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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

Phase 1/Phase 2
18 Years
Not Enrolling
Carcinoma, Non-Small-Cell Lung

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Trial Information

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

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

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

- 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

- 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

Type of Study:


Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

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.

Outcome Time Frame:

2 years

Safety Issue:


Principal Investigator

Robert M Jotte, MD

Investigator Role:

Principal Investigator

Investigator Affiliation:

Rocky Mountain Cancer Centers


United States: Food and Drug Administration

Study ID:




Start Date:

September 2007

Completion Date:

October 2009

Related Keywords:

  • Carcinoma, Non-Small-Cell Lung
  • Lung
  • Non small cell
  • antisense
  • oligonucleotide
  • paclitaxel
  • carboplatin
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



Virginia Oncology Associates Newport News, Virginia  23606
Rocky Mountain Cancer Center Denver, Colorado  80218
Cancer Centers of the Carolinas Greenville, South Carolina  29605
Central indiana Cancer Center Indianapolis, Indiana  46227
Dayton Oncology & Hematology, P.A. Kettering, Ohio  45409
Northwest Cancer Specialists, P. C. Vancouver, Washington  98684