A Phase 1-2, XIAP Antisense AEG35156 With Gemcitabine In Patients With Advanced Pancreatic Cancer

Study Overview

A Phase 1-2, XIAP Antisense AEG35156 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.

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.

Carcinoma
Pancreas

DRUG: AEG35156

AEG35156-201

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 Registration Dates	Results Reporting Dates	Study Record Updates
First Submitted 2007-11-13	Results First Submitted N/A	Last Update Submitted that met QC Criteria 2009-11-30
First Submitted that Met QC Criteria 2007-11-13	Results First Submitted that Met QC Criteria N/A	Last Update Posted (ESTIMATED) 2009-12-01
First Posted (ESTIMATED) 2007-11-14	Results First Posted N/A	Last Verified 2009-11

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

Design Details

Primary Purpose:
Treatment

Allocation:
Na

Interventional Model:
Single Group

Masking:
None

Arms and Interventions

Participant Group/Arm	Intervention/Treatment

Primary Outcome Measures	Measure Description	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		1 year

Secondary Outcome Measures	Measure Description	Time Frame
To determine progression-free survival.		2 years
To establish the pharmacokinetics of AEG35156 and gemcitabine when used in combination.		1 year

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

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.

Ages Eligible for Study:
ALL

Sexes Eligible for Study:
18 Years

Accepts Healthy Volunteers:

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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Investigators

PRINCIPAL_INVESTIGATOR: Daniel D Von Hoff, MD, FACP, TGen Clinical Research Services at Scottsdale Healthcare

Publications

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

No publications available

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Clinical Trial Record