Early Prediction of Therapeutic Response to Targeted Therapy in Stage IIIB/IV or Recurrent Lung Cancer Patients

This study is ongoing, but not recruiting participants.
Sponsor:
Information provided by (Responsible Party):
University of Utah
ClinicalTrials.gov Identifier:
NCT00708448
First received: June 27, 2008
Last updated: July 28, 2014
Last verified: July 2014
  Purpose

This exploratory clinical study is designed to obtain pre-therapeutic imaging assessments using positron emission tomography (PET) imaging in 21 patients with Stage IIIB/IV or recurrent non-small cell lung cancer (NSCLC) and an early post therapy assessment at baseline and at various early time points (2 weeks in 7 patients, 4 weeks in 7 patients, and 6 weeks in 7 patients) after institution of erlotinib (anti-EGFR) (Tarceva) and bevacizumab (anti-VEGF) (Avastin) for first-line treatment of Stage IIIB/IV or recurrent non-squamous NSCLC. The proposed PET imaging and blood derived biomarkers trial is a companion study to an approved therapeutic trial (IRB# 24377). The therapeutic trial of erlotinib (Tarceva) and bevacizumab (Avastin) for first-line treatment of Stage IIIB/IV or recurrent lung cancer with drug costs exceeding $150,000 per patient/year (study drug budget exceeds $5 million) was funded for study at the HCI and the HICCP, statewide trial network. The proposed imaging study has been funded by the University of Utah Synergy Grant Program. The clinical imaging biomarkers will include an assessment of tumor metabolism [Banrasch 1986, Frauwirth 2002, Garber 2006, Kelloff 2005, Pauwels 1998, Semenza 2001, Smith 1999, Smith 2000, Sokoloff 1977, Warburg 1956, Weber 1977A, Weber] (dynamic FDG-PET); tumor proliferation [Rasey 2002,Shields 2001,Shields 1998, Vesselle 2002, Schwartz 2003] (dynamic FLT-PET); tumor blood flow and perfusion( H215O-PET)[Lodge 2000]; and tumor blood volume of distribution ( H215O -PET)[Lodge 2000] in the same patient at baseline and then in the same patient at one of the post therapy time points (2 weeks, 4 weeks, or 6 weeks). The investigators hypothesize that by using a set of imaging derived biomarkers and biomarkers from blood they can predict response, either prior to or at an earlier time point than would normally be determined with standard imaging techniques, in patients with lung cancer receiving combined bevacizumab and erlotinib.


Condition Intervention
Cancer
Non Small Cell Lung Cancer
Radiation: PET Imaging

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Diagnostic
Official Title: Development of an Integrated Molecular Biomarker ofEarly Prediction of Therapeutic Response to Targeted Therapy in Stage IIIB/IV or Recurrent Lung Cancer Patients Using Imaging Assessments and Genomic Modeling

Resource links provided by NLM:


Further study details as provided by University of Utah:

Primary Outcome Measures:
  • Provide reliable validated, PET imaging derived biomarkers and serum derived biomarkers for a better understanding of early clinical benefit from Avastin/Tarceva therapy, efficacy during Avastin/Tarceva therapy, and prognosis or other long term outcomes. [ Time Frame: December 2011 ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: January 2008
Estimated Study Completion Date: July 2015
Estimated Primary Completion Date: July 2015 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: All patients
All participants enrolled.
Radiation: PET Imaging
Patients will receive an FLT-PET scan, FDG-PET scan, a H215O-PET scan, and have a blood sample (15 cc, approximately 3 teaspoons) drawn for the genetic and protein studies. These studies will be done before patients begin taking erlotinib and bevacizumab.
Other Name: FLT-PET scan, FDG-PET scan, a H215O-PET scan

  Show Detailed Description

  Eligibility

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

Inclusion Criteria:

