Study of NOV-002 in Combination With Chemotherapy to Treat Lung Cancer

Non Small Cell Lung Cancer Clinical Trial

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)

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00347412
• Other study ID #: NOV002-C301
• Status: Completed
• Phase: Phase 3
• Start date: November 2006
• Est. completion date: February 2010

Study information

• Verified date: July 2022
• Source: Cellectar Biosciences, Inc.
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Completed
• Enrollment: 903
• Est. completion date: February 2010
• Est. primary completion date: January 2010
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non Small Cell Lung Cancer

Intervention

Drug:
• Paclitaxel
Paclitaxel is dosed at 200 mg/m2, as a 3 hour infusion. All randomized patients will follow the established 21-day cycle of paclitaxel and carboplatin including the administration of pre-medications for these products per the package inserts. Paclitaxel and carboplatin cycles will be administered until documented disease progression or completion of 6 cycles of paclitaxel and carboplatin in the absence of response or unacceptable related toxicity, whichever comes first.
• NOV-002
Two 60 mg intravenous boli given 3 hours apart administered the day prior to the first administration of paclitaxel and carboplatin cycle one For each nominal 21-day paclitaxel and carboplatin cycle: 60 mg given intravenously on Day 1, given one hour prior to paclitaxel and carboplatin followed by 60 mg subcutaneously daily for the next 20 days. If there is a delay in chemotherapy cycles, the patient will continue with daily, subcutaneous administration of NOV-002 until the next cycle of chemotherapy begins Patients randomized to NOV-002 Group A, will receive NOV-002 until disease progression, unacceptable NOV-002 related toxicity, or discontinuation of paclitaxel and carboplatin, whichever comes first.
• Carboplatin
Carboplatin is dosed at an area under the curve (AUC) of 6 mg/mL/min using the Calvert equation for carboplatin dosing. All randomized patients will follow the established 21-day cycle of paclitaxel and carboplatin including the administration of pre-medications for these products per the package inserts. Paclitaxel and carboplatin cycles will be administered until documented disease progression or completion of 6 cycles of paclitaxel and carboplatin in the absence of response or unacceptable related toxicity, whichever comes first. The initial dose of chemotherapy for every patient in the trial is 200 mg/m2 of paclitaxel, as a 3 hour infusion, followed by carboplatin at an area under the curve (AUC) of 6 mg/mL/min using the Calvert equation for carboplatin dosing.

Locations

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

Sponsors (1)

Lead Sponsor	Collaborator
Cellectar Biosciences, Inc.

Countries where clinical trial is conducted

United States,  Canada,  Israel,  Italy,  Poland,  Romania,  Russian Federation,  Serbia,  Spain,  Switzerland,  Ukraine,  United Kingdom, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall survival during the length of the trial, length of the trial is approximately two years after last patient in		16 months
Secondary	Improved progression-free survival (PFS)		16 months
Secondary	Higher anti-tumor overall response rate (ORR)		16 months
Secondary	Less myelosuppression and improved recovery from chemotherapy-induced myelosuppression		16 months
Secondary	Immunomodulation as evidenced by changes in lymphocyte subsets		16 months