Lilly Launches Phase III 'GALES' Trial of ALIMTA(R) (Pemetrexed for Injection) in Small Cell Lung Cancer
20 October 2006 - 10:00PM
PR Newswire (US)
Global Trial - largest ever conducted in lung cancer subgroup -
currently enrolling patients INDIANAPOLIS, Oct. 20
/PRNewswire-FirstCall/ -- Eli Lilly and Company has launched a
major clinical trial evaluating ALIMTA (pemetrexed for injection)
in extensive-stage small cell lung cancer (SCLC), a devastating and
rapidly spreading form of lung cancer. This international trial,
expected to be the largest ever to be conducted in SCLC(1), will
assess the potential clinical benefit of pemetrexed in combination
with carboplatin, a commonly-used chemotherapeutic agent, in direct
comparison to the current leading treatment option of etoposide in
combination with carboplatin. The trial -- known as GALES for
Global Analysis of Pemetrexed in SCLC Extensive Stage -- is a Phase
III, global, multicenter, randomized, open-label study that will
enroll approximately 1,820 patients with extensive-stage SCLC. The
study's primary objective is to compare the overall survival after
treatment with pemetrexed plus carboplatin versus etoposide plus
carboplatin in previously untreated patients with extensive-stage
SCLC. The principal investigator of this study is Nick Thatcher,
M.D. of Christie Hospital NHS Trust in Manchester, United Kingdom.
SCLC accounts for between 15 and 20 percent of all lung cancers.(2)
Although SCLC is less common than the other main category of lung
cancer -- non-small cell lung cancer, SCLC tends to spread more
quickly and, as a result, people are typically diagnosed with
extensive disease and left without options such as surgery to
remove the cancer. "An innovative aspect of this study is that we
will employ the use of pharmacogenomic analysis to assess potential
biological characteristics relative to a patient's potential
response to chemotherapy," said Richard Gaynor, M.D., vice
president, cancer research and global oncology platform leader for
Eli Lilly and Company. Specifically, the study will use
pharmacogenomic analysis of patient- authorized tissue and blood
samples to determine if there are any biological characteristics
that would indicate a potentially higher clinical benefit from the
ALIMTA therapy for any patient sub-population groups.
Pharmacogenomics may one day help researchers find ways to "tailor"
chemotherapy to patients based on their biological indication to
benefit from specific treatments. The Phase II trial results for
the randomized study of pemetrexed plus carboplatin are featured in
the October 20, 2006 edition of the Journal of Clinical Oncology.
Preliminary results for the trial were first presented at the 2005
annual meeting of the American Society of Clinical Oncology in
Orlando, Florida.(3) In addition to comparing the overall survival
between the two patient groups, the study will also assess and
compare the patient groups based on the following secondary
objectives: * Overall survival in a subgroup of patients classified
as "sensitive" with respect to the results of a prospectively
defined set of biomarkers * Objective tumor response, or the
percentage of patients whose tumors shrink or disappear after
treatment * Time to event variables, including progression-free
survival, survival with Grade 4 toxicity, survival without Grade
3-4 toxicity, and time to worsening of health-related quality of
life More details on the study design and information on global
recruitment sites may be found at http://www.clinicaltrials.gov/,
http://www.lillytrials.com/, or by calling 1-877-CTLILLY
(1-877-285-4559). More About SCLC SCLC is sometimes called "oat
cell" cancer because small cell lung cancer cells resemble oat
grains. Patients with SCLC are staged according to a two- stage
system, being diagnosed as having either limited-stage disease or
extensive-stage disease. Approximately 65 - 70 percent of patients
with SCLC present with extensive-stage disease. Untreated patients
with extensive-stage SCLC have a median survival of approximately
five weeks and patients treated with chemotherapy have a median
survival of seven to 11 months. The current two-year survival rate
for patients with extensive SCLC is less than 10 percent with
current management options. Combination chemotherapy remains the
primary treatment option for patients with extensive-disease SCLC.
Currently, cisplatin or carboplatin in combination with etoposide
are the most commonly used regimens in SCLC.(4) About ALIMTA(R)
(pemetrexed for injection) Pemetrexed is a novel antifolate that
simultaneously blocks three separate enzyme targets important to
the formation of basic building blocks by which cancer cells grow
and divide. It is approved, in combination with cisplatin, for the
treatment of patients with malignant pleural mesothelioma whose
disease is unrectable or who are otherwise not candidates for
curative surgery. Important Safety Information Myelosuppression is
usually the dose-limiting toxicity with pemetrexed therapy.