  1. All subjects must be enrolled in the the therapeutic trial (IRB # 24377) with non-squamous non-small cell lung cancer (NSCLC) treated with combined erlotinib (Tarceva) (150 mg/day)and bevacizumab (Avastin) (15mg/kg q 21 days) as first line therapy.
  2. Adults must have radiological evidence of Stage IIIB/IV or recurrent non-squamous non-small cell carcinoma. The Stage IIIB/IV or Recurrent lesion must be in a location that includes a large arterial vessel to allow for determination of the H215O arterial input function. A previous histological diagnosis of NSCLC would be required prior to institution of therapy. Only clinically indicated biopsy and/or surgery for determination of Stage IIIB/IV or recurrent disease will be done and surgery is incidental to inclusion in the protocol.
  3. Patients must be 18 years or older for inclusion in this study. Since there is no experience with [F-18]FLT in children and it would be inappropriate to study individuals under the age of 18 until more safety data is available.
  4. After entry into the study, patients are expected to be followed for at least 2 months as part of standard of care.
  5. All patients, or their legal guardians, must sign a written informed consent and HIPAA authorization in accordance with institutional guidelines.
  6. The patient, if female, must be postmenopausal for a minimum of one year or surgically sterile, or on one of the following methods of birth control for a minimum of one month prior to entry into this study: IUD, oral contraceptives, Depo-Provera or Norplant. These criteria can be waived at the discretion of the investigator if the patient's tumor is considered life threatening and the one month wait required is not in the best interest of the patient. Negative pregnancy test is accepted.
  7. Pre-treatment laboratory tests for patients receiving [F-18]FLT must be performed within 21 days prior to study entry. These must be less than 4 times below or above the upper or lower limit range for the respective laboratory test. The patients have Stage IIIB/IV or recurrent NSCLC and therefore many routine laboratory tests may not be within the typical normal range. Using a factor of 4 times above or below the upper or lower value for the normal range for laboratory test will assure ability to recruit patients and maintain safety. In those instances where a value of 4X above the normal range would be inappropriate for inclusion (prothrombin time and partial thromboplastin time) then a value of 2.5X will be used for these two laboratory tests. In those instances when the prothrombin time or partial thromboplastin time are greater than 2.5X the upper limit of normal then such a patient would not be enrolled. The 4X value will be used for all laboratory values except prothrombin time and partial thromboplastin time which cannot be above or below 2.5 times the upper or lower limit of normal (Appendix E, [F-18]FLT Laboratory Study Results). A negative serum pregnancy test is required within 2 days prior to the PET studies.
  8. Pre-treatment radiological clinical scans/studies (Gd- enhanced MRI or CT to document Stage IIIB/IV or recurrent NSCLC) must be performed within 30 days of study entry.

Exclusion Criteria:

  1. Patients will be receiving erlotinib (Tarceva) (150 mg/day)and bevacizumab (Avastin) (15mg/kg q 21 days) as part of the therapeutic trial. Enrollment may not occur if the patient does not meet the enrollment criteria for the therapeutic trial
  2. Patients with known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals. Patients with significant drug or other allergies or autoimmune diseases may be enrolled at the Investigator's discretion.
  3. Patients who are pregnant or lactating or who suspect they might be pregnant.
  4. Adult patients who require monitored anesthesia for PET scanning.
  5. HIV positive patients due to the previous toxicity noted with FLT.
  6. Claustrophobia or inability to remain stationary within the PET scanner for 90 minutes.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00708448

Locations
United States, Utah
Huntsman Cancer Institute
Salt Lake City, Utah, United States, 84112
Sponsors and Collaborators
University of Utah
Investigators
Principal Investigator: John M Hoffman, MD Huntsman Cancer Institute
  More Information

Additional Information:
No publications provided

Responsible Party: University of Utah
ClinicalTrials.gov Identifier: NCT00708448     History of Changes
Other Study ID Numbers: HCI26198
Study First Received: June 27, 2008
Last Updated: July 28, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Utah:
NSCLC

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

ClinicalTrials.gov processed this record on September 22, 2014