| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Patients with with Previously Untreated Advanced (Stage IIIB or IV) Non-Small Cell Lung Cancer |
|
| E.1.1.1 | Medical condition in easily understood language |
| Patients with with Previously Untreated Advanced (Stage IIIB or IV) Non-Small Cell Lung Cancer |
|
| E.1.1.2 | Therapeutic area | Diseases [C] - Cancer [C04] |
| MedDRA Classification |
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029522 |
| E.1.2 | Term | Non-small cell lung cancer stage IV |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10029521 |
| E.1.2 | Term | Non-small cell lung cancer stage IIIB |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.2 Medical condition or disease under investigation |
| E.1.2 | Version | 17.1 |
| E.1.2 | Level | PT |
| E.1.2 | Classification code | 10061873 |
| E.1.2 | Term | Non-small cell lung cancer |
| E.1.2 | System Organ Class | 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps) |
|
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
The objectives of this study are to assess the antitumor activity and safety of Imprime PGG® Injections (Imprime PGG) when used in combination with a monoclonal antibody and concomitant chemotherapy in non-small cell lung cancer (NSCLC).
The primary objective is:
• To determine the objective response rate (ORR) in each arm |
|
| E.2.2 | Secondary objectives of the trial |
• To determine the disease control rate (DCR) in each study arm
• To determine the overall survival (OS) in each study arm
• To determine the complete response (CR), partial response (PR), and stable disease (SD) rates in each study arm
• To determine the duration of objective tumor response in each study arm
• To determine the duration of stable disease in each study arm
• To determine the duration of time to progression (TTP) in each study arm
• To assess the safety of the dosing regimen in each study arm
• To determine the pharmacokinetic (PK) profile of Imprime PGG (in active treatment arm only)
|
|
| E.2.3 | Trial contains a sub-study | No |
| E.3 | Principal inclusion criteria |
Diagnosis and Main Criteria for Inclusion in the Study:
Inclusion Criteria
To be considered eligible to participate in the study, a subject must meet all of the inclusion criteria listed below.
The subject:
1. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review
Board/Ethics Committee (IRB/EC);
2. Is between the ages of 18 and 75 years old, inclusive;
3. Has histologically or cytologically confirmed stage IIIB (malignant pericardial or pleural effusion) or stage
IV non-small cell lung cancer;
4. Has non-squamous, non-small cell lung cancer
5. Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to
RECIST version 1.0;
6. Has an ECOG performance status of 0 or 1;
7. Has a life expectancy of > 3 months;
8. Has adequate hematologic function as evidenced by:
a. ANC ≥ 1,500/μL
b. PLT ≥ 100,000/μL
c. HGB ≥ 9 g/dL
obtained within 1 week prior to the first dose of study medication;
9. Has adequate renal function as evidenced by:
a. Serum creatinine ≤ 1.5 X the upper limit of normal (ULN) for the reference lab
b. 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;
10. Has adequate hepatic function as evidenced by:
a. Serum total bilirubin ≤ 1.0 mg/dL
b. AST ≤ 2.5X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
c. 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;
11. Has adequate coagulation function as evidenced by:
a. INR ≤ 1.5 X ULN for the reference lab
b. PTT ≤ 1.5 X ULN for the reference lab obtained within 1 week prior to the first dose of study medication;
12. 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. |
|
| E.4 | Principal exclusion criteria |
To be eligible for entry into the study, the subject must not meet any of the exclusion criteria listed below.
