Re: This Week's NCI Cancer Bulletin: Oct. 21, 2008

"E. Nigma" wrote:

Cancer.gov Update
Research Portfolio Offers More Information, New Tools

Special Report
Lung Cancer and Erlotinib: Which Patients Benefit?

Featured Clinical Trial

NCI Launches First-Ever Study to Determine if Biomarkers Can Help Guide
Treatment for Lung Cancer

Today, a large national clinical trial for non-small cell lung cancer was
launched to validate whether a biomarker can predict clinical benefit in
the treatment of this disease. Biomarkers, which are molecules found in
the body that can signal an abnormal process or disease, would identify a
target known as epidermal growth factor receptor (EGFR). This receptor can
be increased in some lung cancers due to the presence of extra copies of
its coding gene. These extra copies can result in activation of tumor
growth, so drugs that block this activation could have a significant
impact on lung cancer treatment. This study, sponsored by the National
Cancer Institute (NCI), part of the National Institutes of Health, is
called MARVEL (Marker Validation for Erlotinib in Lung Cancer) and will
attempt to definitively establish the future value of selecting patients
for treatment based on the presence or absence of EGFR activation.

Approximately 1,200 lung cancer patients will be tested for the status of
this biomarker, and then will be randomly assigned to treatment based on
the test results. Both EGFR-positive and EGFR-negative patients will
receive either the chemotherapy drugs erlotinib (Tarceva ®, Genentech) or
pemetrexed (Alimta ®, Eli Lilly) after they have received their initial,
standard chemotherapy. Erlotinib specifically targets EGFR, whereas
pemetrexed blocks tumor cell growth by another mechanism.

It is hypothesized that erlotinib will be superior in the patients with
EGFR-positive lung cancer, whereas pemetrexed would be favored in patients
with EGFR-negative lung cancer, based on knowledge from earlier, smaller
studies. MARVEL will incorporate genetic studies for erlotinib and
pemetrexed that will be important to further identify patients with
different sensitivity and toxicity profiles to these therapies.

Lung cancer is expected to claim 161,840 lives in 2008, and 215,020 people
are expected to be diagnosed with the disease this year, making it the
number one cancer killer. Non-small cell lung cancer represents about 85
to 90 percent of all lung cancers.

"Because lung cancer is such a lethal disease and because it is
particularly difficult to treat, especially if diagnosed in its later
stages, the MARVEL trial is of major importance because it could define,
based on a single test, the best therapy for this disease. The future of
moving highly targeted agents from the lab to the clinic will be heavily
dependent on biomarkers for patient selection," said NCI director John E.
Niederhuber, M.D.

Both erlotinib and pemetrexed are approved treatments for advanced
non-small cell lung cancer. Among the factors that appear to influence
responsiveness to erlotinib, in addition to the level of EGFR activation,
are whether the resulting cancer cells are classified as adenocarcinomas
(as opposed to squamous or other types of cells), female gender, Asian
ethnicity, and whether the patient was ever a smoker. However, no
forward-looking study has been performed to definitively address which
factors are most important.

MARVEL, also known as N0723, is a phase III study that will be led by the
North Central Cancer Treatment Group (NCCTG) and include many other
NCI-sponsored clinical trial groups. The trial will enroll patients over a
four year period and test them for EGFR status. It will randomly assign
about 950 of the 1,200 tested patients to the treatment protocol (assuming
that 80 percent of the tests will successfully allow classification of
patients as either EGFR-positive or EGFR-negative), and, after a minimum
of one to two years of follow-up, accrue data on disease-free and overall
patient survival rates as well as determine if markers are good predictive
and prognostic tools. It will also establish whether erlotinib provides a
meaningful benefit over the patients' initial, standard chemotherapy.

This trial is the outcome of a unique and innovative collaboration, formed
in 2006, called the Oncology Biomarkers Qualification Initiative (OBQI)
between NCI, the U.S. Food and Drug Administration (FDA), and the Centers
for Medicare and Medicaid Services. OBQI was designed to qualify
biomarkers for use in clinical trials and, ultimately, to speed better
agents to cancer patients.

"The MARVEL trial is unique and an important first because it is an
outgrowth of specific NCI initiatives designed to advance lung cancer
therapies and received broad input from the FDA, NCI cooperative groups,
the biomarker industry, and the pharmaceutical industry," said Alex A.
Adjei, M.D., Ph.D., senior vice president of Clinical Research at Roswell
Park Cancer Institute, Buffalo, N.Y., and chair of the study.

