A Study of OGX-011/Gemcitabine/Platinum-Based Regimen in Stage IIIB/IV Non-Small Cell Lung Cancer (NSCLC)
This clinical study will help determine if giving OGX-011 (custirsen sodium) in combination with gemcitabine (GEM) and cisplatin (CIS) or carboplatin (CARB) is a safe and effective treatment for patients with lung cancer. This study will help to assess the safety and anti-tumor effect of OGX-011 when given to patients in combination with GEM and CIS/CARB.
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||A Phase 1-2 Study of Weekly OGX-011 Plus a Gemcitabine/Platinum-Based Regimen in Patients With Stage IIIB or IV Non Small Cell Lung Cancer|
- Objective Response Rate of OGX-011 in Combination With Gemcitabine/Platinum-based Regimen [ Time Frame: Based on assessments at baseline and after Cycles 2, 4, and 6. All subjects were followed for survival for a minimum of 3 years after the first dose of OGX-011 or until death. ] [ Designated as safety issue: No ]
Per RECIST Criteria V 1.0 and based on radiographic evaluations a subject was defined as having an objective response (OR) if the subject achieved either a confirmed partial response (PR) or confirmed complete response (CR).
The evaluations were conducted after every two cycles of treatment for a maximum of 6 cycles.
CR: disappearance of clinical/radiological evidence of tumor.
PR: >= 30% decrease in the sum of the longest diameter of target lesions.
SD: did not fulfill the criteria for CR or PR but not progressive disease.
- Progression-free Survival [ Time Frame: All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death. ] [ Designated as safety issue: No ]Progression-free survival (PFS) was defined as time from first treatment with OGX-011 to documented evidence of disease progression or date of death. For subjects without disease progression based on RECIST who initiated subsequent anti-cancer therapy, date of progression was defined as date of initiating new cancer treatment. PFS was censored as of the date of first OGX-011 dose for subjects who failed to return for assessments after screening. For subjects who were still alive and without progressive disease at the time of data cut-off, PFS was censored at date of last disease assessment.
- Overall Survival [ Time Frame: All subjects were followed for a minimum of 3 years after the first dose of OGX-011 or until death. ] [ Designated as safety issue: No ]Overall survival was defined as time from date of first treatment with OGX-011 to the date of death from any cause. Overall survival was censored at date of last contact for subjects who were still alive at end of study.
- Effect of OGX-011 on Serum Clusterin Levels [ Time Frame: Blood samples were collected at baseline and prior to infusion on Cycle 2 Day 1 and Cycle 3 Day 1 ] [ Designated as safety issue: No ]To measure the effect of OGX-011 on serum clusterin levels. The drug substance, OGX-011, is an antisense product designed to bind to clusterin mRNA, resulting in the inhibition of the production of human clusterin protein. Therefore, serum clusterin levels were expected to decrease.
- Cmax of OGX-011 [ Time Frame: Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2. ] [ Designated as safety issue: No ]Cmax is a plasma pharmacokinetic parameter that is defined as the maximum observed concentration of drug substance in plasma.
- t1/2 of OGX-011 [ Time Frame: Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2. ] [ Designated as safety issue: No ]Plasma half life of OGX-011
- AUC-0-last [ Time Frame: Blood samples were collected as follows. Cycle 1; Day 1: pre-dose, 2 h (EOI), 0.5 h, 1 hr, 1.5 h, 2.5 h, 4 h, 6.5 h and 23.5 h post end of OGX-011 infusion, Day 22: pre-dose Cycle 2. ] [ Designated as safety issue: No ]AUC-0-last is the area under the plasma concentration time curve from time 0 to the last last time point (23.5 hrs)
|Study Start Date:||November 2004|
|Study Completion Date:||March 2010|
|Primary Completion Date:||March 2010 (Final data collection date for primary outcome measure)|
Drug: custirsen sodium
OGX-011 is an experimental drug that has been shown to increase the effectiveness of commonly used cancer therapies such as chemotherapy, radiation and hormone therapy in several kinds of cancer types in animals. OGX-011 is being studied in the treatment of cancer patients in combination with chemotherapy. In humans, OGX-011 in combination with hormone therapy has been shown to decrease the tissue levels of a protein called clusterin, which can be overproduced in cancer cells. Clusterin has been found to block cell death and makes cells more resistant to cancer therapy. Gemcitabine (GEM), cisplatin (CIS) and carboplatin (CARB) have been approved by Health Canada and the Food and Drug Administration in the United States for the treatment of patients with lung cancer.
OGX-011 was administered as a 2-hr intravenous (IV) infusion on Days -7, -5, and -3 prior to Cycle 1, then weekly on Days 1, 8, 15 of each 21-day cycle; GEM was infused IV after OGX-011 on Days 1 and 8; either CIS or CARB was infused IV after GEM on Day 1 of each cycle. Six cycles of treatment were planned. Most patients received OGX-011 at 640 mg, but 3 patients received OGX-011 at 480 mg dose; OGX-011 dose groups were combined due to the small number of patients who received 480 mg.
|United States, California|
|University of Southern California Norris|
|Los Angeles, California, United States, 90033|
|LAC-USC Medical Center|
|Los Angeles, California, United States, 90033|
|United States, New York|
|New York Oncology Hematology|
|Albany, New York, United States, 12208|
|United States, Oregon|
|Oregon Health and Science University|
|Portland, Oregon, United States, 97239|
|United States, South Carolina|
|Cancer Centers of the Carolinas|
|Greenville, South Carolina, United States, 29605|
|United States, Texas|
|Mary Crowley Medical Research Center|
|Dallas, Texas, United States, 75246|
|Tom Baker Cancer Centre|
|Calgary, Alberta, Canada|
|Canada, British Columbia|
|BC Cancer Agency, Fraser Valley Centre|
|Surrey, British Columbia, Canada|
|BC Cancer Agency, Vancouver Center|
|Vancouver, British Columbia, Canada|
|Canada, Newfoundland and Labrador|
|Dr. H. Bliss Murphy Cancer Center|
|St. Johns, Newfoundland and Labrador, Canada|
|Royal Victoria Hospital of Barrie|
|Barrie, Ontario, Canada|
|London Regional Cancer Centre|
|London, Ontario, Canada|
|Ottawa, Ontario, Canada|
|Toronto Sunnybrook Regional Cancer Center|
|Toronto, Ontario, Canada|
|Ste-Foy, Quebec, Canada|
|Principal Investigator:||Janessa Laskin, M.D.||BCCA, Vancouver Clinic|