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

NCT ID: NCT00347412

Last Updated: 2022-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 903 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-11-30
• Study Completion Date: 2010-02-28

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.

Conditions

Non Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group A: NOV-002 plus Chemotherapy

NOV-002 in combination with Paclitaxel and Carboplatin

Group Type: EXPERIMENTAL

Paclitaxel

Intervention Type: DRUG

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

Intervention Type: DRUG

• 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

Intervention Type: DRUG

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.

Group B: Chemotherapy Alone

Paclitaxel and Carboplatin

Group Type: ACTIVE_COMPARATOR

Paclitaxel

Intervention Type: DRUG

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.

Carboplatin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

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.

Intervention Type: DRUG

Other Intervention Names

Abraxane; Onxol; Taxol; Paraplatin

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Cellectar Biosciences, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Thomas Lynch, MD

Role: STUDY_CHAIR

Massachusetts General Hospital

Panos Fidias, MD

Role: STUDY_CHAIR

Massachusetts General Hospital

Locations

Northwest Alabama Cancer Center

Muscle Shoals, Alabama, United States

Sharp Memorial Hospital

San Diego, California, United States

University of Chicago Medical Center

Chicago, Illinois, United States

Northern Indiana Cancer Research Consortium

South Bend, Indiana, United States

St. Agnes Hospital

Baltimore, Maryland, United States

Massachusetts General Hospital

Boston, Massachusetts, United States

University of Minnesota Medical Center, Fairview

Minneapolis, Minnesota, United States

Park Nicollet Clinic - Cancer Center St. Louis Park

Saint Louis Park, Minnesota, United States

Dartmouth Hitchcock Medical Center

Lebanon, New Hampshire, United States

Cleveland Clinic Foundation Taussig Cancer Center

Cleveland, Ohio, United States

Thomas Jefferson University Hospital

Philadelphia, Pennsylvania, United States

South Texas Institute of Cancer

Corpus Christi, Texas, United States

William Osler Health Center

Brampton, Ontario, Canada

Humber River Regional Hospital

Weston, Ontario, Canada

Jewish General Hospital

Montreal, Quebec, Canada

Laval Hospital

Sainte-Foy, Quebec, Canada

Barzilai Medical Center

Ashkelon, , Israel

Lin Clinic

Haifa, , Israel

Meir Medical Center

Kfar Saba, , Israel

Institute of Oncology

Petah Tikva, , Israel

Sheba Medical Center

Ramat Gan, , Israel

Assaf Harofeh Hospital

Ẕerifin, , Israel

Azienda Ospedaliera Treviglio Caravaggio

Bergamo, , Italy

Azienda Ospedaliera Careggi

Florence, , Italy

Sondrio Hospital

Sondrio, , Italy

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

Warsaw, , Poland

S.C. Oncomed SRL

Timișoara, Timiș County, 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

Arkhangelsk Regional Clinical Oncology Center

Arkhangelsk, , Russia

Chelyabinsk Regional Oncology Center, Chemotherapy Department

Chelyabinsk, , Russia

Clinical Oncology Center, Chemotherapy Department

Kazan', , Russia

Omsk Regional Clinical Oncology Center

Omsk, , Russia

Orenburg Regional Clinical Oncology Center

Orenburg, , Russia

Stavropol Regional Clinical Oncology Center

Pyatigorsk, , Russia

Leningrad Regional Clinical Hospital, Department of Thoracic Surgery

Saint Petersburg, , Russia

City General Hospital #2, City Center of Intensive Pulmonology and Thoracic Surgery

Saint Petersburg, , Russia

St. Petersburg Pavlov State Medical University under the Federal Agency for Healthcare and Social Development

Saint Petersburg, , Russia

City Clinical Oncology Center, Thoracic Department

Saint Petersburg, , Russia

Oncology Center, Hematology Department

Sochi, , Russia

Stavropol Regional Clinical Oncology Center, Chemotherapy Department

Stavropol, , Russia

Tambov Regional Oncology Center, Chemotherapy Department

Tambov, , Russia

Kazan Oncology Center

Tatarstan, , Russia

Voronezh Regional Clinical Oncology Center

Voronezh, , Russia

Clinical Hospital Center Bezanijska kosa

Belgrade, , Serbia

Institute of Lung Diseases Sremka Kamenica

Kamenitz, , Serbia

Clinical Center Nis, Clinic for Lung Diseases "Knez Selo"

Niš, , Serbia

Hospital Clinic i Provincial de Barcelona

Barcelona, , Spain

Hospital Mutua de Terrassa

Terrassa, , Spain

Kantonales Spital Sursee-Wolhusen

Sursee, , Switzerland

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

Uzhhorod, , Ukraine

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 Kingdom

Countries

United States; Canada; Israel; Italy; Poland; Romania; Russia; Serbia; Spain; Switzerland; Ukraine; United Kingdom

Other Identifiers

NOV002-C301

Identifier Type: -

Identifier Source: org_study_id