Efficacy/Safety of Imprime PGG With Cetuximab & Paclitaxel/Carboplatin Therapy in Pts With Untreated Advanced Non-Small Cell Lung Cancer
Study Details
Study Description
Brief Summary
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.
| Condition or Disease | Intervention/Treatment | Phase |
|---|---|---|
|
Phase 2 |
Study Design
Arms and Interventions
| Arm | Intervention/Treatment |
|---|---|
| Experimental: Imprime PGG Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin |
Biological: Imprime PGG Injection
4 mg/kg i.v. over 2 hrs, weekly, in three week cycles
Biological: Cetuximab
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
Other Names:
Drug: Paclitaxel
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
Other Names:
Drug: Carboplatin
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
Other Names:
|
| Active Comparator: Control Cetuximab + Paclitaxel/Carboplatin |
Biological: Cetuximab
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
Other Names:
Drug: Paclitaxel
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
Other Names:
Drug: Carboplatin
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
Other Names:
|
Outcome Measures
Primary Outcome Measures
- Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review [From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months]
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.
Secondary Outcome Measures
- Overall Survival (OS) in Each Study Arm Based on the Safety Population [From the time of randomization to death, subject being lost to follow-up or study completion]
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.
- Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review [From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months]
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.
- Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review [From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months]
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.
- Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review [From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months]
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.
- Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review [From time of randomization to first date of documented progression, or last tumor assessment date, up to 15 months]
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.
Eligibility Criteria
Criteria
Inclusion Criteria:
-
Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC)
-
Is between the ages of 18 and 75 years old, inclusive
-
Has histologically or cytologically confirmed stage IIIB (malignant pericardial or pleural effusion) or stage IV non-small cell lung cancer
-
Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST
-
Has an ECOG performance status of 0 or 1
-
Has a life expectancy of > 3 months
-
Has adequate hematologic function as evidenced by:
-
ANC ≥ 1,500/μL
-
PLT ≥ 100,000/μL
-
HGB ≥ 9 g/dL obtained within 1 week prior to the first dose of study medication;
- Has adequate renal function as evidenced by:
-
Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) for the reference lab
-
Urine dipstick for proteinuria of < 1+ (i.e., either 0 or trace) within 2 weeks of Day 1 If urine dipstick is ≥ 1+, then urine protein excretion must be ≤ 500 mg over a 24 hour collection obtained within 1 week prior to the first dose of study medication;
- Has adequate hepatic function as evidenced by:
-
Serum total bilirubin ≤ 1.0 mg/dL
-
AST ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
-
ALT ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases) obtained within 1 week prior to the first dose of study medication;
- If a woman of childbearing potential or a fertile man (and his partners), must agree to use an effective form of contraception (hormonal contraceptive, double-barrier method or abstinence) during the study.
Exclusion Criteria:
-
Has received prior systemic chemotherapy at any time for lung cancer;
-
Has received previous radiation therapy to >30% of active bone marrow or any radiation therapy within 3 weeks of Day 1
-
Has a known hypersensitivity to baker's yeast, or has an active yeast infection
-
Has had previous exposure to Betafectin® or Imprime PGG
-
Has an active infection
-
Presents with any of the following medical diagnoses/conditions at the time of screening:
-
Central nervous system (CNS) metastases
-
Uncontrolled hypertension (>150/100 mmHg) or hypertension that requires > two agents for adequate control
-
Peripheral neuropathy ≥ grade 2 from any cause
-
Fever of >38.5° C within 3 days prior to screening or Day 1, initial dosing
-
Known HIV/AIDs, Hepatitis B, Hepatitis C, connective tissue or autoimmune disease, or other clinical diagnosis, ongoing or intercurrent illness that in the physician's opinion could interfere with participation
- Has a history of any of the following medical diagnoses/conditions:
-
Myocardial infarction or an unstable or uncontrolled disease or condition related to or impacting cardiac function (e.g., unstable angina, congestive heart failure) within the previous 6 months
-
Second malignancy within the previous 5 years, other than basal cell carcinoma, cervical intra-epithelial neoplasia or curatively treated prostate cancer with a PSA of <2.0 ng/mL
-
Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab
-
Has a know sensitivity to Cremophor EL
-
Has previously received treatment with cetuximab
-
If female, is pregnant or breast-feeding
-
Is receiving concurrent investigational therapy or has received investigational therapy within a period of 30 days prior to the first scheduled day of dosing (investigational therapy is defined as treatment for which there is currently no regulatory-authority-approved indication)
-
Has previously received an organ or progenitor/stem cell transplant.
