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

Non-Small Cell Lung Cancer Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00633529
• Other study ID #: EMR 200068-200
• Status: Completed
• Phase: Phase 1
• First received: March 3, 2008
• Last updated: October 21, 2013
• Start date: November 2007
• Est. completion date: March 2011

Study information

• Verified date: October 2013
• Source: EMD Serono
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: March 2011
• Est. primary completion date: October 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years and older

Eligibility

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

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

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.

Locations

Country	Name	City	State
United States	New York Oncology Hematology P.C.	Albany	New York
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Central Indiana Cancer Centers	Indianapolis	Indiana
United States	Virginia Oncology Associates	Norfolk	Virginia
United States	Cancer Centers of Florida	Ocoee	Florida
United States	Cancer Therapy and Research Center	San Antonio	Texas
United States	Tyler Cancer Center	Tyler	Texas
United States	Northwest Cancer Specialists	Vancouver	Washington
United States	Yakima Valley Memorial Hospital/North Shore Cancer Lodge	Yakima	Washington

Sponsors (1)

Lead Sponsor	Collaborator
EMD Serono

Country where clinical trial is conducted

United States, 

References & Publications (1)

Smith, D., P. Conkling, D. Richards, C. Alemany, T. Boyd, L. Garbo, D. Loesch, D. Wages, A. Bexon, J. Murphy. Phase 1 Study of the Toll-like Receptor (TLR9) Agonist, IMO-2055, Combined with Erlotinib and Bevacizumab in Patients with Advanced or Metastatic

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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).		Assessed on a weekly basis at patient visits.	Yes
Secondary	To evaluate the safety of weekly IMO-2055 combined with erlotinib plus bevacizumab using NCI CTCAE version 3.		Assessed on a weekly basis at patient visits.	Yes
Secondary	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.		Assessed on a weekly basis at patient visits.	Yes
Secondary	To investigate potential signs of efficacy using RECIST response rate in measurable patients and PFS in all patients.		Assessed every six weeks.	No