Clinical trial NCT00347412: Study of NOV-002 in Combination With Chemotherapy to Treat Lung Cancer
Official title: Phase 3 Trial, Randomized, Open-Label, of NOV-002 in Combination With Paclitaxel and Carboplatin vs. Paclitaxel and Carboplatin Alone for the Treatment of Advanced Non-Small-Cell Lung Cancer (NSCLC)
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Non Small Cell Lung Cancer
Keywords: NSCLC
Stage IIIb
Stage IV
Non Small Cell Lung Cancer (NSCLC)
NSCLC Stage IIIb with malignant pleural/pericardial effusion
NSCLC Stage IV
Lead sponsor: Cellectar Biosciences, Inc.
Sponsor class: INDUSTRY
First posted: 2006-07-04
Enrollment: 903
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

Brief summary: 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 non-small cell lung cancer (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 in one United States 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, patients treated with NOV-002 with chemotherapy had a better survival rate than patients who did not receive NOV-002 with their chemotherapy.

Detailed description: NSCLC is a widespread disease with extremely high mortality and morbidity. Even the most widely accepted standard of care chemotherapy in advanced NSCLC, platinum-based doublets, are only palliative, providing marginal efficacy as measured by survival. In addition, such chemotherapy is accompanied by severe, sometimes life-threatening, toxicities which often limit its application. Thus, there is a clear need for new, more effective and safer therapies for advanced NSCLC. In Phase 2 trials, NOV-002 demonstrated a higher response rate and improved survival compared to chemotherapy alone in patients with advanced NSCLC, and was well-tolerated in this patient group. Thus, we are conducting a large Phase 3 trial of NOV-002 to better define its clinical profile and potential benefit in advanced NSCLC patients.

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.

Eligibility criteria: Inclusion Criteria:

* Diagnosis of Stage IIIb with malignant pleural or pericardial effusion or Stage IV (American Joint Committee on Cancer \[AJCC\]) NSCLC
* ECOG performance score of 0 or 1
* Adequate bone marrow, hepatic, and renal function
* New York Heart Association (NYHA) score 1-2
* Life expectancy of at least 12 weeks
* Women of child-bearing potential and men whose partners are of child-bearing potential must be willing to use an acceptable method of birth control during trial participation or are surgically sterile or women who are post-menopausal (defined as not having a menstrual cycle for greater than two years).
* The patient or patient's legal representative has the ability to understand the requirements of the trial, has provided written informed consent, and agrees to abide by the trial restrictions and to return for the required assessments.
* The patient must be able to self administer daily subcutaneous injections or his/her caregiver must be able to administer daily subcutaneous injections.

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 central nervous system (CNS) metastases
* Any systemic disease precluding chemotherapy
* Chronic use of systemic corticosteroids in pharmacological doses
* Known or history of HIV, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection
* 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 Food and Drug Administration (FDA) approved indication, within the 30 days prior to randomization
* Pregnant female or nursing mother

