Efficacy/Safety of Imprime PGG® Injection With Cetuximab and Paclitaxel/Carboplatin Therapy in Patients With Untreated Advanced Non-Small Cell Lung Cancer (NSCLC)

NSCLC Clinical Trial

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00874848
• Other study ID #: BT-CL-PGG-LCA0822
• Status: Completed
• Phase: Phase 2
• First received: April 1, 2009
• Last updated: March 3, 2014
• Start date: August 2009
• Est. completion date: September 2013

Study information

• Verified date: March 2014
• Source: Biothera
• Contact: n/a
• Is FDA regulated: No
• Health authority: Germany: Federal Institute for Drugs and Medical Devices
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Est. completion date: September 2013
• Est. primary completion date: November 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

• 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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• NSCLC

Intervention

Biological:
• Imprime PGG® Injection
4 mg/kg i.v. over 2 hrs, weekly, in three week cycles
• Cetuximab
initial loading dose of 400 mg/m2 over 120 min and subsequent doses at 250 mg/m2 over 60 min, weekly on Days 1, 8 and 15 of each 3-week treatment cycle

Drug:
• Paclitaxel
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
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

Locations

Country	Name	City	State
Germany	Helios Clinic Emil von Behring	Berlin
Germany	Municipal Clinic Frankfurt Hoescht	Frankfurt
Germany	Georg-August University Gottingen	Gottingen
Germany	University Clinical Heidelberg	Heidelberg
Germany	Clinic Minden	Minden
Germany	Techincal University of Munich	Munich
Germany	Clinic Nurnberg Nord	Nuremberg
Germany	Universitätsklinikum Ulm	Ulm
Germany	HELIOS Klinikum Wuppertal, Medizinische Klinik 1	Wuppertal
United States	Medical College of Georgia	Augusta	Georgia
United States	Mary Crowley Medical Research Center	Dallas	Texas
United States	Allison Cancer Center	Midland	Texas
United States	University of Minnesota	Minneapolis	Minnesota
United States	Providence Medical Group	Terre Haute	Indiana

Sponsors (1)

Lead Sponsor	Collaborator
Biothera

Countries where clinical trial is conducted

United States,  Germany, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the objective response rate (ORR) in each study arm		Approximately 1.5 years	No
Secondary	To determine the disease control rate (DCR) in each study arm		Approximately 1.5 years	No
Secondary	To determine the complete response (CR), partial response (PR), and stable disease (SD) rates in each study arm		Approximately 1.5 years	No
Secondary	To determine the duration of objective tumor response in each study arm		Approximately 1.5 years	No
Secondary	To determine the duration of stable disease in each study arm		Approximately 1.5 years	No
Secondary	To determine the duration of time to progression (TTP) in each study arm		Approximately 1.5 years	No
Secondary	To assess the safety of the dosing regimen in each study arm		Approximately 1.5 years	Yes