Molecular Imaging With Erlotinib and Bevacizumab

NCT01047059 | Completed Phase 2 DMC

• 2 other identifiers: MIMEB2009-012607-26
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

The patients will be treated with erlotinib and bevacizumab for a six-week period. Imaging procedures will be performed at baseline, after one week of therapy and after the six weeks of treatment. The combination of erlotinib and bevacizumab represents an effective therapeutic strategy in NSCLC with the highest response rates ever reported for relapsed NSCLC having been observed recently in a phase II trial. Early differentiation of patients profiting and of patients not profiting from this therapy is of major relevance for further improving this targeted therapy approach and to develop more effective, personalized treatment strategies. We aim at this early identification by the combination of molecular and functional imaging tools (FDG-, FLT-PET, DCE-MRI), molecular marker analyses in tissue and peripheral blood (EGFR- and KRAS mutational status and high throughput mutational profiling in tumor tissue, angiogenesis-associated biomarkers and expression profiling in peripheral blood) and pharmokokinetic analyses. From the combined analyses of these tools we expect a better understanding of the host-drug interaction as a precondition for further improvement of erlotinib-bevacizumab combination therapy in NSCLC

Conditions

Non-Small-Cell Lung Carcinoma

Keywords

NSCLC; Lung Cancer

Outcome Measures

Primary Outcomes (1)

• To evaluate the accuracy of imaging findings in FDG-/FLT-PET and DCE-MRI after one week of treatment for early prediction of RECIST-based non-progression and progression-free survival after 6 weeks of therapy

  24 months

Secondary Outcomes (1)

• Correlation of mutational profiling with imaging characteristics Prognostic accuracy of imaging Pharmacokinetic analysis Reliability of DCE-MRI Correlation of peripheral biomarkers with clinical outcome, mutational profiling, imaging characteristics

  24 months

Study Arms (1)

Trial Intervention

EXPERIMENTAL

150mg Erlotinib daily, 15mg/kg b.w. Bevacizumab on d1, d22, d43 as medication FDG-PET, FLT-PET and DCE-MRI as diagnostical tools

Drug: Erlotinib, Bevacizumab; Drug: Fluoro-D-glucose; Drug: Fluoro-L-thymidine; Drug: Gadolinium-DPTA

Interventions

Erlotinib, Bevacizumab DRUG

Erlotinib 150mg/d d1-d43 p.o. Bevacizumab 15mg/kg b. w. d1, d22, d43 i.v.

Also known as: Tarceva, Avastin

Trial Intervention

Fluoro-D-glucose DRUG

Tracer for PET imaging

Also known as: FDG-PET

Trial Intervention

Fluoro-L-thymidine DRUG

FLT-PET tracer for imaging

Also known as: FLT-PET

Trial Intervention

Gadolinium-DPTA DRUG

Contrast agent for DCE-MRI imaging

Also known as: Gd-DPTA, Magnevist

Trial Intervention

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with histologically or cytologically proven non-squamos NSCLC stage IIIB with pleural effusion or stage IV
• ≥ 18 years of age
• Performance status ECOG 0-2
• Estimated life expectancy of at least 12 weeks
• Subjects with at least one measurable or nonmeasurable (CT or MRI) lesion according to RECIST
• Adequate bone marrow, liver and renal function as assessed by the following laboratory requirements to be conducted within 7 days prior to screening:
• Hemoglobin ≥ 9.0 g/dL
• Absolute neutrophil count (ANC) ≥ 1,500 /mm3
• Platelet count ≥ 100 000/μL
• Total bilirubin ≤ 2 x ULN
• ALT, AST and alkaline phosphatase (AP) ≤ 2,5 x ULN
• PT-INR/PTT \< 1.5 x ULN
• Creatinine clearance (CrCl) ≥ 60 ml/min calculated by either Cockcroft-Gault or by 24 hours urine collection
• Written informed consent (after adequate explanation of the trial) to participate in the trial and to adhere to trial procedures, as well as consenting to data protection procedures
• No clinical or radiological sign of interstitial lung disease, no interstitial lung disease in the past

You may not qualify if:

• Patient has received prior EGFR-targeted therapy
• Squamous-cell carcinoma (SCC) histology, SCLC histology or mixed histology
• Evidence of tumor invading or abutting major blood vessels
• Patient has signs or symptoms of acute infection requiring systemic therapy (acute or within the last 14 days)
• Uncontrolled diabetes mellitus with HbA1c \> 7,5% or elevated blood glucose levels levels of \> 200 mg/dL
• History of uncontrolled heart disease (congestive heart failure \> NYHA class 2; active Coronary Arterial Disease (CAD), (MI more than 6 months prior to study entry is allowed); cardiac arrythmias requiring anti-arrythmic therapy (except, when controlled by beta blockers or digoxin) and/or uncontrolled hypertension (\> 150/100 mmHg)
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of erlotinib and (e.g. ulcerative disease, uncontrolled nausea, vomiting, diarrhea, malabsorption syndrome or small bowel resection, total parenteral nutrition with lipids)
• History of HIV infection or previously sero-positive for the virus
• History of Hepatitis B or/and C or previously sero-positive for the Hepatitis B or/and C virus
• Patients with seizure disorder requiring CYP3A4-inducing anti-epileptics
• History of organ allograft
• Patients with evidence or history of bleeding diathesis
• History of thrombotic disorders within the last 6 months prior to enrolment
• Clinically symptomatic leptomeningeal or brain metastases (patients with clinically stable brain metastases may be enrolled)
• Impaired wound healing, non-healing wounds, ulcers, fractures or any condition that provokes uncontrolled bleeding

Sponsors & Collaborators

• University of Cologne: lead

Study Sites (1)

Center for Integrated Oncology (CIO), University Hospital Cologne

Cologne, North Rhine-Westphalia, 50924, Germany

Location

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung; Lung Neoplasms

Interventions

Erlotinib Hydrochloride; Bevacizumab; Gadolinium DTPA

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Quinazolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Antibodies, Monoclonal, Humanized; Antibodies, Monoclonal; Antibodies; Immunoglobulins; Immunoproteins; Blood Proteins; Proteins; Amino Acids, Peptides, and Proteins; Serum Globulins; Globulins; Pentetic Acid; Polyamines; Amines; Organic Chemicals; Acetates; Acids, Acyclic; Carboxylic Acids; Coordination Complexes

Study Officials

• Jürgen Wolf, MD, Prof.

  Lung Cancer Group Cologne (LCGC)

  PRINCIPAL INVESTIGATOR

• Matthias Scheffler, MD

  Lung Cancer Group Cologne (LCGC)

  STUDY CHAIR

• Lucia Nogova, MD

  Lung Cancer Group Cologne (LCGC)

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr.

Study Record Dates

• First Submitted: January 10, 2010
• First Posted: January 12, 2010
• Study Start: January 1, 2010
• Primary Completion: October 1, 2012
• Study Completion: May 1, 2016
• Last Updated: May 20, 2016

Record last verified: 2016-05

Locations

DE (1)