Contacts and Locations
Locations
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Medical College of Georgia | Augusta | Georgia | United States | 30912 |
| 2 | Providence Medical Group | Terre Haute | Indiana | United States | 47802 |
| 3 | University of Minnesota | Minneapolis | Minnesota | United States | 55455 |
| 4 | Mary Crowley Medical Research Center | Dallas | Texas | United States | 75201 |
| 5 | Allison Cancer Center | Midland | Texas | United States | 79701 |
| 6 | Helios Clinic Emil von Behring | Berlin | Germany | ||
| 7 | Municipal Clinic Frankfurt Hoescht | Frankfurt | Germany | ||
| 8 | Georg-August University Gottingen | Gottingen | Germany | 37075 | |
| 9 | University Clinical Heidelberg | Heidelberg | Germany | ||
| 10 | Clinic Minden | Minden | Germany | ||
| 11 | Techincal University of Munich | Munich | Germany | ||
| 12 | Clinic Nurnberg Nord | Nuremberg | Germany | ||
| 13 | Universitätsklinikum Ulm | Ulm | Germany | 89081 | |
| 14 | HELIOS Klinikum Wuppertal, Medizinische Klinik 1 | Wuppertal | Germany | 42283 |
Sponsors and Collaborators
- HiberCell, Inc.
Investigators
- Principal Investigator: Folker Schneller, MD, Technical University, Munich
Study Documents (Full-Text)
None provided.More Information
Publications
None provided.- BT-CL-PGG-LCA0822
Study Results
Participant Flow
| Recruitment Details | A randomized, Simon 2-stage flexible design with 22 patients enrolled in stage 1 and 68 additional patients in stage 2, for a total of 90 subjects (60 in the Imprime PGG arm and 30 in the Control arm) enrolled competitively across US and German clinical sites. First subject enrolled: 17 Aug 2009 Last subject last visit: 15 Nov 2012 |
|---|---|
| Pre-assignment Detail | A total of 90 participants enrolled, 88 participants received at least one dose of study treatment, and 2 participants did not receive any study treatment. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG® infusion: 4 mg/kg i.v. over 2 to 4 hrs on Days 1, 8 and 15 of each 3-week treatment cycle; Cetuximab infusion: initial loading dose of 400 mg/m2 over 120 min and subsequent doses at 250 mg/m2 over 60 min, on Days 1, 8 and 15 of each 3-week treatment cycle; Paclitaxel infusion: 200 mg/m2 i.v. over 3 hr on Day 2 of each 3-week treatment cycle for the first 4 to 6 treatment cycles Carboplatin infusion: 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. Following the completion of at least the initial 4 treatment cycles (but no more than 6), participants experiencing stable disease, or a complete or partial response, were eligible to discontinue the chemotherapy treatment and continue dosing of Imprime PGG and cetuximab for a maximum of 18 treatment cycles without a treatment extension being authorized by the Sponsor. | Cetuximab infusion: initial loading dose of 400 mg/m2 over 120 min and subsequent doses at 250 mg/m2 over 60 min, on Days 1, 8 and 15 of each 3-week treatment cycle; Paclitaxel infusion: 200 mg/m2 i.v. over 3 hr on Day 2 of each 3-week treatment cycle for the first 4 to 6 treatment cycles Carboplatin infusion: 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. Following the completion of at least the initial 4 treatment cycles (but no more than 6), participants experiencing stable disease, or a complete or partial response, were eligible to discontinue the chemotherapy treatment and continue dosing of cetuximab for a maximum of 18 treatment cycles without a treatment extension being authorized by the Sponsor. |
