Efficacy/Safety of Imprime PGG With Cetuximab & Paclitaxel/Carboplatin Therapy in Pts With Untreated Advanced Non-Small Cell Lung Cancer
Condition: NSCLC
MeSH terms: Carcinoma, Non-Small-Cell Lung
Intervention: Imprime PGG Injection; Cetuximab; Paclitaxel; Carboplatin
Intervention description: 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; 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
Intervention MeSH terms: Paclitaxel; Carboplatin; Cetuximab; Albumin-Bound Paclitaxel
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 90.0
Sex: All
Minimum age: 18 Years
Maximum age: 75 Years
Healthy volunteers: No
Keywords: Imprime PGG; NSCLC; Cetuximab

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.
    

Eligibility criteria:

        Inclusion Criteria:

          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 measurable disease, defined as at least one tumor that fulfills the criteria for a
             target lesion according to RECIST

          5. Has an ECOG performance status of 0 or 1

          6. Has a life expectancy of > 3 months

          7. 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;

          8. 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;

          9. 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;

         10. 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:

          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:

               -  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

          7. 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

          8. Has a known hypersensitivity to cetuximab, murine proteins, or any component of
             cetuximab

          9. Has a know sensitivity to Cremophor EL

         10. Has previously received treatment with cetuximab

         11. If female, is pregnant or breast-feeding

         12. 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)

         13. Has previously received an organ or progenitor/stem cell transplant.