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

Non-Small Cell Lung Cancer Clinical Trial

Official title:

A Phase 2, Randomized, Efficacy and Safety Study of Imprime PGG® Injection in Combination With Bevacizumab 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: NCT00874107
• Other study ID #: BT-CL-PGG-LCA0821
• Status: Completed
• Phase: Phase 2
• First received: April 1, 2009
• Last updated: March 1, 2017
• Start date: June 2009
• Est. completion date: May 2016

Study information

• Verified date: March 2017
• Source: Biothera
• Contact: n/a
• Is FDA regulated: No
• 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 bevacizumab 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: May 2016
• Est. primary completion date: April 2016
• Accepts healthy volunteers: No
• Gender: All
• 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 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;

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:

1. ANC = 1,500/µL

2. PLT = 100,000/µL

3. HGB = 9 g/dL obtained within 1 week prior to the first dose of study medication;

9. Has adequate renal function as evidenced by:

1. Serum creatinine = 1.5 X the upper limit of normal (ULN) for the reference lab

2. 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:

1. Serum total bilirubin = 1.0 mg/dL

2. AST = 2.5X ULN for the reference lab (= 5X ULN for subjects with known hepatic metastases)

3. 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:

1. INR = 1.5

2. PTT = 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.

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:

1. Central nervous system (CNS) metastases

2. Uncontrolled hypertension (>150/100 mmHg) or hypertension that requires > two agents for adequate control

3. Peripheral neuropathy = grade 2 from any cause

4. Fever of >38.5° C within 3 days prior to screening or Day 1, initial dosing

5. 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:

1. Arterial or venous thromboembolic or hemorrhagic disorders including stroke, transient ischemic attack or cerebral infarction

2. Deep vein thrombosis within 1 year prior to screening

3. 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

4. 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 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:

1. Hemoptysis (= ½ tsp red blood)

2. 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.

Related Conditions & MeSH terms

• Carcinoma, Non-Small-Cell Lung
• Lung Neoplasms
• Non-Small Cell Lung Cancer

Intervention

Biological:
• Imprime PGG® Injection
4 mg/kg, i.v. over 2 hr, weekly until progression or discontinuation
• Bevacizumab
15 mg/kg, i.v., over 90 minutes, on Day 1 only 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
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	Hospital Marth-Maria Halle Dolau	Halle/Saale
Germany	Clinical Kassel GmbH	Kassel
Germany	Kliniken der Stadt Köln gGmbH	Köln
Germany	University of Mainz	Mainz
Germany	University of Munich	Munich
Germany	Pius-Hospital Oldenburg	Oldenburg
Germany	Universitätsklinikum Ulm	Ulm
United States	Gabrail Cancer Center	Canton	Ohio
United States	Highlands Oncology Group	Fayetteville	Arkansas
United States	University of Texas Health Science Center, San Antonio	San Antonio	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Biothera

Countries where clinical trial is conducted

United States,  Germany, 

References & Publications (1)

Salvador C, Li B, Hansen R, Cramer DE, Kong M, Yan J. Yeast-derived beta-glucan augments the therapeutic efficacy mediated by anti-vascular endothelial growth factor monoclonal antibody in human carcinoma xenograft models. Clin Cancer Res. 2008 Feb 15;14(4):1239-47. doi: 10.1158/1078-0432.CCR-07-1669. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine the objective response rate (ORR) in each study arm		Approximately 1.5 years
Secondary	To determine the disease control rate (DCR) in each study arm		Approximately 1.5 years
Secondary	To determine the complete response (CR), partial response (PR), and stable disease (SD) rates in each study arm		Approximately 1.5 years
Secondary	To determine the duration of objective tumor response in each study arm		Approximately 1.5 years
Secondary	To determine the duration of stable disease in each study arm		Approximately 1.5 years
Secondary	To determine the duration of time to progression (TTP) in each study arm		Approximately 1.5 years
Secondary	To assess the safety of the dosing regimen within each study arm		Approximately 1.5 years
Secondary	To determine the pharmacokinetic (PK) profile of Imprime PGG (in active treatment arm only)		Approximately 1.5 years