Study of Imprime PGG® in Combination With Cetuximab in Subjects With Recurrent or Progressive KRAS Wild Type Colorectal Cancer

Colorectal Cancer Clinical Trial

— PRIMUS  

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT01309126
• Other study ID #: BT-CL-PGG-CRC1031
• Status: Terminated
• Phase: Phase 3
• First received: February 8, 2011
• Last updated: July 11, 2017
• Start date: April 2011
• Est. completion date: February 2017

Study information

• Verified date: July 2017
• Source: Biothera
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 217
• Est. completion date: February 2017
• Est. primary completion date: February 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Colorectal Cancer
• Colorectal Neoplasms

Intervention

Biological:
• Imprime PGG + cetuximab
Imprime PGG: 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 Cetuximab: initial dose 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)

Drug:
• Cetuximab
Cetuximab: initial dose 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)

Locations

Country	Name	City	State
France	Centre d' Oncologie de Gentilly	Nancy
Germany	Medizinisches Versorgungszentrum Ãrzteforum Seestrabe	Berlin
Germany	Ãrzteforum Henningsdorf Darmzentrum Oberhavel	Hennigsdorf
Germany	Klinikum Kassel GmbH Medizinische Klinik IV Onkologie, Hämatologie, Immunologie	Kassel, Hessen
Germany	Universitätsklinikum Köln - Studienzentrum der Klinik I für Innere Medizin	Koeln, Nordrhein Westfalen
Germany	Schwerpunktpraxis für Hämatologie und Onkologie	Magdeburg
Germany	Universitaetsklinikum Ulm	Ulm
Germany	Petruskrankenhaus Wuppertal, Klinik fuer Innere Medizin II- Gastroenterologie, Hepatologie und Diabetologie	Wuppertal
Puerto Rico	Fundacion de Investigacion de Diego	San Juan
United States	Texas Oncology-Amarillo	Amarillo	Texas
United States	Pacific Medical Center	Anaheim	California
United States	Comprehensive Blood and Cancer Center	Bakersfield	California
United States	Indiana University Cancer Center	Beech Grove	Indiana
United States	Highlands Oncology Group	Bentonville	Arkansas
United States	Dana Farber Cancer Institute	Boston	Massachusetts
United States	Massachusetts General Hospital	Boston	Massachusetts
United States	Providence St. Joseph Medical Center	Burbank	California
United States	Ellis Fischel Cancer Center at University of Missouri- Columbia	Columbia	Missouri
United States	Mary Crowley Cancer Research Center	Dallas	Texas
United States	Texas Oncology - Baylor Charles A. Sammons Cancer Center	Dallas	Texas
United States	Texas Oncology - Dallas Presbyterian Hospital	Dallas	Texas
United States	Texas Oncology Denton South	Denton	Texas
United States	Henry Ford Health System	Detroit	Michigan
United States	Hematology and Oncology Associates of Central NY	East Syracuse	New York
United States	Willamette Valley Cancer Institute and Research Center	Eugene	Oregon
United States	Northwest Alabama Cancer Center	Florence	Alabama
United States	Texas Oncology - Fort Worth	Fort Worth	Texas
United States	Medical and Surgical Specialists	Galesburg	Illinois
United States	The Jones Clinic	Germantown	Tennessee
United States	University of Hawaii Cancer Center	Honolulu	Hawaii
United States	New York Oncology, Hematology, P.C.	Hudson	New York
United States	Tennessee Cancer Specialists	Knoxville	Tennessee
United States	UCSD Moores Cancer Center	La Jolla	California
United States	Texas Oncology - Lewisville	Lewisville	Texas
United States	Kenmar Research Institute	Los Angeles	California
United States	University of Louisville/James Brown Cancer Center	Louisville	Kentucky
United States	AMPM Research Clinic	Miami Gardens	Florida
United States	Signal Point Hematology/Oncology	Middletown	Ohio
United States	University of Minnesota	Minneapolis	Minnesota
United States	Ochsner Clinic Foundation	New Orleans	Louisiana
United States	Virginia Oncology Associates	Newport News	Virginia
United States	Illinois Cancer Specialists	Niles	Illinois
United States	Northern Utah Associates	Ogden	Utah
United States	Oncology Hematology West PC dba Nebraska Cancer Specialists	Omaha	Nebraska
United States	MD Anderson Cancer Center	Orlando	Florida
United States	Providence Portland Medical Center	Portland	Oregon
United States	Oncology and Hematology Associates of Southwest Virginia, Inc., dba Blue Ridge Cancer Care	Roanoke	Virginia
United States	Texas Oncology-Seton Williamson	Round Rock	Texas
United States	Cancer Care Centers of South Texas	San Antonio	Texas
United States	Texas Oncology - Sherman	Sherman	Texas
United States	Cancer Centers of the Carolinas	Spartanburg	South Carolina
United States	Toledo Community Oncology Program- Toledo Community Hospital	Toledo	Ohio
United States	Texas Oncology - Tyler	Tyler	Texas

Sponsors (1)

Lead Sponsor	Collaborator
Biothera

Countries where clinical trial is conducted

United States,  France,  Germany,  Puerto Rico, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Overall Survival (OS)		18 months
Secondary	Progression Free Survival (PFS)		18 months
Secondary	Rate of complete response (CR)		18 months
Secondary	Rate of partial response (PR)		18 months
Secondary	Rate of overall response (CR + PR)		18 months
Secondary	Safety and tolerability of the dosing regimen as measured by the incidence and severity of adverse events observed in study participants		18 months
Secondary	Sparse pharmacokinetic profile of Imprime PGG will be determined to expand current Imprime PGG PK data	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.	18 months
Secondary	Change in Quality of Life		18 months

External Links

•   Sponsor home page