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Molecular Imaging With Erlotinib and Bevacizumab

Information source: Lung Cancer Group Cologne
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.

Condition(s) targeted: Non-Small-Cell Lung Carcinoma

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

Phase: Phase 2

Status: Recruiting

Sponsored by: Lung Cancer Group Cologne

Official(s) and/or principal investigator(s):
Jürgen Wolf, MD, Prof., Principal Investigator, Affiliation: Lung Cancer Group Cologne (LCGC)
Matthias Scheffler, MD, Study Chair, Affiliation: Lung Cancer Group Cologne (LCGC)
Lucia Nogova, MD, Study Chair, Affiliation: Lung Cancer Group Cologne (LCGC)

Overall contact:
Jürgen Wolf, MD, Prof., Phone: +49 221 478 89050, Email: lungenkrebs@uk-koeln.de

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

Clinical Details

Official title: Clinical Pilot to Evaluate the Accuracy of FDG-/FLT-PET and DCE-MRI for Early Prediction of Non-Progression in Patients With Advanced Non Squamous Cell Non Small Cell Lung Cancer (NSCLC) Treated With Erlotinib and Bevacizumab and to Associate Imaging Findings With Molecular Markers

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

Primary outcome: 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

Secondary outcome: 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

Eligibility

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- 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

- Patients must be able to take oral medication

- In case of female patients with childbearing potential:

- negative serum or urine HCG in women with childbearing potential

- effective method of contraception (Pearl-Index not greater than 1%)

- at least 12 months after last menstruation

Exclusion Criteria:

- Patient has received prior chemotherapeutic regimens for advanced disease. Prior

chemotherapy given as neoadjuvant or adjuvant therapy for early stage disease, completed at least 12 months prior to diagnosis of advanced stage disease, will not be considered as exclusion criterion.

- 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

- Fine needle biopsy or open biopsy within 1 week prior inclusion

- 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

- Preexisting neuropathia ≥ grade 2 • History of grade ≥2 hemoptysis (bright red blood

of at least 2. 5 ml)

- Patients undergoing renal dialysis

- Past or current history of cancer other than the entry diagnosis 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.

- Any person being in an institution on assignment of the respective authority

- Urine protein qualitative value of > 30 in urinalysis or > +1 in proteinuria testing

by dipstick

- Any medical, mental or psychological condition which in the opinion of the

investigator would not permit the patient to complete the study or understand the patient information

- Concomitant or intented anticoagulation therapy

- Planned surgical or dental invasive intervention (e. g. tooth extraction, planned

surgeries) during the course of the study

- Any serious medical condition with organ impairment

- Hypersensitivity to bevacizumab or erlotinib or any of their ingredients

- Major surgery or significant traumatic injury within the last 4 weeks before

inclusion

- Parallel participation in another clinical trial or participation in another clinical

trial within the last 30 days or 7 half-life's, whatever is of longer duration, prior study start

- Pregnancy, breast feeding

- Claustrophobia

- Known allergic reaction to Gadolinium

- Heart pacemaker

- Ferromagnetic and electronic implants in special locations (e. g. cerebral)

- Cochlea implants

- known allergic reaction to non-ionic iodinated computed tomography contrast agents

- known hyperthyroidism

Locations and Contacts

Jürgen Wolf, MD, Prof., Phone: +49 221 478 89050, Email: lungenkrebs@uk-koeln.de

Center for Integrated Oncology (CIO), University Hospital Cologne, Cologne, Northrhine-Westphalia 50924, Germany; Recruiting
Jürgen Wolf, MD, Prof., Phone: +49 221 478 89050, Email: lungenkrebs@uk-koeln.de
Matthias Scheffler, MD, Phone: +49 221 478 86127, Email: lungenkrebs@uk-koeln.de
Jürgen Wolf, MD, Prof., Principal Investigator
Matthias Scheffler, MD, Sub-Investigator
Lucia Nogova, MD, Sub-Investigator
Thomas Zander, MD, Sub-Investigator
Karin Töpelt, MD, Sub-Investigator
Christian Mattonet, MD, Sub-Investigator
Sascha Ansen, MD, Sub-Investigator
Markus Dietlein, MD, Prof., Sub-Investigator
Carsten Kobe, MD, Sub-Investigator
Matthias Schmidt, MD, Sub-Investigator
Marc Bos, MD, Sub-Investigator
Martin L. Sos, MD, Sub-Investigator
Additional Information

Starting date: January 2010
Last updated: July 1, 2011

Page last updated: August 23, 2015

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