Primary outcomes:
measure: Overall survival during the length of the trial, length of the trial is approximately two years after last patient in
timeFrame: 16 months
Secondary outcomes:
measure: Improved progression-free survival (PFS)
timeFrame: 16 months
measure: Higher anti-tumor overall response rate (ORR)
timeFrame: 16 months
measure: Less myelosuppression and improved recovery from chemotherapy-induced myelosuppression
timeFrame: 16 months
measure: Immunomodulation as evidenced by changes in lymphocyte subsets
timeFrame: 16 months
Other outcomes:
Locations:
city: Muscle Shoals
country: United States
facility: Northwest Alabama Cancer Center
state: Alabama
city: San Diego
country: United States
facility: Sharp Memorial Hospital
state: California
city: Chicago
country: United States
facility: University of Chicago Medical Center
state: Illinois
city: South Bend
country: United States
facility: Northern Indiana Cancer Research Consortium
state: Indiana
city: Baltimore
country: United States
facility: St. Agnes Hospital
state: Maryland
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Minneapolis
country: United States
facility: University of Minnesota Medical Center, Fairview
state: Minnesota
city: Saint Louis Park
country: United States
facility: Park Nicollet Clinic - Cancer Center St. Louis Park
state: Minnesota
city: Lebanon
country: United States
facility: Dartmouth Hitchcock Medical Center
state: New Hampshire
city: Cleveland
country: United States
facility: Cleveland Clinic Foundation Taussig Cancer Center
state: Ohio
city: Philadelphia
country: United States
facility: Thomas Jefferson University Hospital
state: Pennsylvania
city: Corpus Christi
country: United States
facility: South Texas Institute of Cancer
state: Texas
city: Brampton
country: Canada
facility: William Osler Health Center
state: Ontario
city: Weston
country: Canada
facility: Humber River Regional Hospital
state: Ontario
city: Montreal
country: Canada
facility: Jewish General Hospital
state: Quebec
city: Sainte-Foy
country: Canada
facility: Laval Hospital
state: Quebec
city: Ashkelon
country: Israel
facility: Barzilai Medical Center
city: Haifa
country: Israel
facility: Lin Clinic
city: Kfar-Saba
country: Israel
facility: Meir Medical Center
city: Petach Tikva
country: Israel
facility: Institute of Oncology
city: Ramat Gan
country: Israel
facility: Sheba Medical Center
city: Zerifin
country: Israel
facility: Assaf Harofeh Hospital
city: Bergamo
country: Italy
facility: Azienda Ospedaliera Treviglio Caravaggio
city: Firenze
country: Italy
facility: Azienda Ospedaliera Careggi
city: Sondrio
country: Italy
facility: Sondrio Hospital
city: Bystra
country: Poland
facility: Oddzial Pulmonologiczny z Pododdzialem Chemioterapii
city: Gdansk
country: Poland
facility: Samodzielny Publiczny Szpital Kliniczny N°.1
city: Gdynia
country: Poland
facility: Oddzial Chemioterapii Pomorskie Centrum Onkologii,
city: Lodz
country: Poland
facility: Katedra Onkologii Akademii Medycznej w Lodzi
city: Olsztyn
country: Poland
facility: Oddzial Chemioterapii Zaklad Opieki Zdrowotnej MSWiA
city: Otwock
country: Poland
facility: Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy Oddzial III
city: Poznan
country: Poland
facility: Wielkopolskie Centrum Chorob
city: Prabuty
country: Poland
facility: Oddzial Gruzlicy I Chorob Pluc I P
city: Warsaw
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie w Warszawie
city: Warszawa
country: Poland
facility: Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
city: Timisoara
country: Romania
facility: S.C. Oncomed SRL
state: Timis County
city: Bucharest
country: Romania
facility: Institute of Oncology, Department of Medical Oncology II
city: Cluj-Napoca
country: Romania
facility: Institute of Oncology Cluj-Napoca
city: Cluj-Napoca
country: Romania
facility: Institute of Oncology, Cluj-Napoca
city: Craiova
country: Romania
facility: Craiova Emergency Clinical County Hospital
city: Arkhangelsk
country: Russian Federation
facility: Arkhangelsk Regional Clinical Oncology Center
city: Chelyabinsk
country: Russian Federation
facility: Chelyabinsk Regional Oncology Center, Chemotherapy Department
city: Kazan
country: Russian Federation
facility: Clinical Oncology Center, Chemotherapy Department
city: Omsk
country: Russian Federation
facility: Omsk Regional Clinical Oncology Center
city: Orenburg
country: Russian Federation
facility: Orenburg Regional Clinical Oncology Center
city: Pyatigorsk
country: Russian Federation
facility: Stavropol Regional Clinical Oncology Center
city: Sochi
country: Russian Federation
facility: Oncology Center, Hematology Department
city: St. Petersburg
country: Russian Federation
facility: Leningrad Regional Clinical Hospital, Department of Thoracic Surgery
city: St. Petersburg
country: Russian Federation
facility: City General Hospital #2, City Center of Intensive Pulmonology and Thoracic Surgery
city: St. Petersburg
country: Russian Federation
facility: St. Petersburg Pavlov State Medical University under the Federal Agency for Healthcare and Social Development
city: St. Petersburg
country: Russian Federation
facility: City Clinical Oncology Center, Thoracic Department
city: Stavropol
country: Russian Federation
facility: Stavropol Regional Clinical Oncology Center, Chemotherapy Department
city: Tambov
country: Russian Federation
facility: Tambov Regional Oncology Center, Chemotherapy Department
city: Tatarstan
country: Russian Federation
facility: Kazan Oncology Center
city: Voronezh
country: Russian Federation
facility: Voronezh Regional Clinical Oncology Center
city: Belgrade
country: Serbia
facility: Clinical Hospital Center Bezanijska kosa
city: Nis
country: Serbia
facility: Clinical Center Nis, Clinic for Lung Diseases "Knez Selo"
city: Sremska Kamenica
country: Serbia
facility: Institute of Lung Diseases Sremka Kamenica
city: Barcelona
country: Spain
facility: Hospital Clinic i Provincial de Barcelona
city: Terrassa
country: Spain
facility: Hospital Mutua de Terrassa
city: Sursee
country: Switzerland
facility: Kantonales Spital Sursee-Wolhusen
city: Cherkassy
country: Ukraine
facility: Cherkasy Regional Oncology Center
city: Chernihiv
country: Ukraine
facility: Public Treatment and Prophylaxis Institution: Chernihiv Regional Oncology Center
city: Dnipropetrovsk
country: Ukraine
facility: City General Hospital #4
city: Ivano-Frankivsk
country: Ukraine
facility: Regional Oncological Center
city: Kharkiv
country: Ukraine
facility: S.P. Grigoryev Institute of Medical Radiology
city: Kyiv
country: Ukraine
facility: Oncology Institute under the Ukrainian Academy of Medical Sciences
city: Simferopol
country: Ukraine
facility: Crimean Republican Clinical Oncology Center
city: Uzhorod
country: Ukraine
facility: Zakarpatsky Regional Oncological Clinical Center
city: Aberdeen
country: United Kingdom
facility: Anchor Unit, Aberdeen Royal Infirmary
state: Scotland
city: Dundee
country: United Kingdom
facility: Ninewells Hospital and Medical School Department of Cancer Medicine
state: Scotland
city: Guildford
country: United Kingdom
facility: St. Luke's Cancer Centre
state: Surrey
city: Nottingham
country: United Kingdom
facility: Oncology Research, Nottingham City Hospital
city: Poole
country: United Kingdom
facility: Dorset Cancer Centre, Poole Hospital
city: Somerset
country: United Kingdom
facility: Yeovil District Hospital NHS Foundation Trust, Higher Kingston
Study officials:
affiliation: Massachusetts General Hospital
name: Thomas Lynch, MD
role: STUDY_CHAIR
affiliation: Massachusetts General Hospital
name: Panos Fidias, MD
role: STUDY_CHAIR
References: