Study of Imprime PGG® in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer
- Conditions
- Colorectal Cancer
- Interventions
- Biological: Imprime PGG + cetuximab
- Registration Number
- NCT01309126
- Lead Sponsor
- HiberCell, Inc.
- Brief Summary
Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified subjects, who have KRAS wild type (WT) colorectal cancer will be randomized in a 2:1 ratio to treatment with either Imprime PGG and cetuximab or cetuximab alone. Subjects will be dosed until progression or discontinuation for some other reason. Efficacy will be assessed via Response Evaluation Criteria in Early Tumors 1.1 (RECIST 1.1); computed tomography (CT) scans will be conducted every 6 weeks. Safety, pharmacokinetics (PK), quality of life, and biomarker parameters will also be assessed.
- Detailed Description
Study BT-CL-PGG-CRC1031 is a Phase 3, open-label, randomized, multi-center study. Qualified subjects, who have KRAS WT colorectal cancer will be randomized in a 2:1 ratio to either:
Arm 1: Imprime PGG and cetuximab or Arm 2: Cetuximab
Approximately 795 subjects will be randomized into the study. Dosing will occur in 6-week cycles. Imprime PGG will be dosed at 4 mg/kg and will be administered weekly in each cycle (Weeks 1-6/Days 1, 8, 15, 22, 29, and 36) preceding the administration of cetuximab (Arm 1 only). The initial cetuximab dose (both arms) will be 400 mg/m2 on Cycle 1/Day 1 and subsequent doses will be 250 mg/m2 administered weekly in each cycle (Weeks 1-6/Days 1, 8, 15, 22, 29, and 36).
Subjects will be dosed until progressive disease (PD) per RECIST 1.1 or discontinuation of study drug for other reasons; e.g., safety. Following completion of the treatment period of the study, subjects will be monitored for survival until death or loss to follow-up. Tumor measurements and determination of tumor responses will be evaluated according to RECIST 1.1. Safety, PK, quality of life, and biomarker parameters will also be assessed.
Recruitment & Eligibility
- Status
- TERMINATED
- Sex
- All
- Target Recruitment
- 217
-
Is >18 years old;
-
Has recurrent or metastatic carcinoma of the colon or rectum with documented histological or cytological confirmation;
-
Must be KRAS WT;
-
Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1;
-
Has never received cetuximab or panitumumab, and has not received any treatment for colorectal cancer within 30 days prior to the first dose of study treatment under this protocol;
-
Has an Eastern Cooperative Oncology Group (ECOG) score of 0-1, with a life expectancy of >3 months;
-
Has received at least 2 prior chemotherapeutic regimens for colorectal cancer;
-
Has adequate bone marrow reserve as evidenced by:
- Absolute neutrophil count ≥1,500/μL
- Platelets ≥100,000/μL;
-
Has adequate renal function as evidenced by serum creatinine ≤2.5 × the upper limit of normal (ULN) for the reference lab;
-
Has adequate hepatic function as evidenced by:
- Aspartate aminotransferase ≤3 × ULN for the reference lab (≤5 × ULN for subjects with known hepatic metastases)
- Alanine aminotransferase ≤3 × ULN for the reference lab (≤5 × ULN for subjects with known hepatic metastases)
- Bilirubin <1.5 mg/dL or direct bilirubin <1.0 mg/dL
- Serum Albumin >3.0 gm/dL
-
Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Independent Ethics Committee (IRB/IEC); and
-
If the subject is a woman of childbearing potential or a fertile man, he/she must agree to use an effective form of contraception during the study and for 60 days following the last dose of study drug (an effective form of contraception is abstinence, a hormonal contraceptive, or a double-barrier method).
- Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
- Has a known hypersensitivity to baker's yeast or has an active yeast infection;
- Has had previous exposure to Betafectin® or Imprime PGG;
- Has an active, uncontrolled infection;
- Has known untreated or symptomatic brain metastases;
- Had a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia or treated prostate cancer with a prostate-specific antigen (PSA) of <2.0 ng/mL;
- Has known human immunodeficiency virus or acquired immune deficiency syndrome, hepatitis B, hepatitis C, connective tissue disease, or other clinical diagnosis, ongoing or intercurrent illness that in the Investigators opinion should preclude the subject from participation;
- If female, is pregnant or breast-feeding;
- Is receiving concurrent standard and/or investigational anti-cancer therapy or has received such 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); or
- Has previously received an organ or progenitor/stem cell transplant.
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description Arm 1: Imprime PGG + cetuximab Imprime PGG + cetuximab Biological/Vaccine + Drug Arm 2: cetuximab Cetuximab Drug
- Primary Outcome Measures
Name Time Method Overall Survival (OS) 18 months
- Secondary Outcome Measures
Name Time Method Progression Free Survival (PFS) 18 months Rate of complete response (CR) 18 months Rate of partial response (PR) 18 months Rate of overall response (CR + PR) 18 months Safety and tolerability of the dosing regimen as measured by the incidence and severity of adverse events observed in study participants 18 months Sparse pharmacokinetic profile of Imprime PGG will be determined to expand current Imprime PGG PK data 18 months Samples for sparse PK will be taken at specified times on Cycle 1/Day 1 in the first 30 available subjects randomized to Arm 1 (Subjects 1-30). Samples will be collected, at multiple times, in the next 60 subjects randomized to Arm 1 who reach Cycle 2/Day 1 of dosing (subjects 31-90). Additionally, any subject after the first 90 subjects (subjects 91-795) who have a screening/baseline calculated creatinine clearance (based on age, weight and serum creatinine) of \<60 mL/minute will have sparse PK samples collected.