In addition to being chaired by the NCCTG, the trial represents a
collaborative effort of many of NCI's cooperative groups who perform lung
cancer research including the Cancer and Leukemia Group B (CALGB), the
Eastern Cooperative Oncology Group (ECOG), the Southwest Oncology Group
(SWOG), and the National Cancer Institute of Canada, Clinical Trials Group
(NCIC CTG), as well as industry partners. For more information on MARVEL,
please go to
http://www.clinicaltrials.gov/ct2/show/NCT00738881
Pemetrexed or Erlotinib as Second-Line Therapy in Treating Patients With
Advanced Non-Small Cell Lung Cancer

This study is currently recruiting participants.
Verified by National Cancer Institute (NCI), October 2008
Study Design: Treatment, Randomized
PURPOSE: This randomized phase III trial is studying pemetrexed to see how
well it works compared with erlotinib when given as second-line therapy in
treating patients with advanced non-small cell lung cancer.
Estimated Enrollment: 957
Study Start Date: October 2008
Estimated Primary Completion Date: May 2011 (Final data collection date
for primary outcome measure)

Arm I: Experimental
Patients receive oral erlotinib hydrochloride once daily on days 1-21.
Courses repeat every 21 days in the absence of disease progression or
unacceptable toxicity.
Drug: erlotinib hydrochloride
Given orally
Arm II: Experimental
Patients receive pemetrexed disodium IV over 10 minutes on day 1. Courses
repeat every 21 days in the absence of disease progression or unacceptable
toxicity.
Drug: pemetrexed disodium
Given IV

DISEASE CHARACTERISTICS:

*

Histologically confirmed non-small cell lung cancer (NSCLC), either
on initial diagnosis or at the time of disease recurrence/progression
o Mixed histology allowed if all components are consistent with
NSCLC
* Recurrent or progressive disease
*

Measurable disease, defined as at least one lesion whose longest
diameter can be accurately measured as ? 2.0 cm by conventional techniques
or as ? 1.0 cm by spiral CT scan
o Measurable disease must be outside of any previously
irradiated treatment field(s) unless there is disease progression or
recurrence within the irradiated field(s)
o

No nonmeasurable disease only, defined as any of the
following:
+ Bone lesions
+ Leptomeningeal disease
+ Ascites
+ Pleural/pericardial effusion
+ Inflammatory breast disease
+ Lymphangitis cutis/pulmonis
+ Abdominal masses not confirmed and followed by imaging
techniques
+ Cystic lesions
+ Single disease site in prior radiotherapy field
* Tumor tissue samples must be available and adequate for epidermal
growth factor receptor (EGFR) evaluation by FISH
*

Previously treated with only one cytotoxic chemotherapy regimen for
advanced disease
o Neoadjuvant/adjuvant cytotoxic chemotherapy administered < 12
months (from date chemotherapy was started) prior to study entry will be
counted as one prior treatment
o Neoadjuvant/adjuvant chemotherapy administered ? 12 months
prior to study entry and use of targeted agents (e.g., monoclonal
antibodies) will not be counted as one prior treatment
* No symptomatic serosal effusion (? grade 2 dyspnea as measured by
CTCAE v3.0) that is not amenable to drainage
*

No brain metastasis, unless the the following criteria are met:
o Brain metastasis is stable and has been previously treated
with either whole-brain radiotherapy or gamma-knife surgery
o More than 14 days since prior steroid treatment

PATIENT CHARACTERISTICS:

* ECOG performance status 0-2
* Life expectancy ? 12 weeks
* ANC ? 1,500/mm^3
* Platelet count ? 100,000/mm^3
* Hemoglobin ? 10 g/dL
* Total bilirubin ? 1.5 times upper limit of normal (ULN) OR direct
bilirubin normal
* AST and ALT ? 3 times ULN (? 5 times ULN if liver has tumor
involvement)
* PT/INR ? 1.5
* Creatinine clearance ? 45 mL/min
* Not pregnant or nursing
* Negative pregnancy test
* Fertile patients must use effective contraception
* Able to take folic acid, vitamin B_12 supplementation, and
dexamethasone
* No known HIV positivity
* No clinically significant infection
* No impaired gastrointestinal (GI) function, inability to swallow
pills in the absence of a feeding tube, or GI disease that may
significantly alter absorption of oral medications (e.g., ulcerative
disease, uncontrolled nausea and vomiting, malabsorption syndromes, or
bowel obstruction)
* No serious condition that, in the opinion of the investigator, would
preclude the patient's ability to complete the study therapy or increase
the risk for serious adverse events

[see the rest of the criteria]

Locations
United States, Florida
Mayo Clinic - Jacksonville Recruiting
Jacksonville, Florida, United States, 32224
Contact: Clinical Trials Office - All Mayo Clinic Locations
507-538-7623
United States, Minnesota
Mayo Clinic Cancer Center Recruiting
Rochester, Minnesota, United States, 55905
Contact: Clinical Trials Office - All Mayo Clinic Locations
507-538-7623


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