniel D Von Hoff, MD, FACP, TGen Clinical Research Services at Scottsdale Healthcare
- Study Director: Jacques Jolivet, MD, FACP, Aegera Therapeutics, Inc.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
September 1, 2007
Primary Completion (Anticipated)
November 1, 2009
Study Completion (Anticipated)
November 1, 2009
Study Registration Dates
First Submitted
November 13, 2007
First Submitted That Met QC Criteria
November 13, 2007
First Posted (Estimate)
November 14, 2007
Study Record Updates
Last Update Posted (Estimate)
December 1, 2009
Last Update Submitted That Met QC Criteria
November 30, 2009
Last Verified
November 1, 2009
More Information
Terms related to this study
Keywords
Other Study ID Numbers
- AEG35156-201
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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