Erlotinib and Sorafenib in Chemonaive Patients With Locally Advanced or Metastatic Non Small Cell Lung Cancer

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase II Study of Erlotinib and Sorafenib in Patients With Locally Advanced and/or Metastatic (Stage IIIb or IV) Non Small Cell Lung Cancer Who Have Not Received Prior Chemotherapy

Clinical Trial Details — Status: Active, not recruiting

Administrative data

• NCT number: NCT00722969
• Other study ID #: 07/203
• Secondary ID: EudraCT: 2007-00
• Status: Active, not recruiting
• Phase: Phase 2
• First received: July 24, 2008
• Last updated: March 2, 2009
• Start date: November 2007
• Est. completion date: April 2009

Study information

• Verified date: March 2009
• Source: Free University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Medical Ethics Review Committee (METC)Netherlands: The Central Committee on Research Involving Human Subjects (CCMO)
• Study type: Interventional

Clinical Trial Summary

Patients with advanced or metastatic (stage IIIB-IV) non small cell lung cancer who have not received prior chemotherapy will be treated with erlotinib 150 mg once a day and sorafenib 400 mg twice a day. The objectives of the study are to assess the efficacy and safety of this combination treatment. Additional exploratory study objectives are correlation of biomarkers and imaging modalities potentially predictive for response and (progression free) survival.

Recruitment information / eligibility

• Status: Active, not recruiting
• Enrollment: 48
• Est. completion date: April 2009
• Est. primary completion date: November 2008
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

Inclusion Criteria:

1. Histologically/cytologically advanced NSCLC stage IIIB or IV

2. No prior chemotherapy or therapy with systemic anti-tumor therapy (e.g., monoclonal antibody therapy) or prior exposure to agents directed at the HER axis (e.g. EGFR TK inhibitors, Herceptin). Prior surgery and/or localized irradiation is permitted provided that the irradiated lesion is not the only measurable lesion.

3. Age > 18 years.

4. ECOG Performance Status of 0 or 1

5. Life expectancy of at least 12 weeks.

6. Subjects with at least one uni-dimensional(for RECIST) measurable lesion. Lesions must be measured by CT-scan.

7. Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:

8. Hemoglobin > 9.0 g/dl

9. Absolute neutrophil count (ANC) >1,500/mm3

10. Platelet count > 100,000/µl

11. Total bilirubin < 1.5 times the upper limit of normal

12. ALT and AST < 2.5 x upper limit of normal (< 5 x upper limit of normal for patients with liver involvement of their cancer)

13. Alkaline phosphatase < 4 x ULN

14. PT-INR/PTT < 1.5 x upper limit of normal [Patients who are being therapeutically anticoagulated with low molecular weight heparin will be allowed to participate provided that no prior evidence of underlying abnormality in these parameters exists.]

15. Serum creatinine < 1.5 x upper limit of normal.

16. Written informed consent.

Exclusion Criteria:

Excluded medical conditions:

1. History of cardiac disease: congestive heart failure >NYHA class 2; active CAD (MI more than 6 mo prior to study entry is allowed); cardiac arrhythmias requiring anti-arrhythmic therapy( beta blockers or digoxin are permitted) or uncontrolled hypertension.

2. History of HIV infection or chronic hepatitis B or C.

3. Active clinically serious infections (> grade 2 NCI-CTC version 3.0)

4. Symptomatic metastatic brain or meningeal tumors (unless the patient is > 1 months from definitive radiotherapy and off steroids):

5. Patients with seizure disorder requiring medication (such as steroids or anti-epileptics)

6. History of organ allograft.

7. Patients with evidence or history of bleeding diathesis

8. Patients undergoing renal dialysis

9. Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study EXCEPT cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors [Ta, Tis & T1] or any cancer curatively treated > 3 years prior to study entry.

Excluded therapies and medications, previous and concomitant:

1. Anticancer chemotherapy or immunotherapy during the study or within 4 weeks of study entry.

2. Radiotherapy during study or within 3 weeks of start of study drug. (Palliative radiotherapy will be allowed). Major surgery within 3 weeks of start of study

3. Autologous bone marrow transplant or stem cell rescue within 4 months of study

4. Use of biologic response modifiers, such as G-CSF, within 3 week of study entry. [G-CSF and other hematopoietic growth factors may be used in the management of acute toxicity such as febrile neutropenia when clinically indicated or at the discretion of the investigator, however they may not be substituted for a required dose reduction.] [Patients taking chronic erythropoietin are permitted provided no dose adjustment is undertaken within 2 months prior to the study or during the study]

5. Investigational drug therapy outside of this trial during or within 4 weeks of study entry

6. Prior exposure to the study drugs.

7. Pregnant or breast-feeding patients. Women of childbearing potential must have a negative pregnancy test performed within 7 days of the start of treatment. Both men and women enrolled in this trial must use adequate barrier birth control measures during the course of the trial and two weeks after the completion of trial.

8. Substance abuse, medical, psychological or social conditions that may interfere with the patient's participation in the study or evaluation of the study results

9. Any condition that is unstable or could jeopardize the safety of the patient and their compliance in the study

10. Patients unable to swallow oral medications.

Study Design

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

Related Conditions & MeSH terms

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

Intervention

Drug:
• sorafenib + erlotinib
sorafenib 400mg b.i.d oral Erlotinib 150 mg o.i.d oral

Locations

Country	Name	City	State
Netherlands	Netherlands Cancer Institute	Amsterdam
Netherlands	VU university medical center	Amsterdam
Netherlands	University Medical Center Groningen	Groningen
Netherlands	University Hospital Maastricht	Maastricht

Sponsors (1)

Lead Sponsor	Collaborator
Free University Medical Center

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of non-progression at 6 weeks		6 weeks	No
Secondary	Best overall response rate		end of study	No
Secondary	Duration of response		End of study	No
Secondary	Survival		End of study	No
Secondary	Toxicity		Week 1, week 3, week 6, week 9, week 12 then every 6 weeks	Yes
Secondary	Prediction of early response and effects on tumor vascularisation by PET and perfusion CT scans		Baseline, week 3 and week 6	No
Secondary	Biomarkers for response (Proteomics, circulating cells, mutational analysis)		Baseline, week 1, week 3 and week 6	No