Study of NOV-002 in Combination With Chemotherapy to Treat Lung Cancer
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.
|Non Small Cell Lung Cancer||Drug: Paclitaxel and Carboplatin Drug: NOV-002 Injection in combination with Carboplatin vs. Paclitaxel and Carboplatin||Phase 3|
|Study Design:||Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Open Label
Primary Purpose: Treatment
|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)|
- Overall survival during the length of the trial, length of the trial is approximately two years after last patient in [ Time Frame: 16 months ]
- Improved progression-free survival (PFS) [ Time Frame: 16 months ]
- Higher anti-tumor overall response rate (ORR) [ Time Frame: 16 months ]
- Less myelosuppression and improved recovery from chemotherapy-induced myelosuppression [ Time Frame: 16 months ]
- Immunomodulation as evidenced by changes in lymphocyte subsets [ Time Frame: 16 months ]
|Study Start Date:||November 2006|
|Study Completion Date:||February 2010|
|Primary Completion Date:||January 2010 (Final data collection date for primary outcome measure)|
NOV-002 Injection in combination with Carboplatin and Paclitaxel
Drug: NOV-002 Injection in combination with Carboplatin vs. Paclitaxel and Carboplatin
NOV-002: (Group A only)
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.
Other Name: NOV-002 Injection
Active Comparator: B
Paclitaxel and Carboplatin Alone
Drug: Paclitaxel and Carboplatin
Paclitaxel and carboplatin: (All randomized patients)
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.
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.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00347412
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|Study Chair:||Thomas Lynch, MD||Massachusetts General Hospital|
|Study Chair:||Panos Fidias, MD||Massachusetts General Hospital|