| Period Title: Overall Study | ||
| STARTED | 59 | 29 |
| Discontinued | 59 | 28 |
| COMPLETED | 0 | 1 |
| NOT COMPLETED | 59 | 28 |
Baseline Characteristics
| Arm/Group Title | Imprime PGG Arm | Control Arm | Total |
|---|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin | Total of all reporting groups |
| Overall Participants | 59 | 29 | 88 |
| Age (Years) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [Years] |
59.3
(9.45)
|
62.4
(7.04)
|
60.45
(8.81)
|
| Sex: Female, Male (Count of Participants) | |||
| Female |
15
25.4%
|
12
41.4%
|
27
30.7%
|
| Male |
44
74.6%
|
17
58.6%
|
61
69.3%
|
| Race/Ethnicity, Customized (participants) [Number] | |||
| White |
56
94.9%
|
29
100%
|
85
96.6%
|
| Black |
2
3.4%
|
0
0%
|
2
2.3%
|
| Other |
1
1.7%
|
0
0%
|
1
1.1%
|
| Region of Enrollment (participants) [Number] | |||
| United States |
4
6.8%
|
2
6.9%
|
6
6.8%
|
| Germany |
55
93.2%
|
27
93.1%
|
82
93.2%
|
| ECOG (participants) [Number] | |||
| Score = 0 |
20
33.9%
|
10
34.5%
|
30
34.1%
|
| Score = 1 |
38
64.4%
|
18
62.1%
|
56
63.6%
|
| Missing |
1
1.7%
|
1
3.4%
|
2
2.3%
|
| Baseline Height (cm) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [cm] |
171.1
(7.51)
|
170.0
(8.90)
|
170.8
(7.96)
|
| Baseline Weight (kg) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg] |
76.2
(16.52)
|
72.8
(12.19)
|
75.0
(15.24)
|
| Baseline Body Mass Index (kg/m^2) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [kg/m^2] |
25.9
(4.95)
|
25.1
(3.00)
|
25.6
(4.40)
|
| Time from Initial Tumor Diagnosis (months) [Mean (Standard Deviation) ] | |||
| Mean (Standard Deviation) [months] |
0.9
(1.04)
|
0.9
(1.53)
|
0.9
(1.21)
|
| Prior Cancer Treatment (participants) [Number] | |||
| Radiotherapy |
0
0%
|
3
10.3%
|
3
3.4%
|
| Surgery |
23
39%
|
13
44.8%
|
36
40.9%
|
| Chemotherapy |
1
1.7%
|
1
3.4%
|
2
2.3%
|
Outcome Measures
| Title | Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary efficacy population comprised all randomized subjects who had no major violations of inclusion/exclusion or significant protocol violations & received any amount of cetuximab, paclitaxel or carboplatin therapy or Imprime PGG, & had an evaluable baseline scan & at least one evaluable post-baseline response based on modified RECIST v1.0. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin |
| Measure Participants | 41 | 26 |
| Number of participants with best response of CR |
0
0%
|
0
0%
|
| Number of participants with best response of PR |
15
25.4%
|
6
20.7%
|
Statistical Analysis 1
| Statistical Analysis Overview | Comparison Group Selection | Imprime PGG Arm, Control Arm |
|---|---|---|
| Comments | ||
| Type of Statistical Test | Superiority or Other | |
| Comments | ||
| Statistical Test of Hypothesis | p-Value | 0.2895 |
| Comments | ||
| Method | Fisher Exact | |
| Comments | ||
