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

NCT ID: NCT00874107

Last Updated: 2017-03-03

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 90 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2009-06-30
• Study Completion Date: 2016-05-31

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 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.

Conditions

Non-Small Cell Lung Cancer

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Imprime PGG + bevacizumab + paclitaxel/carboplatin

Group Type: EXPERIMENTAL

Imprime PGG® Injection

Intervention Type: BIOLOGICAL

4 mg/kg, i.v. over 2 hr, weekly until progression or discontinuation

Bevacizumab

Intervention Type: BIOLOGICAL

15 mg/kg, i.v., over 90 minutes, on Day 1 only of each 3-week treatment cycle

Paclitaxel

Intervention Type: DRUG

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

Intervention Type: DRUG

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

2

bevacizumab + paclitaxel/carboplatin

Group Type: OTHER

Bevacizumab

Intervention Type: BIOLOGICAL

15 mg/kg, i.v., over 90 minutes, on Day 1 only of each 3-week treatment cycle

Paclitaxel

Intervention Type: DRUG

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

Intervention Type: DRUG

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

Interventions

Imprime PGG® Injection

4 mg/kg, i.v. over 2 hr, weekly until progression or discontinuation

Intervention Type: BIOLOGICAL

Bevacizumab

15 mg/kg, i.v., over 90 minutes, on Day 1 only of each 3-week treatment cycle

Intervention Type: BIOLOGICAL

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.

Intervention Type: DRUG

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

Intervention Type: DRUG

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 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

HiberCell, Inc.

INDUSTRY

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Folker Schneller, MD

Role: PRINCIPAL_INVESTIGATOR

Klinikum rechts der Isar der Technischen Universitaet Muenchen

Locations

Highlands Oncology Group

Fayetteville, Arkansas, United States

Gabrail Cancer Center

Canton, Ohio, United States

University of Texas Health Science Center, San Antonio

San Antonio, Texas, United States

Kliniken der Stadt Köln gGmbH

Cologne, , Germany

Hospital Marth-Maria Halle Dolau

Halle, , Germany

Clinical Kassel GmbH

Kassel, , Germany

University of Mainz

Mainz, , Germany

University of Munich

Munich, , Germany

Pius-Hospital Oldenburg

Oldenburg, , Germany

Universitätsklinikum Ulm

Ulm, , Germany

Countries

United States; Germany

References

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.

Reference Type: BACKGROUND

PMID: 18281559 (View on PubMed)

Engel-Riedel W, Lowe J, Mattson P, Richard Trout J, Huhn RD, Gargano M, Patchen ML, Walsh R, Trinh MM, Dupuis M, Schneller F. A randomized, controlled trial evaluating the efficacy and safety of BTH1677 in combination with bevacizumab, carboplatin, and paclitaxel in first-line treatment of advanced non-small cell lung cancer. J Immunother Cancer. 2018 Feb 27;6(1):16. doi: 10.1186/s40425-018-0324-z.

Reference Type: DERIVED

PMID: 29486797 (View on PubMed)

Other Identifiers

BT-CL-PGG-LCA0821

Identifier Type: -

Identifier Source: org_study_id