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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Biothera
ClinicalTrials.gov Identifier:
NCT00912327
First received: June 1, 2009
Last updated: February 14, 2012
Last verified: February 2012
  Purpose

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).


Condition Intervention
Colorectal Cancer
Biological: Imprime PGG

Study Type: Observational
Study Design: Observational Model: Cohort
Time Perspective: Prospective
Official Title: 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

Resource links provided by NLM:


Further study details as provided by Biothera:

Primary Outcome Measures:
  • Objective response rate (ORR) [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Disease control rate (DCR) and duration of disease control [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Complete response (CR), partial response (PR), and stable disease (SD) rates [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Duration of objective tumor response [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Duration of stable disease [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Time to progression (TTP) [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Progression-free survival (PFS) [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Safety of the dosing regimen [ Time Frame: Assessed after 17 subjects complete 1 treatment cycle and at completion of study. ] [ Designated as safety issue: No ]
  • Overall survival [ Time Frame: Assessed after all subjects are deceased or lost to follow-up ] [ Designated as safety issue: No ]

Biospecimen Retention:   Samples With DNA

Tumor tissue samples from previous biopsies and blood plasma will be collected.


Enrollment: 18
Study Start Date: June 2009
Study Completion Date: February 2012
Primary Completion Date: February 2012 (Final data collection date for primary outcome measure)
Groups/Cohorts Assigned Interventions
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:
  • Imprime PGG
  • 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:
  • Imprime PGG
  • Erbitux

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population

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

Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00912327

Locations
United States, Minnesota
University of Minnesota
Minneapolis, Minnesota, United States
United States, New York
Memorial Sloane-Kettering Cancer Research Center
New York, New York, United States
United States, Texas
Mary Crowley Medical Research Center
Dallas, Texas, United States
Sponsors and Collaborators
Biothera
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 - Clinical and Translational Science Institute
  More Information

No publications provided

Responsible Party: Biothera
ClinicalTrials.gov Identifier: NCT00912327     History of Changes
Other Study ID Numbers: BT-CL-PGG-CRC0821
Study First Received: June 1, 2009
Last Updated: February 14, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Biothera:
Colorectal
KRAS mutation
Stage IV
Imprime PGG
Cetuximab
Immunotherapy

Additional relevant MeSH terms:
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Site
Rectal Diseases
Cetuximab
Antineoplastic Agents
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 21, 2014