| Title | Overall Survival (OS) in Each Study Arm Based on the Safety Population |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The safety population comprised all randomized subjects who received any amount of Imprime PGG, cetuximab, paclitaxel or carboplatin. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin |
| Measure Participants | 59 | 29 |
| Median (95% Confidence Interval) [months] |
10.3
|
12.4
|
| Title | Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review |
|---|---|
| Description | 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. |
| Time Frame | From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary efficacy population comprised all randomized subjects who had no major violations of inclusion/exclusion or significant protocol violations & received any amount of cetuximab, paclitaxel or carboplatin therapy or Imprime PGG, & had an evaluable baseline scan & at least one evaluable post-baseline response based on modified RECIST v1.0. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin |
| Measure Participants | 41 | 26 |
| Number [participants] |
35
59.3%
|
21
72.4%
|
| Title | Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary efficacy population comprised all randomized subjects who had no major violations of inclusion/exclusion or significant protocol violations & received any amount of cetuximab, paclitaxel or carboplatin therapy or Imprime PGG, & had an evaluable baseline scan & at least one evaluable post-baseline response based on modified RECIST v1.0. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin |
| Measure Participants | 41 | 26 |
| Number of participants with best response of CR |
0
0%
|
0
0%
|
| Number of participants with best response of PR |
15
25.4%
|
6
20.7%
|
| Number of participants with best response of SD |
20
33.9%
|
15
51.7%
|
| Title | Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary efficacy population comprised all randomized subjects who had no major violations of inclusion/exclusion or significant protocol violations & received any amount of cetuximab, paclitaxel or carboplatin therapy or Imprime PGG, & had an evaluable baseline scan & at least one evaluable post-baseline response based on modified RECIST v1.0. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin |
| Measure Participants | 15 | 6 |
| Median (95% Confidence Interval) [months] |
4.4
|
4.1
|
| Title | Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review |
|---|---|
| Description | 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 |
Outcome Measure Data
| Analysis Population Description |
|---|
| The primary efficacy population comprised all randomized subjects who had no major violations of inclusion/exclusion or significant protocol violations & received any amount of cetuximab, paclitaxel or carboplatin therapy or Imprime PGG, & had an evaluable baseline scan & at least one evaluable post-baseline response based on modified RECIST v1.0. |
| Arm/Group Title | Imprime PGG Arm | Control Arm |
|---|---|---|
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin |
| Measure Participants | 41 | 26 |
| Median (95% Confidence Interval) [months] |
6.4
|
6.0
|
Adverse Events
| Time Frame | Serious adverse events (SAEs) and non-serious AEs were collected from the first dose of investigational product to the discontinuation of study plus 30 days after the last dose of study drug or until the subject began alternative therapy. | |||
