Clinical trial NCT00874848: Efficacy/Safety of Imprime PGG With Cetuximab & Paclitaxel/Carboplatin Therapy in Pts With Untreated Advanced Non-Small Cell Lung Cancer
Official title: Efficacy and Safety Study of Imprime PGG® Injection in Combination With Cetuximab and Concomitant Paclitaxel and Carboplatin Therapy in Patients With Previously Untreated Advanced (Stage IIIB or IV) Non-Small Cell Lung Cancer
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: NSCLC
Keywords: Imprime PGG
NSCLC
Cetuximab
Lead sponsor: HiberCell, Inc.
Sponsor class: INDUSTRY
First posted: 2009-04-03
Enrollment: 90
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


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.

Primary outcomes:
measure: Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review
timeFrame: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
Secondary outcomes:
measure: Overall Survival (OS) in Each Study Arm Based on the Safety Population
timeFrame: From the time of randomization to death, subject being lost to follow-up or study completion
measure: Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review
timeFrame: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
measure: Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review
timeFrame: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
measure: Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review
timeFrame: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months
measure: Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review
timeFrame: From time of randomization to first date of documented progression, or last tumor assessment date, up to 15 months
Other outcomes:
Locations:
city: Augusta
country: United States
facility: Medical College of Georgia
state: Georgia
city: Terre Haute
country: United States
facility: Providence Medical Group
state: Indiana
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Dallas
country: United States
facility: Mary Crowley Medical Research Center
state: Texas
city: Midland
country: United States
facility: Allison Cancer Center
state: Texas
city: Berlin
country: Germany
facility: Helios Clinic Emil von Behring
city: Frankfurt
country: Germany
facility: Municipal Clinic Frankfurt Hoescht
city: Gottingen
country: Germany
facility: Georg-August University Gottingen
city: Heidelberg
country: Germany
facility: University Clinical Heidelberg
city: Minden
country: Germany
facility: Clinic Minden
city: Munich
country: Germany
facility: Techincal University of Munich
city: Nuremberg
country: Germany
facility: Clinic Nurnberg Nord
city: Ulm
country: Germany
facility: Universitätsklinikum Ulm
city: Wuppertal
country: Germany
facility: HELIOS Klinikum Wuppertal, Medizinische Klinik 1
Study officials:
affiliation: Technical University, Munich
name: Folker Schneller, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Thomas M, Sadjadian P, Kollmeier J, Lowe J, Mattson P, Trout JR, Gargano M, Patchen ML, Walsh R, Beliveau M, Marier JF, Bose N, Gorden K, Schneller F 3rd. A randomized, open-label, multicenter, phase II study evaluating the efficacy and safety of BTH1677 (1,3-1,6 beta glucan; Imprime PGG) in combination with cetuximab and chemotherapy in patients with advanced non-small cell lung cancer. Invest New Drugs. 2017 Jun;35(3):345-358. doi: 10.1007/s10637-017-0450-3. Epub 2017 Mar 16.