A Phase 1-2 XIAP Antisense AEG35156 With Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung Cancer

This study has been terminated.
(Unacceptable Neurotoxicity (2 cases))
Sponsor:
Information provided by:
Aegera Therapeutics
ClinicalTrials.gov Identifier:
NCT00558922
First received: November 13, 2007
Last updated: July 29, 2009
Last verified: July 2009
  Purpose

This is an open-label multicenter, phase 1-2 study. Following determination of the recommended AEG35156 dose in combination with carboplatin and 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 non small cell lung cancer.


Condition Intervention Phase
Carcinoma, Non-Small-Cell Lung
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 Carboplatin and Paclitaxel in Patients With Advanced Non-Small Cell Lung 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 carboplatin and paclitaxel and if the dose can enhance the response rate of carboplatin and paclitaxel in patients with advanced non small cell lung cancer. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine progression-free survival. [ Time Frame: 2 years ] [ Designated as safety issue: No ]

Enrollment: 54
Study Start Date: September 2007
Estimated Study Completion Date: October 2009
Estimated Primary Completion Date: August 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 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 blocking 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 down regulation has been shown to enhance taxane cytotoxicity preclinically. 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 carboplatin and paclitaxel in patients with advanced non small cell lung 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 stage IIIB (malignant pleural effusion) or stage IV non small cell lung cancer who are candidates for carboplatin and paclitaxel chemotherapy for metastatic disease
  • ECOG performance < 2
  • One or more 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 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, treatment completed at least 2 weeks prior to registration and less than 25% of the bone marrow exposed

Exclusion Criteria:

  • Prior chemotherapy for metastatic disease.
  • Patients with prior history of peripheral neuropathy
  • Patients with hypersensitivity to platinum containing compounds, mannitol or drugs formulated in Chremophor EL.
  • 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
  • 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 have received any other investigational agent within the last 30 days. 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: NCT00558922

Locations
United States, Colorado
Rocky Mountain Cancer Center
Denver, Colorado, United States, 80218
United States, Indiana
Central Indiana Cancer Center
Indianapolis, Indiana, United States, 46219
United States, Ohio
Dayton Oncology & Hematology, P.A.
Dayton, Ohio, United States, 45409
United States, South Carolina
Cancer Centers of the Carolinas
Greenville, South Carolina, United States, 29605
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Northwest Cancer Specialists, P. C.
Vancouver, Washington, United States, 98684
Sponsors and Collaborators
Aegera Therapeutics
Investigators
Principal Investigator: Robert M Jotte, MD Rocky Mountain Cancer Centers
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: NCT00558922     History of Changes
Other Study ID Numbers: AEG35156-203
Study First Received: November 13, 2007
Last Updated: July 29, 2009
Health Authority: United States: Food and Drug Administration

Keywords provided by Aegera Therapeutics:
Lung
Non small cell
antisense
oligonucleotide
paclitaxel
carboplatin

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Lung Neoplasms
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Carboplatin
Paclitaxel
X-Linked Inhibitor of Apoptosis Protein
Antimitotic Agents
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Caspase Inhibitors
Cysteine Proteinase Inhibitors
Enzyme Inhibitors
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Protease Inhibitors
Therapeutic Uses
Tubulin Modulators

ClinicalTrials.gov processed this record on October 29, 2014