|---|---|---|---|---|
| Adverse Event Reporting Description | ||||
| Arm/Group Title | Imprime PGG Arm | Control Arm | ||
| Arm/Group Description | Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin | Cetuximab + Paclitaxel/Carboplatin | ||
All Cause Mortality |
||||
| Imprime PGG Arm | Control Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | / (NaN) | / (NaN) | ||
Serious Adverse Events |
||||
| Imprime PGG Arm | Control Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 37/59 (62.7%) | 12/29 (41.4%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 1/59 (1.7%) | 2/29 (6.9%) | ||
| Anaemia | 1/59 (1.7%) | 1/29 (3.4%) | ||
| Febrile neutropenia | 1/59 (1.7%) | 0/29 (0%) | ||
| Haemorrhagic anaemia | 1/59 (1.7%) | 0/29 (0%) | ||
| Leukopenia | 1/59 (1.7%) | 0/29 (0%) | ||
| Thrombocytopenia | 0/59 (0%) | 1/29 (3.4%) | ||
| Cardiac disorders | ||||
| Acute myocardial infarction | 0/59 (0%) | 1/29 (3.4%) | ||
| Atrial fibrillation | 1/59 (1.7%) | 0/29 (0%) | ||
| Atrial flutter | 1/59 (1.7%) | 0/29 (0%) | ||
| Cardiac failure acute | 1/59 (1.7%) | 0/29 (0%) | ||
| Hypertrophic cardiomyopathy | 0/59 (0%) | 1/29 (3.4%) | ||
| Tachyarrhythmia | 1/59 (1.7%) | 0/29 (0%) | ||
| Tachycardia | 1/59 (1.7%) | 0/29 (0%) | ||
| Gastrointestinal disorders | ||||
| Diarrhoea | 0/59 (0%) | 2/29 (6.9%) | ||
| Abdominal pain | 1/59 (1.7%) | 0/29 (0%) | ||
| Gastric ulcer | 1/59 (1.7%) | 0/29 (0%) | ||
| Large intestine perforation | 1/59 (1.7%) | 0/29 (0%) | ||
| Pancreatitis | 1/59 (1.7%) | 0/29 (0%) | ||
| General disorders | ||||
| Asthenia | 0/59 (0%) | 1/29 (3.4%) | ||
| Chills | 1/59 (1.7%) | 0/29 (0%) | ||
| Death | 1/59 (1.7%) | 0/29 (0%) | ||
| Disease progression | 0/59 (0%) | 1/29 (3.4%) | ||
| General physical health deterioration | 1/59 (1.7%) | 0/29 (0%) | ||
| Infusion site extravasation | 1/59 (1.7%) | 0/29 (0%) | ||
| Mucosal inflammation | 0/59 (0%) | 1/29 (3.4%) | ||
| Hepatobiliary disorders | ||||
| Cholecystitis | 1/59 (1.7%) | 0/29 (0%) | ||
| Immune system disorders | ||||
| Anaphylactic shock | 1/59 (1.7%) | 0/29 (0%) | ||
| Hypersensitivity | 1/59 (1.7%) | 0/29 (0%) | ||
| Infections and infestations | ||||
| Erysipelas | 1/59 (1.7%) | 1/29 (3.4%) | ||
| Pneumonia | 1/59 (1.7%) | 1/29 (3.4%) | ||
| Anal abscess | 1/59 (1.7%) | 0/29 (0%) | ||
| Bronchitis | 1/59 (1.7%) | 0/29 (0%) | ||
| Diverticulitis | 1/59 (1.7%) | 0/29 (0%) | ||
| Neutropenic sepsis | 1/59 (1.7%) | 0/29 (0%) | ||
| Sepsis | 1/59 (1.7%) | 0/29 (0%) | ||
| Tonsillitis | 0/59 (0%) | 1/29 (3.4%) | ||
| Upper respiratory tract infection | 1/59 (1.7%) | 0/29 (0%) | ||
| Urinary tract infection | 0/59 (0%) | 1/29 (3.4%) | ||
| Urosepsis | 1/59 (1.7%) | 0/29 (0%) | ||
| Investigations | ||||
| Blood glucose increased | 1/59 (1.7%) | 0/29 (0%) | ||
| Metabolism and nutrition disorders | ||||
| Cachexia | 1/59 (1.7%) | 0/29 (0%) | ||
| Dehydration | 0/59 (0%) | 1/29 (3.4%) | ||
| Hypercalcaemia | 1/59 (1.7%) | 0/29 (0%) | ||
| Hypokalaemia | 0/59 (0%) | 1/29 (3.4%) | ||
| Hyponatraemia | 0/59 (0%) | 1/29 (3.4%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Bone pain | 1/59 (1.7%) | 0/29 (0%) | ||
| Osteoarthritis | 1/59 (1.7%) | 0/29 (0%) | ||
