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Efficacy/Safety of Imprime PGG With Cetuximab & Paclitaxel/Carboplatin Therapy in Pts With Untreated Advanced Non-Small Cell Lung Cancer

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biothera
ClinicalTrials.gov Identifier:
NCT00874848
First received: April 1, 2009
Last updated: October 6, 2016
Last verified: October 2016
  Purpose
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.

Condition Intervention Phase
NSCLC
Biological: Imprime PGG Injection
Biological: Cetuximab
Drug: Paclitaxel
Drug: Carboplatin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
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

Resource links provided by NLM:


Further study details as provided by Biothera:

Primary Outcome Measures:
  • Objective Response Rate (ORR) in Each Study Arm Based on Independent Central Radiology Review [ Time Frame: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months ]

    Overall objective response rate was defined as the number of participants experiencing a best overall response of either complete response (CR) or partial response (PR) based on the modified RECIST v1.0 criteria.

    The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.



Secondary Outcome Measures:
  • Overall Survival (OS) in Each Study Arm Based on the Safety Population [ Time Frame: From the time of randomization to death, subject being lost to follow-up or study completion ]
    Overall survival (OS) was defined as the time from the date of randomization until the date of documented death of the subject due to any cause, including death due to relapses that were successfully retreated. Subjects who were lost to follow-up or who were still alive at the time of analysis were censored at the last contact dates.

  • Disease Control Rate (DCR) in Each Study Arm Based on Independent Central Radiology Review [ Time Frame: From first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months ]

    The disease control rate (DCR) was defined as the number of participants experiencing a best overall tumor response of either CR, PR or SD. For stable disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.

    The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.


  • Complete Response (CR), Partial Response (PR), and Stable Disease (SD) Rates in Each Study Arm Based on Independent Central Radiology Review [ Time Frame: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months ]

    The best observed overall response rates were defined as the number of participants experiencing a best overall response of either complete response (CR), partial response (PR) or stable disease (SD) based on the modified RECIST v1.0 criteria. For stable disease (SD), follow-up measurements must have met the SD criteria at least once after study entry at a minimum interval of 6 weeks.

    The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.


  • Duration of Objective Tumor Response in Each Study Arm Based on Independent Central Radiology Review [ Time Frame: From the first dose to disease progression or last tumor assessment before treatment discontinuation due to any reason, up to 15 months ]

    The duration of objective tumor response was measured from the time at which criteria are met for CR or PR (whichever status is recorded first) until the first date on which recurrence or progressive disease is objectively documented per modified RECIST v1.0. Subjects who did not progress as of the data cutoff date were censored at their last tumor assessment date.

    The analysis performed for this study utilized a modified RECIST v1.0 in which a confirmed response after the initial response assessment was not required by repeat assessment. With the use of centrally read, blinded radiological assessments performed by independent radiologists, and the use of randomization between study arms, the criterion requiring a 'confirmation' response was removed. All other RECIST v1.0 criteria remained unmodified and implemented as stated in the guidelines.


  • Duration of Time to Progression (TTP) in Each Study Arm Based on Independent Central Radiology Review [ Time Frame: From time of randomization to first date of documented progression, or last tumor assessment date, up to 15 months ]

    Time-to-progression (TTP) was defined as the time from the date of randomization to the first date of documented progressive disease. Progressive disease was identified by radiologic progressive disease according to modified RECIST v1.0, or in the case of the Investigator Radiologic Review, it may also be defined by clinical progression as determined by the investigator.

    If a subject received any further anti-cancer therapy without prior documentation of disease progression, the subject was censored at the date of last tumor assessment before starting anti-cancer treatment. Subjects who died on study from other causes (not related to study disease) and subjects who were lost to follow-up or who were alive without documented progressive disease as of the data cut-off date for analysis were censored at the last tumor assessment date.



Enrollment: 90
Study Start Date: August 2009
Study Completion Date: August 2015
Primary Completion Date: November 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Imprime PGG
Imprime PGG Injection + Cetuximab + Paclitaxel/Carboplatin
Biological: Imprime PGG Injection
4 mg/kg i.v. over 2 hrs, weekly, in three week cycles
Biological: Cetuximab
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
Other Name: Erbitux
Drug: Paclitaxel
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
Other Names:
  • Abraxane
  • Taxol
  • Onxol
  • Nov-Onxol
Drug: 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
Other Name: Paraplatin
Active Comparator: Control
Cetuximab + Paclitaxel/Carboplatin
Biological: Cetuximab
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
Other Name: Erbitux
Drug: Paclitaxel
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
Other Names:
  • Abraxane
  • Taxol
  • Onxol
  • Nov-Onxol
Drug: 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
Other Name: Paraplatin

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00874848

Locations
United States, Georgia
Medical College of Georgia
Augusta, Georgia, United States, 30912
United States, Indiana
Providence Medical Group
Terre Haute, Indiana, United States, 47802
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States, 55455
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States, 75201
Allison Cancer Center
Midland, Texas, United States, 79701
Germany
Helios Clinic Emil von Behring
Berlin, Germany
Municipal Clinic Frankfurt Hoescht
Frankfurt, Germany
Georg-August University Gottingen
Gottingen, Germany, 37075
University Clinical Heidelberg
Heidelberg, Germany
Clinic Minden
Minden, Germany
Techincal University of Munich
Munich, Germany
Clinic Nurnberg Nord
Nuremberg, Germany
Universitätsklinikum Ulm
Ulm, Germany, 89081
HELIOS Klinikum Wuppertal, Medizinische Klinik 1
Wuppertal, Germany, 42283
Sponsors and Collaborators
Biothera
Investigators
Principal Investigator: Folker Schneller, MD Technical University, Munich
  More Information

Responsible Party: Biothera
ClinicalTrials.gov Identifier: NCT00874848     History of Changes
Other Study ID Numbers: BT-CL-PGG-LCA0822 
Study First Received: April 1, 2009
Results First Received: July 15, 2016
Last Updated: October 6, 2016
Individual Participant Data  
Plan to Share IPD: No

Keywords provided by Biothera:
Imprime PGG
NSCLC
Cetuximab

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Carcinoma, Bronchogenic
Bronchial Neoplasms
Lung Neoplasms
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Neoplasms
Lung Diseases
Respiratory Tract Diseases
Paclitaxel
Albumin-Bound Paclitaxel
Carboplatin
Cetuximab
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action

ClinicalTrials.gov processed this record on February 23, 2017