Efficacy and Safety Study of Imprime PGG With Cetuximab in Subjects With Stage IV KRAS-Mutated Colorectal Cancer

A Phase 2 Efficacy and Safety, Open-label, Multicenter Study of Imprime PGG® Injection in Combination With Cetuximab in Subjects With Stage IV KRAS-Mutated Colorectal Cancer

Study BT-CL-PGG-CRC0821 is a Phase 2, open-label, multicenter, efficacy and safety study. It will be conducted using a two-stage design with the intention of determining the initial efficacy of Imprime PGG in combination with a monoclonal antibody (MAb; cetuximab) in the treatment of KRAS-mutant colorectal cancer (CRC). Both stages will be conducted in subjects with Stage IV CRC demonstrating the KRAS gene mutation. Subjects will dose until progression of disease or discontinuation from the study for other reasons; e.g., safety, non-compliance. Approximately 56 subjects will be enrolled at three participating centers (17 into Stage 1 and 39 into Stage 2).

Study Overview

• Status: Completed
• Conditions: Colorectal Cancer
• Intervention / Treatment: Biological: Imprime PGG

Detailed Description

Study BT-CL-PGG-CRC0821 is a Phase 2, open-label, multicenter, efficacy and safety study. It will be conducted using a two-stage design with the intention of determining the initial efficacy of Imprime PGG in combination with a monoclonal antibody (MAb; cetuximab) in the treatment of KRAS-mutant colorectal cancer (CRC). Both stages will be conducted in subjects with Stage IV CRC demonstrating the KRAS gene mutation. All subjects will receive Imprime PGG at 4 mg/kg and standard doses of cetuximab; Imprime PGG and cetuximab will be administered in 6-week cycles. Subjects will dose until progression of disease or discontinuation from the study for other reasons; e.g., safety, non-compliance. The initial cetuximab dose will be 400 mg/m2 on Cycle 1/Day1 and subsequent doses of cetuximab will be 250 mg/m2 weekly. Imprime PGG will be dosed weekly at 4 mg/kg. Tumor measurements and determination of tumor responses for this study will be performed according to RECIST. Approximately 56 subjects will be enrolled at three participating centers (17 into Stage 1 and 39 into Stage 2). Final results will be determined from combined Stage 1 and Stage 2 data.

• Study Type: Observational
• Enrollment (Actual): 18

Contacts and Locations

Study Locations

• United States
  • Minnesota
    • Minneapolis, Minnesota, United States
      • University of Minnesota
  • New York
    • New York, New York, United States
      • Memorial Sloane-Kettering Cancer Research Center
  • Texas
    • Dallas, Texas, United States
      • Mary Crowley Medical Research Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Approximately 56 patients with Stage IV Kras-mutated colorectal cancer.

Description

Inclusion Criteria:

1. Is >18 years old;
2. Has Stage IV carcinoma of the colon or rectum with documented histological or cytological confirmation;
3. Tumor has known KRAS mutation;
4. Has failed previous irinotecan- and oxaliplatin-containing regimens in either adjuvant or metastatic settings or is intolerant to irinotecan-based therapies;
5. Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST;
6. Has not received any other treatment for colorectal cancer within the 30 days prior to first dose of study treatment under this protocol;
7. Has an ECOG score of 0-1;
8. Has a life expectancy of > 3 months;

9. Has adequate bone marrow reserve as evidenced by:

   1. ANC ≥ 1,500/μL
   2. PLT ≥ 100,000/μL
10. Has adequate renal function as evidenced by serum creatinine ≤ 2.5X the upper limit of normal (ULN) for the reference lab;

11. Has adequate hepatic function as evidenced by:

    1. AST ≤ 3X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
    2. ALT ≤ 3X ULN for the reference lab (≤ 5X ULN for subjects with known hepatic metastases)
    3. Bilirubin < 1.5 mg/dl, OR direct bilirubin < 1.0 mg/dl
    4. Serum Albumin > 3.0 gm/dl
12. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC); and
13. 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 medication (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 or suspected brain metastases;
6. Had a second malignancy within the previous 5 years, except for basal cell carcinoma, cervical intra-epithelial neoplasia or curatively-treated prostate cancer with a PSA of < 2.0 ng/mL;
7. Has known HIV/AIDS, Hepatitis B, Hepatitis C, connective tissue disease, or other clinical diagnosis, ongoing or intercurrent illness that in the investigator's opinion should prevent 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.

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Stage 1	Biological: Imprime PGG; Imprime PGG, 4 mg/kg, i.v. over 2 hr, weekly in 6 week cycles and Cetuximab, initial dose will be 400 mg/m2 via i.v., and subsequent doses will be 250 mg/m2 via i.v., weekly in 6 week cycles; Other Names: Erbitux
Stage 2	Biological: Imprime PGG; Imprime PGG, 4 mg/kg, i.v. over 2 hr, weekly in 6 week cycles and Cetuximab, initial dose will be 400 mg/m2 via i.v., and subsequent doses will be 250 mg/m2 via i.v., weekly in 6 week cycles; Other Names: Erbitux

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Objective response rate (ORR)	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.

Secondary Outcome Measures

Outcome Measure	Time Frame
Disease control rate (DCR) and duration of disease control	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Complete response (CR), partial response (PR), and stable disease (SD) rates	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Duration of objective tumor response	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Duration of stable disease	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Time to progression (TTP)	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Progression-free survival (PFS)	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Safety of the dosing regimen	Assessed after 17 subjects complete 1 treatment cycle and at completion of study.
Overall survival	Assessed after all subjects are deceased or lost to follow-up

Collaborators and Investigators

• Sponsor: HiberCell, Inc.
• Investigators: Principal Investigator: Leonard Saltz, MD, Memorial Sloane-Kettering Cancer Center; Principal Investigator: Neil H. Segal, MD, PhD, Memorial Sloane-Kettering Cancer Center; Principal Investigator: Neil Senzer, MD, Mary Crowley Medical Research Center; Principal Investigator: Purvi Gada, MD, University of Minnesota

Study record dates

Study Major Dates

• Study Start: June 1, 2009
• Primary Completion (Actual): February 1, 2012
• Study Completion (Actual): February 1, 2012

Study Registration Dates

• First Submitted: June 1, 2009
• First Submitted That Met QC Criteria: June 1, 2009
• First Posted (Estimate): June 3, 2009

Study Record Updates

• Last Update Posted (Estimate): February 15, 2012
• Last Update Submitted That Met QC Criteria: February 14, 2012
• Last Verified: February 1, 2012

More Information

Terms related to this study

• Keywords: Immunotherapy; Cetuximab; KRAS mutation; Colorectal; Stage IV; Imprime PGG
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms; Antineoplastic Agents; Antineoplastic Agents, Immunological; Cetuximab
• Other Study ID Numbers: BT-CL-PGG-CRC0821