Study of NOV-002 in Combination With Chemotherapy to Treat Lung Cancer
- Conditions
- Non Small Cell Lung Cancer
- Interventions
- Registration Number
- NCT00347412
- Lead Sponsor
- Cellectar Biosciences, Inc.
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 903
- 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.
- 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
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Group B: Chemotherapy Alone Paclitaxel Paclitaxel and Carboplatin Group A: NOV-002 plus Chemotherapy NOV-002 NOV-002 in combination with Paclitaxel and Carboplatin Group A: NOV-002 plus Chemotherapy Paclitaxel NOV-002 in combination with Paclitaxel and Carboplatin Group A: NOV-002 plus Chemotherapy Carboplatin NOV-002 in combination with Paclitaxel and Carboplatin Group B: Chemotherapy Alone Carboplatin Paclitaxel and Carboplatin
- Primary Outcome Measures
Name Time Method Overall survival during the length of the trial, length of the trial is approximately two years after last patient in 16 months
- Secondary Outcome Measures
Name Time Method Improved progression-free survival (PFS) 16 months Immunomodulation as evidenced by changes in lymphocyte subsets 16 months Less myelosuppression and improved recovery from chemotherapy-induced myelosuppression 16 months Higher anti-tumor overall response rate (ORR) 16 months
Trial Locations
- Locations (75)
Oddzial Chemioterapii Zaklad Opieki Zdrowotnej MSWiA
šµš±Olsztyn, Poland
Oddzial Gruzlicy I Chorob Pluc I P
šµš±Prabuty, Poland
Institute of Oncology, Department of Medical Oncology II
š·š“Bucharest, Romania
Kantonales Spital Sursee-Wolhusen
šØšSursee, Switzerland
Crimean Republican Clinical Oncology Center
šŗš¦Simferopol, Ukraine
City General Hospital #4
šŗš¦Dnipropetrovsk, Ukraine
Oncology Institute under the Ukrainian Academy of Medical Sciences
šŗš¦Kyiv, Ukraine
Katedra Onkologii Akademii Medycznej w Lodzi
šµš±Lodz, Poland
Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie
šµš±Warszawa, Poland
Dorset Cancer Centre, Poole Hospital
š¬š§Poole, United Kingdom
Northwest Alabama Cancer Center
šŗšøMuscle Shoals, Alabama, United States
Sharp Memorial Hospital
šŗšøSan Diego, California, United States
Thomas Jefferson University Hospital
šŗšøPhiladelphia, Pennsylvania, United States
William Osler Health Center
šØš¦Brampton, Ontario, Canada
University of Chicago Medical Center
šŗšøChicago, Illinois, United States
Northern Indiana Cancer Research Consortium
šŗšøSouth Bend, Indiana, United States
St. Agnes Hospital
šŗšøBaltimore, Maryland, United States
Massachusetts General Hospital
šŗšøBoston, Massachusetts, United States
University of Minnesota Medical Center, Fairview
šŗšøMinneapolis, Minnesota, United States
Park Nicollet Clinic - Cancer Center St. Louis Park
šŗšøSaint Louis Park, Minnesota, United States
Cleveland Clinic Foundation Taussig Cancer Center
šŗšøCleveland, Ohio, United States
South Texas Institute of Cancer
šŗšøCorpus Christi, Texas, United States
Humber River Regional Hospital
šØš¦Weston, Ontario, Canada
Laval Hospital
šØš¦Sainte-Foy, Quebec, Canada
Sheba Medical Center
š®š±Ramat Gan, Israel
Jewish General Hospital
šØš¦Montreal, Quebec, Canada
Barzilai Medical Center
š®š±Ashkelon, Israel
Lin Clinic
š®š±Haifa, Israel
Meir Medical Center
š®š±Kfar-Saba, Israel
Institute of Oncology
š®š±Petach Tikva, Israel