Pemetrexed is contraindicated in patients who have a history of
severe hypersensitivity reaction to pemetrexed or to any other
ingredient used in the formulation. Warnings Patients must be
instructed to take folic acid and vitamin B12 with pemetrexed as a
prophylaxis to reduce treatment-related hematologic and GI
toxicities. Pemetrexed should not be administered to patients with
a creatinine clearance < 45 mL/min. One patient with severe
renal impairment (creatinine clearance 19 mL/min) who did not
receive folic acid and vitamin B12 died of drug-related toxicity
following administration of pemetrexed alone. Pemetrexed can
suppress bone marrow function, as manifested by neutropenia,
thrombocytopenia, and anemia (or pancytopenia). Pregnancy Category
D -- pemetrexed may cause fetal harm when administered to a
pregnant woman. Precautions Complete blood cell counts, including
platelet counts and periodic chemistry tests, should be performed
on all patients receiving pemetrexed. Patients should not begin a
new cycle of treatment unless the ANC is > 1500 cells/mm3 and
the platelet count is > 100,000 cells/mm3. Pretreatment with
dexamethasone or its equivalent has been reported to reduce the
incidence and severity of skin rash. The effect of third space
fluid, such as pleural effusion and ascites, on pemetrexed is
unknown. In patients with clinically significant third space fluid,
consideration should be given to draining the effusion prior to
pemetrexed administration. Caution should be used when
administering ibuprofen concurrently with pemetrexed to patients
with mild to moderate renal insufficiency (creatinine clearance
from 45 to 79 mL/min). Patients with mild to moderate renal
insufficiency should avoid taking NSAIDs with short elimination
half-lives for a period of 2 days before, the day of, and 2 days
following administration of pemetrexed. In the absence of data
regarding potential interaction between pemetrexed and NSAIDs with
longer half-lives, all patients taking these NSAIDs should
interrupt dosing for at least 5 days before, the day of, and 2 days
following pemetrexed administration. If concomitant administration
of an NSAID is necessary, patients should be monitored closely for
toxicity, especially myelosuppression, renal and gastrointestinal
toxicities. Concomitant administration of nephrotoxic drugs or
substances that are tubularly secreted could result in delayed
clearance of pemetrexed. It is recommended that nursing be
discontinued if the mother is being treated with pemetrexed.
Pemetrexed should be administered under the supervision of a
qualified physician experienced in the use of antineoplastic
agents. Dose adjustments may be necessary in patients with hepatic
insufficiency. Dosing and Modification Guidelines Dose adjustments
at the start of a subsequent cycle should be based on nadir
hematologic counts or maximum nonhematologic toxicity from the
preceding cycle of therapy. Modify or suspend therapy according to
the Dosage Reduction Guidelines in the full Prescribing
Information. Adverse Events The most common adverse events (grades
3/4) with pemetrexed in combination with cisplatin for the
treatment of patients with MPM were neutropenia (24%); leukopenia
(16%); anemia (6%); thrombocytopenia (5%); infection without
neutropenia (2%); fatigue (17%); thrombosis/embolism (6%); nausea
(12%); vomiting (11%); dyspnea (11%); and chest pain (9%). The most
common clinically relevant adverse events (all grades) were fatigue
(80%); thrombosis/embolism (7%); nausea (84%); vomiting (58%);
constipation (44%); anorexia (35%); stomatitis/pharyngitis (28%);
diarrhea (26%); dyspnea (66%); chest pain (40%); and rash (22%).
Copies of the package insert can be obtained via
http://www.alimta.com/ or calling 1-800-LILLY-RX (545-5979). Lilly
Oncology, a Division of Eli Lilly and Company For more than four
decades, Lilly Oncology has been collaborating with cancer
researchers to deliver innovative treatment choices and valuable
programs to patients and physicians. Inspired by courageous
patients living with cancer, Lilly Oncology is providing treatments
that are considered global standards of care and developing a broad
portfolio of novel targeted therapies to accelerate the pace and
progress of cancer care. To learn more about Lilly's commitment to
cancer, please visit http://www.lillyoncology.com/. About Eli Lilly
and Company Lilly, a leading innovation-driven corporation, is
developing a growing portfolio of first-in-class and best-in-class
pharmaceutical products by applying the latest research from its
own worldwide laboratories and from collaborations with eminent
scientific organizations. Headquartered in Indianapolis, Ind.,
Lilly provides answers -- through medicines and information -- for
some of the world's most urgent medical needs. Additional
information about Lilly is available at http://www.lilly.com/.
P-LLY (1) Investigators Thatcher N, Socinski M, Smit E et al ,
Randomized Phase III Trial of ALIMTA (Pemetrexed) and Carboplatin
versus Etoposide and Carboplatin in Extensive-Stage Small Cell Lung
Cancer; April 13, 2006. (2) Lung Cancer Alliance, "About Lung
Cancer," http://www.lungcanceralliance.org/facing/about.html
(October 6, 2006) (3) Socinski M, Weissman C, Hart L, et al. A
Randomized Phase II Trial of Pemetrexed/Cisplatin and
Pemetrexed/Carboplatin in Extensive Stage Small Cell Lung Cancer
(ES-SCLC), American Society of Clinical Oncology, Orlando, Florida,
May 15 - 17, 2005, Abstract #7165 (4) Investigators Thatcher N,
Socinski M, Smit E et al , Randomized Phase III Trial of ALIMTA
(Pemetrexed) and Carboplatin versus Etoposide and Carboplatin in
Extensive-Stage Small Cell Lung Cancer; April 13, 2006. This press
release contains forward-looking statements about the potential of
ALIMTA (pemetrexed) for the treatment of extensive-disease small
cell lung cancer and reflects Lilly's current beliefs. However, as
with any pharmaceutical product, there are substantial risks and
uncertainties in the process of development and commercialization.
There is no guarantee the product will receive regulatory approval
for a further indication, or that it will continue to be
commercially successful. For further discussion of these and other
risks and uncertainties, see Lilly's filings with the United States
Securities and Exchange Commission. Lilly undertakes no duty to
update forward-looking statements. ALIMTA(R) (pemetrexed, for
injection, Lilly) For more information, please visit:
http://www.lilly.com/news/media_kits/alimta.html (Logo:
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO )
http://www.newscom.com/cgi-bin/prnh/20031219/LLYLOGO DATASOURCE:
Eli Lilly and Company CONTACT: Gregory L. Clarke (Lilly), Email: ,
+1-317-276-5222 (office), +1-317-554-7119 (mobile)
Copyright