Clinical trial NCT01309126: Study of Imprime PGG® in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer
Official title: A Phase 3 Open-Label, Randomized, Multicenter Study of Imprime PGG® in Combination With Cetuximab (Erbitux®) in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Colorectal Cancer
Keywords: Colorectal Cancer
KRAS Wild Type
Imprime PGG
Cetuximab
Phase 3
Efficacy
Safety
Recurrent or Progressive KRAS Wild Type Colorectal Cancer
Lead sponsor: HiberCell, Inc.
Sponsor class: INDUSTRY
First posted: 2011-03-04
Enrollment: 217
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.

Eligibility criteria: Inclusion Criteria:

1. Is \>18 years old;
2. Has recurrent or metastatic carcinoma of the colon or rectum with documented histological or cytological confirmation;
3. Must be KRAS WT;
4. Has measurable disease, defined as at least 1 tumor that fulfills the criteria for a target lesion according to RECIST 1.1;
5. 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;
6. Has an Eastern Cooperative Oncology Group (ECOG) score of 0-1, with a life expectancy of \>3 months;
7. Has received at least 2 prior chemotherapeutic regimens for colorectal cancer;
8. Has adequate bone marrow reserve as evidenced by:

   * Absolute neutrophil count ≥1,500/μL
   * Platelets ≥100,000/μL;
9. Has adequate renal function as evidenced by serum creatinine ≤2.5 × the upper limit of normal (ULN) for the reference lab;
10. 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
11. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Independent Ethics Committee (IRB/IEC); and
12. 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).

Exclusion Criteria:

1. Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
2. Has a known hypersensitivity to baker's yeast or has an active yeast infection;
3. Has had previous exposure to Betafectin® or Imprime PGG;
4. Has an active, uncontrolled infection;
5. Has known untreated or symptomatic brain metastases;
6. 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;
7. 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;
8. If female, is pregnant or breast-feeding;
9. 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
10. Has previously received an organ or progenitor/stem cell transplant.