| Osteolysis | 1/59 (1.7%) | 0/29 (0%) | ||
| Nervous system disorders | ||||
| Epilepsy | 1/59 (1.7%) | 0/29 (0%) | ||
| Transient ischaemic attack | 1/59 (1.7%) | 0/29 (0%) | ||
| Psychiatric disorders | ||||
| Confusional state | 0/59 (0%) | 1/29 (3.4%) | ||
| Renal and urinary disorders | ||||
| Renal failure | 1/59 (1.7%) | 0/29 (0%) | ||
| Renal failure acute | 1/59 (1.7%) | 0/29 (0%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Pulmonary embolism | 5/59 (8.5%) | 2/29 (6.9%) | ||
| Pleural effusion | 6/59 (10.2%) | 0/29 (0%) | ||
| Dyspnoea | 2/59 (3.4%) | 1/29 (3.4%) | ||
| Haemoptysis | 2/59 (3.4%) | 0/29 (0%) | ||
| Bronchospasm | 1/59 (1.7%) | 0/29 (0%) | ||
| Pneumothorax | 1/59 (1.7%) | 0/29 (0%) | ||
| Pulmonary haemorrhage | 1/59 (1.7%) | 0/29 (0%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Dermatitis allergic | 1/59 (1.7%) | 0/29 (0%) | ||
| Rash | 0/59 (0%) | 1/29 (3.4%) | ||
| Vascular disorders | ||||
| Deep vein thrombosis | 0/59 (0%) | 1/29 (3.4%) | ||
| Hypotension | 1/59 (1.7%) | 0/29 (0%) | ||
| Vascular occulsion | 0/59 (0%) | 1/29 (3.4%) | ||
Other (Not Including Serious) Adverse Events |
||||
| Imprime PGG Arm | Control Arm | |||
| Affected / at Risk (%) | # Events | Affected / at Risk (%) | # Events | |
| Total | 59/59 (100%) | 29/29 (100%) | ||
| Blood and lymphatic system disorders | ||||
| Neutropenia | 22/59 (37.3%) | 14/29 (48.3%) | ||
| Leukopenia | 13/59 (22%) | 9/29 (31%) | ||
| Anaemia | 4/59 (6.8%) | 7/29 (24.1%) | ||
| Thrombocytopenia | 6/59 (10.2%) | 4/29 (13.8%) | ||
| Cardiac disorders | ||||
| Tachycardia | 2/59 (3.4%) | 2/29 (6.9%) | ||
| Gastrointestinal disorders | ||||
| Nausea | 25/59 (42.4%) | 12/29 (41.4%) | ||
| Diarrhoea | 24/59 (40.7%) | 9/29 (31%) | ||
| Constipation | 11/59 (18.6%) | 10/29 (34.5%) | ||
| Vomiting | 11/59 (18.6%) | 5/29 (17.2%) | ||
| Abdominal pain | 5/59 (8.5%) | 4/29 (13.8%) | ||
| Stomatitis | 4/59 (6.8%) | 4/29 (13.8%) | ||
| Dyspepsia | 4/59 (6.8%) | 2/29 (6.9%) | ||
| Dysphagia | 4/59 (6.8%) | 2/29 (6.9%) | ||
| Abdominal pain upper | 4/59 (6.8%) | 1/29 (3.4%) | ||
| Flatulence | 3/59 (5.1%) | 1/29 (3.4%) | ||
| Haemorrhoids | 1/59 (1.7%) | 2/29 (6.9%) | ||
| General disorders | ||||
| Fatigue | 30/59 (50.8%) | 17/29 (58.6%) | ||
| Mucosal inflammation | 13/59 (22%) | 6/29 (20.7%) | ||
| Chest pain | 10/59 (16.9%) | 5/29 (17.2%) | ||
| Chills | 8/59 (13.6%) | 4/29 (13.8%) | ||
| Pyrexia | 4/59 (6.8%) | 8/29 (27.6%) | ||
| Oedema peripheral | 5/59 (8.5%) | 5/29 (17.2%) | ||
| Asthenia | 3/59 (5.1%) | 3/29 (10.3%) | ||
| General physical health deterioration | 3/59 (5.1%) | 2/29 (6.9%) | ||
| Chest discomfort | 1/59 (1.7%) | 3/29 (10.3%) | ||
| Immune system disorders | ||||
| Hypersensitivity | 3/59 (5.1%) | 3/29 (10.3%) | ||
| Infections and infestations | ||||
| Nasopharyngitis | 6/59 (10.2%) | 3/29 (10.3%) | ||
| Paronychia | 6/59 (10.2%) | 2/29 (6.9%) | ||
| Bronchitis | 3/59 (5.1%) | 2/29 (6.9%) | ||
| Cystitis | 3/59 (5.1%) | 2/29 (6.9%) | ||
| Folliculitis | 5/59 (8.5%) | 0/29 (0%) | ||
| Infection | 3/59 (5.1%) | 0/29 (0%) | ||
| Pneumonia | 3/59 (5.1%) | 0/29 (0%) | ||
| Oral fungal infection | 0/59 (0%) | 2/29 (6.9%) | ||
| Rhinitis | 0/59 (0%) | 2/29 (6.9%) | ||
