Clinical Trial Details
— Status: Completed
Administrative data
NCT number |
NCT00708448 |
Other study ID # |
HCI26198 |
Secondary ID |
|
Status |
Completed |
Phase |
Phase 1
|
First received |
|
Last updated |
|
Start date |
March 28, 2008 |
Est. completion date |
August 12, 2010 |
Study information
Verified date |
December 2021 |
Source |
University of Utah |
Contact |
n/a |
Is FDA regulated |
No |
Health authority |
|
Study type |
Interventional
|
Clinical Trial Summary
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.
Description:
Non-Small Cell Lung Cancer Non- small cell lung cancer is the most common cause of cancer
mortality in the United States [Jermal, 2007]. Surgery can be curative for patients with
stages I and II disease and chemoradiation for curative intent can be administered to
selected patients with stage III disease in the setting of adequate performance status,
minimal comorbid disease and absence of weight loss. Adjuvant therapy improves survival, but
the relapse rate is high and may approach 80% for subsets of patients with presumed "curable
disease". Consequently, 85% of patients diagnosed with NSCLC will ultimately die of
uncontrolled systemic disease. Systemic chemotherapy for treatment of metastatic disease,
offers palliative benefit, improves survival, has substantial side effects, but is not
curative. Improved systemic therapy with a greater therapeutic index due to greater efficacy
or fewer side effects is sorely needed. Bevacizumab and/or erlotinib demonstrate these
features.
Therapeutic Drugs (Erlotinib and Bevacizumab) The therapeutic trial, which this molecular
imaging and serum biomarker trial will compliment, will study the combination of erlotinib
and bevacizumab as first-line treatment for patients with non-squamous non-small cell lung
cancer (NSCLC). This will be the first ever study where conventional chemotherapy will not be
used as first-line treatment in NSCLC. Both erlotinib, as a single agent after chemotherapy
progression [Shepherd 2005], and bevacizumab, in combination with chemotherapy [Sandler
2006], have been approved for the treatment of metastatic NSCLC. This is a multi-center trial
via Huntsman Cancer Institute - Intermountain Cancer Care Program, phase II, single stage, of
erlotinib (150 mg/day) and bevacizumab (15 mg/kg IV every 21 days) for patients with
non-squamous, NSCLC without brain metastases or significant hemoptysis who have not received
conventional chemotherapy as treatment for systemic or relapsed disease. Study treatment will
be continued until symptomatic or objective progression. Patients progressing on or after
this combination will subsequently receive conventional chemotherapy with bevacizumab at the
discretion of the patient and treating physician. The study will be followed by the Data and
Safety Monitoring Committee of the HCI and will enroll 40 patients. An interim safety
analysis is scheduled after 20 patients have been accrued.
For purposes of defining response the following criteria are used for all target lesions:
complete response-the disappearance of all target lesions; partial response-at least a 30%
decrease in the sum of the longest diameter of target lesions, taking as reference the
baseline sum longest diameter; progressive disease-at least a 20% increase in the sum of the
longest diameter of target lesions, taking as reference the smallest sum longest diameter
recorded since the treatment started or the appearance of one or more new lesions; stable
disease-neither sufficient shrinkage to qualify for partial response nor sufficient increase
to qualify for progressive disease, taking as reference the smallest sum longest diameter
since the treatment started.
The primary exploratory objectives of the study are:
- Provide a reliable and validated cadre of PET imaging derived biomarkers and serum
derived biomarkers that yield a better understanding of: 1) early clinical benefit from
Avastin and Tarceva therapy, 2) efficacy during Avastin and Tarceva therapy, and 3)
prognosis or other long term outcomes.
- Reveal a more detailed understanding of: (1) the in vivo biologic mechanisms of Avastin
and Tarceva in lung cancer and (2) information on why particular functional imaging
assays and genomic biomarker profiles are seen in treated patients.
- Reveal a more detailed understanding of how the combination of molecular imaging derived
biomarkers in combination with gene expression profiles/biomarkers will be potentially
useful to physicians for decision making and for explanation of efficacy or outcomes for
patients with cancer.
- Predict which patients may benefit from combined Avastin and Tarceva therapy.
- Determine early in the course of treatment whether Avastin and Tarceva will be
efficacious and whether the imaging derived biomarkers in combination with blood derived
biomarkers can be used in the future in patients with other types of malignancies to
predict early response and efficacy.