Primary outcomes:
measure: Overall Survival (OS)
timeFrame: 18 months
Secondary outcomes:
measure: Progression Free Survival (PFS)
timeFrame: 18 months
measure: Rate of complete response (CR)
timeFrame: 18 months
measure: Rate of partial response (PR)
timeFrame: 18 months
measure: Rate of overall response (CR + PR)
timeFrame: 18 months
measure: Safety and tolerability of the dosing regimen as measured by the incidence and severity of adverse events observed in study participants
timeFrame: 18 months
measure: Sparse pharmacokinetic profile of Imprime PGG will be determined to expand current Imprime PGG PK data
timeFrame: 18 months
measure: Change in Quality of Life
timeFrame: 18 months
Other outcomes:
Locations:
city: Florence
country: United States
facility: Northwest Alabama Cancer Center
state: Alabama
city: Bentonville
country: United States
facility: Highlands Oncology Group
state: Arkansas
city: Anaheim
country: United States
facility: Pacific Medical Center
state: California
city: Bakersfield
country: United States
facility: Comprehensive Blood and Cancer Center
state: California
city: Burbank
country: United States
facility: Providence St. Joseph Medical Center
state: California
city: La Jolla
country: United States
facility: UCSD Moores Cancer Center
state: California
city: Los Angeles
country: United States
facility: Kenmar Research Institute
state: California
city: Miami Gardens
country: United States
facility: AMPM Research Clinic
state: Florida
city: Orlando
country: United States
facility: MD Anderson Cancer Center
state: Florida
city: Honolulu
country: United States
facility: University of Hawaii Cancer Center
state: Hawaii
city: Galesburg
country: United States
facility: Medical and Surgical Specialists
state: Illinois
city: Niles
country: United States
facility: Illinois Cancer Specialists
state: Illinois
city: Beech Grove
country: United States
facility: Indiana University Cancer Center
state: Indiana
city: Louisville
country: United States
facility: University of Louisville/James Brown Cancer Center
state: Kentucky
city: New Orleans
country: United States
facility: Ochsner Clinic Foundation
state: Louisiana
city: Boston
country: United States
facility: Massachusetts General Hospital
state: Massachusetts
city: Boston
country: United States
facility: Dana Farber Cancer Institute
state: Massachusetts
city: Detroit
country: United States
facility: Henry Ford Health System
state: Michigan
city: Minneapolis
country: United States
facility: University of Minnesota
state: Minnesota
city: Columbia
country: United States
facility: Ellis Fischel Cancer Center at University of Missouri- Columbia
state: Missouri
city: Omaha
country: United States
facility: Oncology Hematology West PC dba Nebraska Cancer Specialists
state: Nebraska
city: East Syracuse
country: United States
facility: Hematology and Oncology Associates of Central NY
state: New York
city: Hudson
country: United States
facility: New York Oncology, Hematology, P.C.
state: New York
city: Middletown
country: United States
facility: Signal Point Hematology/Oncology
state: Ohio
city: Toledo
country: United States
facility: Toledo Community Oncology Program- Toledo Community Hospital
state: Ohio
city: Eugene
country: United States
facility: Willamette Valley Cancer Institute and Research Center
state: Oregon
city: Portland
country: United States
facility: Providence Portland Medical Center
state: Oregon
city: Spartanburg
country: United States
facility: Cancer Centers of the Carolinas
state: South Carolina
city: Germantown
country: United States
facility: The Jones Clinic
state: Tennessee
city: Knoxville
country: United States
facility: Tennessee Cancer Specialists
state: Tennessee
city: Amarillo
country: United States
facility: Texas Oncology-Amarillo
state: Texas
city: Dallas
country: United States
facility: Mary Crowley Cancer Research Center
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Dallas Presbyterian Hospital
state: Texas
city: Dallas
country: United States
facility: Texas Oncology - Baylor Charles A. Sammons Cancer Center
state: Texas
city: Denton
country: United States
facility: Texas Oncology Denton South
state: Texas
city: Fort Worth
country: United States
facility: Texas Oncology - Fort Worth
state: Texas
city: Lewisville
country: United States
facility: Texas Oncology - Lewisville
state: Texas
city: Round Rock
country: United States
facility: Texas Oncology-Seton Williamson
state: Texas
city: San Antonio
country: United States
facility: Cancer Care Centers of South Texas
state: Texas
city: Sherman
country: United States
facility: Texas Oncology - Sherman
state: Texas
city: Tyler
country: United States
facility: Texas Oncology - Tyler
state: Texas
city: Ogden
country: United States
facility: Northern Utah Associates
state: Utah
city: Newport News
country: United States
facility: Virginia Oncology Associates
state: Virginia
city: Roanoke
country: United States
facility: Oncology and Hematology Associates of Southwest Virginia, Inc., dba Blue Ridge Cancer Care
state: Virginia
city: Nancy
country: France
facility: Centre d' Oncologie de Gentilly
city: Berlin
country: Germany
facility: Medizinisches Versorgungszentrum Ãrzteforum Seestrabe
city: Hennigsdorf
country: Germany
facility: Ãrzteforum Henningsdorf Darmzentrum Oberhavel
city: Kassel, Hessen
country: Germany
facility: Klinikum Kassel GmbH Medizinische Klinik IV Onkologie, Hämatologie, Immunologie
city: Koeln, Nordrhein Westfalen
country: Germany
facility: Universitätsklinikum Köln - Studienzentrum der Klinik I für Innere Medizin
city: Magdeburg
country: Germany
facility: Schwerpunktpraxis für Hämatologie und Onkologie
city: Ulm
country: Germany
facility: Universitaetsklinikum Ulm
city: Wuppertal
country: Germany
facility: Petruskrankenhaus Wuppertal, Klinik fuer Innere Medizin II- Gastroenterologie, Hepatologie und Diabetologie
city: San Juan
country: Puerto Rico
facility: Fundacion de Investigacion de Diego
Study officials:
References: