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

This study has been terminated.
Sponsor:
Information provided by:
Aegera Therapeutics
ClinicalTrials.gov Identifier:
NCT00557596
First received: November 13, 2007
Last updated: November 30, 2009
Last verified: November 2009
  Purpose

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.


Condition Intervention Phase
Carcinoma
Pancreas
Drug: AEG35156
Phase 1
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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 Gemcitabine in Patients With Advanced Pancreatic Cancer

Resource links provided by NLM:


Further study details as provided by Aegera Therapeutics:

Primary Outcome Measures:
  • 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 ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine progression-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]
  • To establish the pharmacokinetics of AEG35156 and gemcitabine when used in combination. [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: September 2007
Estimated Study Completion Date: November 2009
Estimated Primary Completion Date: November 2009 (Final data collection date for primary outcome measure)
Intervention Details:
    Drug: AEG35156
    AEG35156 will be given as a 2-hour intravenous infusion once weekly, only on weeks when gemcitabine 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
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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
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, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00557596

Locations
United States, Arizona
Mayo Clinic Arizona
Scottsdale, Arizona, United States, 85259
Scottsdale Healthcare - SHEA
Scottsdale, Arizona, United States, 85258
Arizona Cancer Center - University of Arizona
Tucson, Arizona, United States, 85724
United States, Ohio
Gabrail Cancer Center
Canton, Ohio, United States, 44718
Sponsors and Collaborators
Aegera Therapeutics
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.
  More Information

No publications provided

Responsible Party: Jacques Jolivet, MD, Senior VP Clinical, Aegera Therapeutics Inc
ClinicalTrials.gov Identifier: NCT00557596     History of Changes
Other Study ID Numbers: AEG35156-201
Study First Received: November 13, 2007
Last Updated: November 30, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Aegera Therapeutics:
Pancreatic
antisense
oligonucleotide
gemcitabine

Additional relevant MeSH terms:
Pancreatic Neoplasms
Digestive System Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Endocrine System Diseases
Neoplasms
Neoplasms by Site
Pancreatic Diseases
Gemcitabine
X-Linked Inhibitor of Apoptosis Protein
Anti-Infective Agents
Antimetabolites
Antimetabolites, Antineoplastic
Antineoplastic Agents
Antiviral Agents
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Enzyme Inhibitors
Immunologic Factors
Immunosuppressive Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protease Inhibitors
Radiation-Sensitizing Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014