The subject:
1. Has received prior systemic chemotherapy at any time for lung cancer;
2. Has received previous radiation therapy to >30% of active bone marrow or any radiation therapy within 3
weeks of Day 1;
3. Has a known hypersensitivity to baker’s yeast, or has an active yeast infection;
4. Has had previous exposure to Betafectin® or Imprime PGG;
5. Has an active infection;
6. Presents with any of the following medical diagnoses/conditions at the time of screening:
a. Central nervous system (CNS) metastases
b. Uncontrolled hypertension (>150/100 mmHg) or hypertension that requires > two agents for
adequate control
c. Peripheral neuropathy ≥ grade 2 from any cause
d. Fever of >38.5° C within 3 days prior to screening or Day 1, initial dosing
e. 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
7. Has a history of any of the following medical diagnoses/conditions:
a. Arterial or venous thromboembolic or hemorrhagic disorders including stroke, transient ischemic
attack or cerebral infarction
b. Deep vein thrombosis within 1 year prior to screening
c. 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
d. Second malignancy within the previous 5 years, other than basal cell carcinoma, cervical intraepithelial
neoplasia or curatively treated prostate cancer with a PSA of <2.0 ng/mL
8. Has a known hypersensitivity to bevacizumab, murine proteins, or any component of bevacizumab;
9. Has a know sensitivity to polyethoxylated castor oil;
10. Has previously received treatment with bevacizumab;
11. Has had surgery within 4 weeks of Day 1 or needle or open biopsy within 1 week of Day 1;
12. Has a non-healing wound or gastric ulcer;
13. Has a non-healed bone fracture;
14. Is receiving systemic anti-coagulation therapy (e.g., dipyridalmole (Persantine®), ticlopidine (Ticlid®),
clopidogrel (Plavix®) and /or cilostazol (Pletal®);
15. Is receiving chronic daily treatment with aspirin (>100 mg/day) or other nonsteroidal anti-inflammatory
agents known to inhibit platelet function within 1 week of Day 1;
16. Presents with any of the following medical diagnoses/conditions at the time of screening:
a. Predominant squamous cell histology
17. Has a history of any of the following medical diagnoses/conditions:
a. Hemoptysis (≥ ½ tsp red blood)
b. Bleeding diathesis or coagulopathy
18. If female, is pregnant or breast-feeding;
19. 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);
20. Has previously received an organ or progenitor/stem cell transplant. |
|
| E.5 End points |
| E.5.1 | Primary end point(s) |
The primary endpoint of this study is:
• Objective response rate (ORR) in each study arm |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Subjects will initially be eligible to receive up to 18 cycles of treatment. With each treatment cycle lasting 3 weeks, the maximum duration of treatment will be 54 weeks, without a treatment extension being authorized by the Sponsor.
Patients who continue to experience a stable, partial or complete response (according to RECIST 1.0) following completion of the 18th treatment cycle, will be evaluated on a case-by-case basis by the investigator, the Medical Monitor and the study Sponsor to
determine eligibility for extending their treatment under this protocol.
|
|
| E.5.2 | Secondary end point(s) |
The secondary objectives of this study are:
o To determine the disease control rate (DCR) in each study arm
o To determine the overall survival (OS) in each study arm
o To determine the complete response (CR), partial response (PR), and stable disease (SD)
rates in each study arm
o To determine the duration of objective tumor response in each study arm
o To determine the duration of stable disease in each study arm
o To determine the duration of time to progression (TTP) in each study arm
o To assess the safety of the dosing regimen within each study arm
o To determine the pharmacokinetic (PK) profile of Imprime PGG (in active treatment arm only) |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Subjects will initially be eligible to receive up to 18 cycles of treatment. With each treatment cycle lasting 3 weeks, the maximum duration of treatment will be 54 weeks, without a treatment extension being authorized by the Sponsor.
Patients who continue to experience a stable, partial or complete response (according to RECIST 1.0) following completion of the 18th treatment cycle, will be evaluated on a case-by-case basis by the investigator, the Medical Monitor and the study Sponsor to determine eligibility for extending their treatment under this protocol.
|
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | Yes |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | Yes |
| E.7.3 | Therapeutic confirmatory (Phase III) | No |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | Yes |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | No |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | Yes |
| E.8.2.2 | Placebo | No |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 2 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 20 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | Yes |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.6.3 | If E.8.6.1 or E.8.6.2 are Yes, specify the regions in which trial sites are planned |
|
| E.8.7 | Trial has a data monitoring committee | Information not present in EudraCT |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 5 |
| E.8.9.1 | In the Member State concerned months | |
| E.8.9.1 | In the Member State concerned days | |
| E.8.9.2 | In all countries concerned by the trial years | 5 |
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