NOV-002 for use in combination with first-line chemotherapy for the treatment of advanced non-small-cell lung cancer

http://www.fdanews.com/dailies/dpa/3_407/news/58728-1.html
NOVELOS' LUNG CANCER DRUG RECEIVES FAST-TRACK DESIGNATION

Novelos Therapeutics announced that the FDA has granted fast-track
designation to NOV-002 for use in combination with first-line chemotherapy
for the treatment of advanced non-small-cell lung cancer. The fast-track
designation is designed to facilitate the development and accelerate the
review process for new drugs that have the potential to address a serious
and unmet medical need for conditions.

Novelos now qualifies for rolling review of its NOV-002 new drug
application. Rolling review saves time by allowing the FDA to review of
application subsections as they become available, rather than delaying
review until all components are submitted together. In addition,
fast-track status results in more frequent meetings and communication with
FDA reviewers. Furthermore, the NOV-002 application will be more likely to
receive a priority review time of six months, rather than the standard 12
months.

http://www.clinicaltrials.gov/ct/show/NCT00347412?order=1
This study is currently recruiting patients.
Verified by Novelos Therapeutics July 2006
Sponsored by: Novelos Therapeutics
Information provided by: Novelos Therapeutics
ClinicalTrials.gov Identifier: NCT00347412
The purpose of this clinical trial is to find out whether or not the
combination of NOV-002 with chemotherapy (paclitaxel and carboplatin) is
better at improving overall survival time when compared to chemotherapy
alone in people with NSCLC

Earlier clinical trials in NSCLC showed that patients treated with NOV-002
in combination with chemotherapy had a better response (their tumors got
smaller, one US Phase 1/2 trial) than patients who received chemotherapy
alone and in two Phase 2 trials done in Russian patients at the end of one
year had a better survival than patients that did not receive NOV-002 with
their chemotherapy.
Condition Intervention Phase
Non Small Cell Lung Cancer (NSCLC)
NSCLC Stage IIIb With Malignant Pleural/Pericardial Effusion
NSCLC Stage IV
Drug: NOV-002
Phase III

Expected Total Enrollment: 840
The overall design of this Phase 3 trial reflects major elements of the
previous Russian and US clinical trials in advanced NSCLC - it is an open
label, randomized controlled trial comparing NOV-002 in combination with
first-line chemotherapy (paclitaxel + carboplatin) to first-line
chemotherapy alone. Furthermore, it is designed and powered to be a
pivotal, registrational trial, sufficient for approval. As its primary
efficacy endpoint, this Phase 3 trial aims to demonstrate that the
combination of NOV-002 with paclitaxel and carboplatin results in improved
overall survival when compared with paclitaxel and carboplatin alone. In
addition, several secondary efficacy endpoints will be assessed, including
progression free survival, tumor response rate and duration of response,
quality of life, myelosuppression and immunomodulation. Overall survival
was chosen as the primary endpoint of this trial in the context of FDA
(Draft) Guidance (?Clinical Trial Endpoints for the Approval of Cancer
Drugs and Biologics?, April 2005). This Guidance indicates that an
improvement in overall survival should be evaluated in randomized
controlled trials and is of unquestioned clinical benefit. It indicates
that the endpoint is precise and easy to measure, documented by the date
of death, and states that bias is not a factor in endpoint measurement,
and blinding is not essential. This Phase 3 randomized, controlled,
open-label trial thus conforms to this Guidance.

Exclusion Criteria:

Prior chemotherapy for advanced NSCLC or the patient has received prior
neoadjuvant or adjuvant chemotherapy for NSCLC in the year prior to the
date of randomization

Patients with CNS metastases

Any systemic disease precluding chemotherapy

Chronic use of systemic corticosteroids in pharmacological doses

Known or history of HIV, HBV or HCV

Contraindication to treatment with paclitaxel or carboplatin or any of the
components of NOV-002

Any known preexisting medical condition, including substance abuse, that
could interfere with the patient's participation in and completion of the
protocol

Have received any investigational drug, defined as a drug for which there
is no FDA approved indication, within the 30 days prior to randomization

Pregnant female or nursing mother

Location and Contact Information
Please refer to this study by ClinicalTrials.gov identifier NCT00347412

Paul Phillips 210-509-3559 PhillipsP@xxxxxxxxxx

Pennsylvania
Shannon Zimmerman, ICON, Pennsylvania, United States; Recruiting

Study chairs or principal investigators

Thomas Lynch, MD, Study Chair, Massachusetts General Hospital
Panos Fidias, MD, Study Chair, Massachusetts General Hospital

More Information
Study ID Numbers: NOV002-C301

http://meeting.jco.org/cgi/content/abstract/24/18_suppl/17021
NOV-002, a chemoprotectant/immunomodulator, added to first-line
carboplatin/paclitaxel in advanced non-small cell lung cancer (NSCLC): A
randomized Phase 1/2, open-label, controlled study
C. J. Pazoles and H. Gerstein

Novelos Therapeutics Inc, Newton, MA; Cancer Research of Long Island,
Great Neck, NY

17021

Background: NOV-002 is a proprietary formulation of oxidized glutathione
that modulates production of cytokines and hematopoietic growth factors. A
randomized, multi-site advanced NSCLC trial conducted in the Russian
Federation showed a one-year survival rate of 63% with NOV-002 + cytotoxic
chemotherapy compared to 17% with cytotoxic chemotherapy alone. Methods:
Forty-four chemotherapy-naïve, Stage IIIB/IV NSCLC patients (ECOG 0?2,
stratified by disease stage) were randomized to one of three groups for
six months of treatment: Groups A and B: NOV-002 in combination with
carboplatin and paclitaxel (C+P). For each nominal 21-day chemotherapy
cycle, these groups received 60 mg of NOV-002 i.v. daily for the first 4
days, then 60 mg i.m. (A) or s.c. (B) weekdays for the next 17 days. Group
C: C+P alone. Initial doses of C and P in all three groups were 225 mg/m2
and AUC 6, respectively. Initiation of repeat C+P cycles required an
absence of hematologic and other toxicities in excess of pre-defined
values. Primary study endpoints included tumor response (scans performed
at baseline and then every two months) and safety.

Results: An intent-to-treat analysis of the best overall objective tumor
response (WHO criteria), showed that 11 out of 16 (69%) Group B patients
demonstrated greater than 50% tumor shrinkage versus 5 out of 15 (33%) in
the control group (C) (p = 0.044, logistic regression stratified on
disease stage). Six out of 13 (46%) patients in Group A demonstrated an
objective response. 100% of NOV-002 treated patients in Group B and 85% in
Group A were able to complete four cycles of C+P compared to 50% of
control patients (Group C) (p = 0.004, chi square). NOV-002 was
well-tolerated in this patient population.

Conclusions: These data continue to suggest increased efficacy of NOV-002
plus cytotoxic chemotherapy compared to chemotherapy alone in advanced
NSCLC.

http://www.novelos.com/html/our_products/BAM_002.htm
NOV-002, the lead compound, is designed to act as a chemoprotectant



.