Azienda Ospedaliera Treviglio Caravaggio
š®š¹Bergamo, Italy
Assaf Harofeh Hospital
š®š±Zerifin, Israel
Sondrio Hospital
š®š¹Sondrio, Italy
Azienda Ospedaliera Careggi
š®š¹Firenze, Italy
Oddzial Pulmonologiczny z Pododdzialem Chemioterapii
šµš±Bystra, Poland
Samodzielny Publiczny Szpital Kliniczny NĀ°.1
šµš±Gdansk, Poland
Oddzial Chemioterapii Pomorskie Centrum Onkologii,
šµš±Gdynia, Poland
Mazowieckie Centrum Leczenia Chorob Pluc i Gruzlicy Oddzial III
šµš±Otwock, Poland
Wielkopolskie Centrum Chorob
šµš±Poznan, Poland
Centrum Onkologii - Instytut im. Marii Sklodowskiej-Curie w Warszawie
šµš±Warsaw, Poland
Institute of Oncology Cluj-Napoca
š·š“Cluj-Napoca, Romania
Institute of Oncology, Cluj-Napoca
š·š“Cluj-Napoca, Romania
S.C. Oncomed SRL
š·š“Timisoara, Timis County, Romania
Craiova Emergency Clinical County Hospital
š·š“Craiova, Romania
Arkhangelsk Regional Clinical Oncology Center
š·šŗArkhangelsk, Russian Federation
Chelyabinsk Regional Oncology Center, Chemotherapy Department
š·šŗChelyabinsk, Russian Federation
Oncology Center, Hematology Department
š·šŗSochi, Russian Federation
Clinical Oncology Center, Chemotherapy Department
š·šŗKazan, Russian Federation
Omsk Regional Clinical Oncology Center
š·šŗOmsk, Russian Federation
Orenburg Regional Clinical Oncology Center
š·šŗOrenburg, Russian Federation
Stavropol Regional Clinical Oncology Center
š·šŗPyatigorsk, Russian Federation
Leningrad Regional Clinical Hospital, Department of Thoracic Surgery
š·šŗSt. Petersburg, Russian Federation
Stavropol Regional Clinical Oncology Center, Chemotherapy Department
š·šŗStavropol, Russian Federation
St. Petersburg Pavlov State Medical University under the Federal Agency for Healthcare and Social Development
š·šŗSt. Petersburg, Russian Federation
City General Hospital #2, City Center of Intensive Pulmonology and Thoracic Surgery
š·šŗSt. Petersburg, Russian Federation
City Clinical Oncology Center, Thoracic Department
š·šŗSt. Petersburg, Russian Federation
Tambov Regional Oncology Center, Chemotherapy Department
š·šŗTambov, Russian Federation
Clinical Hospital Center Bezanijska kosa
š·šøBelgrade, Serbia
Kazan Oncology Center
š·šŗTatarstan, Russian Federation
Voronezh Regional Clinical Oncology Center
š·šŗVoronezh, Russian Federation
Hospital Mutua de Terrassa
šŖšøTerrassa, Spain
Clinical Center Nis, Clinic for Lung Diseases "Knez Selo"
š·šøNis, Serbia
Institute of Lung Diseases Sremka Kamenica
š·šøSremska Kamenica, Serbia
Hospital Clinic i Provincial de Barcelona
šŖšøBarcelona, Spain
Cherkasy Regional Oncology Center
šŗš¦Cherkassy, Ukraine
Public Treatment and Prophylaxis Institution: Chernihiv Regional Oncology Center
šŗš¦Chernihiv, Ukraine
Regional Oncological Center
šŗš¦Ivano-Frankivsk, Ukraine
S.P. Grigoryev Institute of Medical Radiology
šŗš¦Kharkiv, Ukraine
Anchor Unit, Aberdeen Royal Infirmary
š¬š§Aberdeen, Scotland, United Kingdom
Zakarpatsky Regional Oncological Clinical Center
šŗš¦Uzhorod, Ukraine
St. Luke's Cancer Centre
š¬š§Guildford, Surrey, United Kingdom
Oncology Research, Nottingham City Hospital
š¬š§Nottingham, United Kingdom
Ninewells Hospital and Medical School Department of Cancer Medicine
š¬š§Dundee, Scotland, United Kingdom
Yeovil District Hospital NHS Foundation Trust, Higher Kingston
š¬š§Somerset, United Kingdom
Dartmouth Hitchcock Medical Center
šŗšøLebanon, New Hampshire, United States