Safety of Adding IMO-2055 to Erlotinib + Bevacizumab in 2nd Line Treatment for Patients With NSCLC

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
EMD Serono
ClinicalTrials.gov Identifier:
NCT00633529
First received: March 3, 2008
Last updated: October 21, 2013
Last verified: October 2013
  Purpose

To evaluate the safety of the proposed Phase II dosage of the investigational drug IMO 2055 when combined with erlotinib and bevacizumab in patients with previously treated advanced NSCLC.


Condition Intervention Phase
Non-Small Cell Lung Cancer
Drug: IMO-2055
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Open-Label Phase 1b Study of Erlotinib Plus Bevacizumab and IMO-2055 in Patients With Non-Small Cell Lung Cancer Who Have Progressed Following Initial Chemotherapy for Advanced or Metastatic Disease

Resource links provided by NLM:


Further study details as provided by EMD Serono:

Primary Outcome Measures:
  • To determine the recommended dosage of IMO-2055 when combined with erlotinib and bevacizumab in patients with AJCC stage 3 or 4 histologically proven non-small cell lung cancer (NSCLC). [ Time Frame: Assessed on a weekly basis at patient visits. ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • To evaluate the safety of weekly IMO-2055 combined with erlotinib plus bevacizumab using NCI CTCAE version 3. [ Time Frame: Assessed on a weekly basis at patient visits. ] [ Designated as safety issue: Yes ]
  • To investigate potential drug-drug interactions via a PK study, specifically the effect of IMO-2055 on the PK of bevacizumab and the PK of erlotinib and also the effect of bevacizumab and erlotinib on the PK of IMO-2055. [ Time Frame: Assessed on a weekly basis at patient visits. ] [ Designated as safety issue: Yes ]
  • To investigate potential signs of efficacy using RECIST response rate in measurable patients and PFS in all patients. [ Time Frame: Assessed every six weeks. ] [ Designated as safety issue: No ]

Enrollment: 36
Study Start Date: November 2007
Study Completion Date: March 2011
Primary Completion Date: October 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: I
Single arm: triple combination
Drug: IMO-2055
0.08, 0.16, or 0.32 mg/kg SC (subcutaneous) on days 1,8,and 15 of every 21 day cycle until evidence of progressive disease, unacceptable treatment-related toxicities, withdrawal of patient consent and/or Investigator decision to withdraw study therapy with documented reason, whichever occurs first.

Detailed Description:

Phase 1b study of escalating doses of weekly subcutaneous IMO-2055 combined with fixed standard dose regimens of oral erlotinib (daily) and IV bevacizumab (every 3 weeks) in patients with previously treated advanced NSCLC.

  Eligibility

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

Inclusion:

Patients must satisfy all the following inclusion criteria in order to be eligible for the study:

  1. Signed written informed consent
  2. AJCC stage 3 or 4 histologically proven NSCLC not amenable to curative therapy and for whom erlotinib and bevacizumab therapy would be appropriate
  3. Radiological assessment within 21 days prior to inclusion, if measurable disease is present
  4. Age ≥ 18 years
  5. ECOG performance status 0 or 1
  6. Patient has received at least one standard platinum-containing chemotherapy regimen appropriate for his/her lung cancer, in the opinion of the investigator, prior to enrollment.

Exclusion:

Patients with any of the following will be excluded from participation in the study:

Disease

  1. Squamous cell carcinoma, except for patients with no intrathoracic disease or small peripheral lesions only.
  2. Known central nervous system (CNS) metastases (Note: patients with brain metastases which have been controlled for ≥ 4 months without the use of steroid are eligible).

    Prior Treatments

  3. Less than 4 weeks between registration and the last receipt of chemotherapy, biotherapy, radiotherapy or major surgery
  4. Concurrent or planned hormonal agents such as replacement therapy, oral contraceptives, or anti-cancer therapy, e.g. Megace. (A prior history of such therapy is not exclusionary.)
  5. Administration of any investigational agent (therapeutic or diagnostic), including any investigational compound for the treatment of NSCLC, within 4 weeks prior to first study dosing Other Concomitant Medications
  6. High dose oral or intravenous corticosteroids. (Note: topical, inhaled and intra-articular corticosteroids are allowed. Prophylactic antihistamines are allowed before administration of bevacizumab
  7. Use of any medication which is a strong inhibitor or inducer of cytochrome P450 isoform CYP3A4 (see Appendix 5)
  8. Therapeutic dosing with warfarin >1 mg/day
  9. Chronic daily use of aspirin (> 325 mg/day) or other full-dose NSAIDs with anti-platelet activity
  10. Inability to take oral medication or requirement for IV alimentation or total parenteral nutrition with lipids, or prior surgical procedures affecting absorption Laboratory
  11. The following laboratory results, within 10 days of first study drug administration:

    • Hemoglobin ≤ 9.0 g/dL Absolute neutrophil count ≤ 1.5 x 109/L Platelet count ≤ 100 x 109/L
    • International Normalized Ratio (INR) > 1.3 (only if the subject is on warfarin [< 1 mg per day]) during 28 days prior to enrollment.
    • aPTT > Upper Limit of Normal (ULN) during 28 days prior to enrollment.
    • Serum creatinine ≥ 1.5 x ULN and creatinine clearance (by Cockcroft-Gault formula) <60 mL/min
    • Serum bilirubin ≥ 1.5 x ULN
    • Proteinuria: UPC ≥ 1.0 or ≥ 2+ proteinuria by urine dipstick, unless a 24-hour urine demonstrates <1.0 g/24 hours
    • ALT or AST ≥ 2.5 x ULN (≥ 5 x ULN if liver metastases)
    • Alkaline phosphatase ≥ 2.5 x ULN
    • Albumin ≤ 2.5 g/L
    • Women of child bearing potential: positive pregnancy test (serum). Other Conditions or Procedures
  12. Any clinically significant adverse events from any prior chemotherapy, surgery or radiotherapy which has not yet resolved to CTCAE v3.0 grade ≤ 1
  13. Known hypersensitivity to any oligodeoxynucleotide (ODN), EGFR-inhibitor or bevacizumab
  14. Serious, non-healing wound, ulcer or bone fracture
  15. Patients with a history or current neoplasm other than the entry diagnosis, except for curatively treated non-melanoma skin cancer or carcinoma in situ of the cervix and except for other cancers treated for cure and with a disease-free survival greater than 5 years.
  16. Pregnant or breast-feeding women
  17. Men or women of childbearing potential who refuse or who are unable to use an acceptable means of contraception
  18. History of clinically significant hemoptysis within 3 months prior to registration unless definitively treated with surgery or radiation
  19. Any medical conditions that would impose excessive risk to the patient, such as uncontrolled hypertension (systolic >150 mmHg or diastolic >100 mmHg per JNC 7 guidelines, congestive heart failure NYHA Class 2-4, uncontrolled or unstable angina, myocardial infarction within the previous 6 months, ventricular arrhythmia, infection requiring parental or oral anti-infective treatment, any altered mental status or any psychiatric condition that would interfere with understanding the informed consent, uncontrolled seizures, chronic hepatitis or cirrhosis, known human immunodeficiency virus (HIV) infection, known hepatitis B surface antigen (HBsAg) positive or uncontrolled diabetes. (Note: testing for HIV infection of HBsAg is not part of the screening assessments performed by the central laboratory).
  20. Pre-existing autoimmune or antibody-mediated diseases, including, but not limited to, the following: systemic lupus erythematosus, rheumatoid arthritis, multiple sclerosis, Sjogren's syndrome and autoimmune thrombocytopenia
  21. Evidence of bleeding diathesis or coagulopathy or other serious or acute internal bleeding within 6 months prior to registration
  22. CNS bleeding; history or clinical evidence of CNS stroke (hemorrhagic or thrombotic) within the last 6 months
  23. History of allogeneic organ transplant
  24. Brain biopsy within 12 weeks of first study dosing
  25. Minor surgical procedure, central venous catheter placement, fine needle aspirations or core biopsy within 7 days prior to first study dosing
  26. Anticipation of need for a major surgical procedure during the course of the study Other
  27. Unwilling or unable to comply with the protocol for the duration of the study
  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: NCT00633529

Locations
United States, Florida
Cancer Centers of Florida
Ocoee, Florida, United States, 34761
United States, Indiana
Central Indiana Cancer Centers
Indianapolis, Indiana, United States, 46219
United States, New York
New York Oncology Hematology P.C.
Albany, New York, United States, 12206
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75246
Cancer Therapy and Research Center
San Antonio, Texas, United States, 78229
Tyler Cancer Center
Tyler, Texas, United States, 75702
United States, Virginia
Virginia Oncology Associates
Norfolk, Virginia, United States, 23502
United States, Washington
Northwest Cancer Specialists
Vancouver, Washington, United States, 98684
Yakima Valley Memorial Hospital/North Shore Cancer Lodge
Yakima, Washington, United States, 98902
Sponsors and Collaborators
EMD Serono
Investigators
Study Director: Phil Breitfeld, MD EMD Serono
  More Information

No publications provided

Responsible Party: EMD Serono
ClinicalTrials.gov Identifier: NCT00633529     History of Changes
Other Study ID Numbers: EMR 200068-200
Study First Received: March 3, 2008
Last Updated: October 21, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by EMD Serono:
Phase 1b
Non-Small Cell Lung Cancer
Advanced or Metastatic Disease
Prior chemotherapy

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Neoplasm Metastasis
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Neoplastic Processes
Pathologic Processes
Bevacizumab
Erlotinib
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Pharmacologic Actions
Growth Inhibitors
Antineoplastic Agents
Therapeutic Uses
Protein Kinase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on July 20, 2014