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

  • Resize font
  • Print
  • Email
  • Facebook
  • Twitter
  • Google+
  • Pinterest

Basic Trial Information

PhaseTypeAgeTrial IDs
Phase IIIBiomarker/Laboratory analysis, Treatment18 and overBT-CL-PGG-CRC1031
NCI-2011-00967, NCT01309126

Trial Description

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.

Further Study Information

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:

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.

Exclusion 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.

Trial Contact Information

Trial Lead Organizations / Sponsors / Collaborators

Biothera

    Trial Sites

    U.S.A.

    California
    San Diego

    University of California San Diego

    Tony R Reid
    Principal Investigator

    Hawaii
    Honolulu

    University of Hawaii Cancer Center

    Jared D. Acoba
    Principal Investigator

    Massachusetts
    Boston

    Dana-Farber Cancer Institute

    Jeffrey A. Meyerhardt
    Principal Investigator

    Link to the current ClinicalTrials.gov record.
    NLM Identifer NCT01309126

    Note: Information about participating sites on pharmaceutical industry trials may be incomplete. Please visit the ClinicalTrials.gov record via the link above for more information about participating sites.