| Investigations | ||||
| Haemoglobin decreased | 5/59 (8.5%) | 0/29 (0%) | ||
| Amylase increased | 3/59 (5.1%) | 1/29 (3.4%) | ||
| Blood magnesium decreased | 4/59 (6.8%) | 0/29 (0%) | ||
| Blood phosphorus decreased | 2/59 (3.4%) | 2/29 (6.9%) | ||
| Weight decreased | 3/59 (5.1%) | 1/29 (3.4%) | ||
| White blood cell count decreased | 0/59 (0%) | 3/29 (10.3%) | ||
| Body temperature increased | 0/59 (0%) | 2/29 (6.9%) | ||
| Metabolism and nutrition disorders | ||||
| Decreased appetite | 13/59 (22%) | 7/29 (24.1%) | ||
| Hypokalaemia | 6/59 (10.2%) | 3/29 (10.3%) | ||
| Hypomagnesaemia | 6/59 (10.2%) | 2/29 (6.9%) | ||
| Hyperglycaemia | 4/59 (6.8%) | 1/29 (3.4%) | ||
| Hypocalcaemia | 2/59 (3.4%) | 2/29 (6.9%) | ||
| Dehydration | 3/59 (5.1%) | 0/29 (0%) | ||
| Musculoskeletal and connective tissue disorders | ||||
| Myalgia | 11/59 (18.6%) | 6/29 (20.7%) | ||
| Pain in extremity | 10/59 (16.9%) | 5/29 (17.2%) | ||
| Arthralgia | 6/59 (10.2%) | 4/29 (13.8%) | ||
| Bone pain | 5/59 (8.5%) | 5/29 (17.2%) | ||
| Back pain | 5/59 (8.5%) | 3/29 (10.3%) | ||
| Musculoskeletal pain | 5/59 (8.5%) | 1/29 (3.4%) | ||
| Muscle spasms | 4/59 (6.8%) | 1/29 (3.4%) | ||
| Pain in jaw | 0/59 (0%) | 2/29 (6.9%) | ||
| Neoplasms benign, malignant and unspecified (incl cysts and polyps) | ||||
| Tumour pain | 2/59 (3.4%) | 3/29 (10.3%) | ||
| Nervous system disorders | ||||
| Polyneuropathy | 16/59 (27.1%) | 9/29 (31%) | ||
| Paraesthesia | 7/59 (11.9%) | 9/29 (31%) | ||
| Dizziness | 8/59 (13.6%) | 6/29 (20.7%) | ||
| Headache | 7/59 (11.9%) | 4/29 (13.8%) | ||
| Dysgeusia | 5/59 (8.5%) | 5/29 (17.2%) | ||
| Neuropathy peripheral | 5/59 (8.5%) | 1/29 (3.4%) | ||
| Ageusia | 4/59 (6.8%) | 1/29 (3.4%) | ||
| Peripheral sensory neuropathy | 0/59 (0%) | 3/29 (10.3%) | ||
| Psychiatric disorders | ||||
| Insomnia | 7/59 (11.9%) | 5/29 (17.2%) | ||
| Sleep disorder | 3/59 (5.1%) | 1/29 (3.4%) | ||
| Renal and urinary disorders | ||||
| Renal pain | 1/59 (1.7%) | 2/29 (6.9%) | ||
| Respiratory, thoracic and mediastinal disorders | ||||
| Cough | 12/59 (20.3%) | 11/29 (37.9%) | ||
| Dyspnoea | 10/59 (16.9%) | 10/29 (34.5%) | ||
| Dysphonia | 6/59 (10.2%) | 6/29 (20.7%) | ||
| Epistaxis | 7/59 (11.9%) | 5/29 (17.2%) | ||
| Dyspnoea exertional | 5/59 (8.5%) | 2/29 (6.9%) | ||
| Oropharyngeal pain | 3/59 (5.1%) | 3/29 (10.3%) | ||
| Pleural effusion | 2/59 (3.4%) | 3/29 (10.3%) | ||
| Painful respiration | 0/59 (0%) | 2/29 (6.9%) | ||
| Skin and subcutaneous tissue disorders | ||||
| Rash | 28/59 (47.5%) | 19/29 (65.5%) | ||
| Alopecia | 22/59 (37.3%) | 13/29 (44.8%) | ||
| Dermatitis | 12/59 (20.3%) | 5/29 (17.2%) | ||
| Pruritus | 9/59 (15.3%) | 4/29 (13.8%) | ||
| Skin fissures | 11/59 (18.6%) | 2/29 (6.9%) | ||
| Dry skin | 6/59 (10.2%) | 3/29 (10.3%) | ||
| Night sweats | 3/59 (5.1%) | 1/29 (3.4%) | ||
| Nail disorder | 0/59 (0%) | 2/29 (6.9%) | ||
| Vascular disorders | ||||
| Hypotension | 4/59 (6.8%) | 1/29 (3.4%) | ||
| Thrombosis | 3/59 (5.1%) | 0/29 (0%) | ||
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
| Name/Title | Jamie Lowe, Vice President, Clinical Development |
|---|---|
| Organization | Biothera |
| Phone | 651-256-4653 |
| jlowe@biothera.com |
- BT-CL-PGG-LCA0822