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

Purpose

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.

Condition	Intervention	Phase
Non Small Cell Lung Cancer	Drug: Paclitaxel and Carboplatin Drug: NOV-002 Injection in combination with Carboplatin vs. Paclitaxel and Carboplatin	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study 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)

Resource links provided by NLM:

MedlinePlus related topics: Cancer Lung Cancer

Drug Information available for: Glutathione disulfide Paclitaxel Carboplatin

U.S. FDA Resources

Further study details as provided by Novelos Therapeutics:

Primary Outcome Measures:

Overall survival during the length of the trial, length of the trial is approximately two years after last patient in [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

Improved progression-free survival (PFS) [ Time Frame: 16 months ] [ Designated as safety issue: No ]
Higher anti-tumor overall response rate (ORR) [ Time Frame: 16 months ] [ Designated as safety issue: No ]
Less myelosuppression and improved recovery from chemotherapy-induced myelosuppression [ Time Frame: 16 months ] [ Designated as safety issue: Yes ]
Immunomodulation as evidenced by changes in lymphocyte subsets [ Time Frame: 16 months ] [ Designated as safety issue: No ]

Estimated Enrollment:	880
Study Start Date:	November 2006
Study Completion Date:	February 2010
Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: A 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) Two 60mg 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: 60mg given intravenously on Day 1, given one hour prior to paclitaxel and carboplatin followed by 60mg 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. 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.

Arms

Assigned Interventions

Experimental: A

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)

Two 60mg 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:
- 60mg given intravenously on Day 1, given one hour prior to paclitaxel and carboplatin
- followed by 60mg 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.

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.

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

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00347412

Show 75 Study Locations

Sponsors and Collaborators

Novelos Therapeutics

Investigators

Study Chair:	Thomas Lynch, MD	Massachusetts General Hospital
Study Chair:	Panos Fidias, MD	Massachusetts General Hospital

More Information

No publications provided

Responsible Party:	Novelos Therapeutics
ClinicalTrials.gov Identifier:	NCT00347412 History of Changes
Other Study ID Numbers:	NOV002-C301
Study First Received:	June 29, 2006
Last Updated:	November 7, 2011
Health Authority:	United States: Food and Drug Administration United Kingdom: Medicines and Healthcare Products Regulatory Agency Swisterland: Swissmedic Poland: Ministry of Health Isreal: Ministry of Health Italy: Italian Medicines Agency Spain: Ministry of Health Canada: Health Canada Russia: Pharmacological Comitte, Ministry of Health

Keywords provided by Novelos Therapeutics:

NSCLC
Stage IIIb
Stage IV

Non Small Cell Lung Cancer (NSCLC)
NSCLC Stage IIIb with malignant pleural/pericardial effusion
NSCLC Stage IV

Additional relevant MeSH terms:

Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Carcinoma, Bronchogenic
Bronchial Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases

Carboplatin
Paclitaxel
Antineoplastic Agents
Therapeutic Uses
Pharmacologic Actions
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents, Phytogenic

ClinicalTrials.gov processed this record on May 16, 2013