Change in Quality of Life 18 months
Trial Locations
- Locations (53)
Ellis Fischel Cancer Center at University of Missouri- Columbia
🇺🇸Columbia, Missouri, United States
Hematology and Oncology Associates of Central NY
🇺🇸East Syracuse, New York, United States
Texas Oncology - Baylor Charles A. Sammons Cancer Center
🇺🇸Dallas, Texas, United States
Medical and Surgical Specialists
🇺🇸Galesburg, Illinois, United States
Kenmar Research Institute
🇺🇸Los Angeles, California, United States
Massachusetts General Hospital
🇺🇸Boston, Massachusetts, United States
Dana Farber Cancer Institute
🇺🇸Boston, Massachusetts, United States
MD Anderson Cancer Center
🇺🇸Orlando, Florida, United States
University of Minnesota
🇺🇸Minneapolis, Minnesota, United States
Highlands Oncology Group
🇺🇸Bentonville, Arkansas, United States
Providence St. Joseph Medical Center
🇺🇸Burbank, California, United States
Illinois Cancer Specialists
🇺🇸Niles, Illinois, United States
University of Louisville/James Brown Cancer Center
🇺🇸Louisville, Kentucky, United States
Ochsner Clinic Foundation
🇺🇸New Orleans, Louisiana, United States
Providence Portland Medical Center
🇺🇸Portland, Oregon, United States
Tennessee Cancer Specialists
🇺🇸Knoxville, Tennessee, United States
The Jones Clinic
🇺🇸Germantown, Tennessee, United States
Texas Oncology-Amarillo
🇺🇸Amarillo, Texas, United States
Texas Oncology - Dallas Presbyterian Hospital
🇺🇸Dallas, Texas, United States
Texas Oncology - Fort Worth
🇺🇸Fort Worth, Texas, United States
Texas Oncology - Lewisville
🇺🇸Lewisville, Texas, United States
Texas Oncology-Seton Williamson
🇺🇸Round Rock, Texas, United States
Northern Utah Associates
🇺🇸Ogden, Utah, United States
Texas Oncology - Tyler
🇺🇸Tyler, Texas, United States
Centre d' Oncologie de Gentilly
🇫🇷Nancy, France
Texas Oncology - Sherman
🇺🇸Sherman, Texas, United States
Virginia Oncology Associates
🇺🇸Newport News, Virginia, United States
Klinikum Kassel GmbH Medizinische Klinik IV Onkologie, Hämatologie, Immunologie
🇩🇪Kassel, Hessen, Germany
Schwerpunktpraxis für Hämatologie und Onkologie
🇩🇪Magdeburg, Germany
Northwest Alabama Cancer Center
🇺🇸Florence, Alabama, United States
Pacific Medical Center
🇺🇸Anaheim, California, United States
Comprehensive Blood and Cancer Center
🇺🇸Bakersfield, California, United States
UCSD Moores Cancer Center
🇺🇸La Jolla, California, United States
University of Hawaii Cancer Center
🇺🇸Honolulu, Hawaii, United States
AMPM Research Clinic
🇺🇸Miami Gardens, Florida, United States
Indiana University Cancer Center
🇺🇸Beech Grove, Indiana, United States
Henry Ford Health System
🇺🇸Detroit, Michigan, United States
Oncology Hematology West PC dba Nebraska Cancer Specialists
🇺🇸Omaha, Nebraska, United States
Willamette Valley Cancer Institute and Research Center
🇺🇸Eugene, Oregon, United States
Signal Point Hematology/Oncology
🇺🇸Middletown, Ohio, United States
New York Oncology, Hematology, P.C.
🇺🇸Hudson, New York, United States
Toledo Community Oncology Program- Toledo Community Hospital
🇺🇸Toledo, Ohio, United States
Cancer Centers of the Carolinas
🇺🇸Spartanburg, South Carolina, United States
Texas Oncology Denton South
🇺🇸Denton, Texas, United States
Mary Crowley Cancer Research Center
🇺🇸Dallas, Texas, United States
Cancer Care Centers of South Texas
🇺🇸San Antonio, Texas, United States
Oncology and Hematology Associates of Southwest Virginia, Inc., dba Blue Ridge Cancer Care
🇺🇸Roanoke, Virginia, United States
Medizinisches Versorgungszentrum Ãrzteforum Seestrabe
🇩🇪Berlin, Germany
Ãrzteforum Henningsdorf Darmzentrum Oberhavel
🇩🇪Hennigsdorf, Germany
Universitaetsklinikum Ulm
🇩🇪Ulm, Germany
Petruskrankenhaus Wuppertal, Klinik fuer Innere Medizin II- Gastroenterologie, Hepatologie und Diabetologie
🇩🇪Wuppertal, Germany
Universitätsklinikum Köln - Studienzentrum der Klinik I für Innere Medizin
🇩🇪Koeln, Nordrhein Westfalen, Germany
Fundacion de Investigacion de Diego
🇵🇷San Juan, Puerto Rico