The Phase 2 study described in this protocol will serve to evaluate the antitumor activity, safety and pharmacokinetic profile of Imprime PGG when combined with cetuximab and concomitant paclitaxel and carboplatin therapy in patients with previously untreated advanced NSCLC. Additionally, this study will provide guidance for the design of more definitive efficacy studies of Imprime PGG in NSCLC patients.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
90
4 mg/kg i.v. over 2 hrs, weekly, in three week cycles
initial loading dose of 400 mg/m\^2 over 120 min and subsequent doses at 250 mg/m\^2 over 60 min, weekly on Days 1, 8 and 15 of each 3-week treatment cycle
200 mg/m\^2 i.v. over 3 hr on Day 2 of each 3-week treatment cycle for the first 4 to 6 treatment cycles
Medical College of Georgia
Augusta, Georgia, United States
Providence Medical Group
Terre Haute, Indiana, United States
University of Minnesota
Minneapolis, Minnesota, United States
Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review
Overall objective response rate was defined as the number of participants experiencing a best overall response of either complete response (CR) or partial response (PR) based on the modified RECIST v1.0 criteria. The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.
Time frame: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
Overall Survival (OS) in Each Study Arm Based on the Safety Population
Overall survival (OS) was defined as the time from the date of randomization until the date of documented death of the subject due to any cause, including death due to relapses that were successfully retreated. Subjects who were lost to follow-up or who were still alive at the time of analysis were censored at the last contact dates.
Time frame: From the time of randomization to death, subject being lost to follow-up or study completion
Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review
The disease control rate (DCR) was defined as the number of participants experiencing a best overall tumor response of either CR, PR or SD. For stable disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks. The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.
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dose equal to an AUC of 6 mg/mL · min based on the Calvert formula; i.v. over 30 min on Day 2 of each 3-week treatment cycle for the first 4 to 6 treatment cycles
Mary Crowley Medical Research Center
Dallas, Texas, United States
Allison Cancer Center
Midland, Texas, United States
Helios Clinic Emil von Behring
Berlin, Germany
Municipal Clinic Frankfurt Hoescht
Frankfurt, Germany
Georg-August University Gottingen
Göttingen, Germany
University Clinical Heidelberg
Heidelberg, Germany
Clinic Minden
Minden, Germany
...and 4 more locations
Time frame: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review
The best observed overall response rates were defined as the number of participants experiencing a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) based on the modified RECIST v1.0 criteria. For stable disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks. The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.
Time frame: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review
The duration of objective tumor response was measured from the time at which criteria are met for CR or PR (whichever status is recorded first) until the first date on which recurrence or progressive disease is objectively documented per modified RECIST v1.0. Subjects who did not progress as of the data cutoff date were censored at their last tumor assessment date. The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.
Time frame: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review
Time-to-progression (TTP) was defined as the time from the date of randomization to the first date of documented progressive disease. Progressive disease was identified by radiologic progressive disease according to modified RECIST v1.0, or in the case of the Investigator Radiologic Review, it may also be defined by clinical progression as determined by the investigator. If a subject received any further anti-cancer therapy without prior documentation of disease progression, the subject was censored at the date of last tumor assessment before starting anti-cancer treatment. Subjects who died on study from other causes (not related to study disease) and subjects who were lost to follow-up or who were alive without documented progressive disease as of the data cut-off date for analysis were censored at the last tumor assessment date.
Time frame: From time of randomization to first date of documented progression, or last tumor assessment date, up to 15 months