Safety/Efficacy Study of Imprime PGG With Cetuximab in Patients With Recurrent/Progressive Colorectal Carcinoma

A Phase 1b, Safety, PK, and Efficacy, Multicenter, Dose-Escalating Study of Imprime PGG in Combination With Cetuximab With and Without Irinotecan Therapy in Patients With Recurrent/Progressive Colorectal Carcinoma Following Treatment With a 5-FU Regimen.

Phase 1b, safety, pharmacokinetic, and efficacy, multicenter, dose-escalating Study of Imprime PGG™ Injection dosed in combination with Cetuximab and concomitant irinotecan therapy. Enrolled patients will have a confirmed diagnosis of recurrent or progressive colorectal carcinoma following treatment with a 5-fluorouracil-containing regimen.

Inclusion Criteria:

1. Is between the ages of 18 and 75 years old, inclusive;

2. Has a recurrent or progressive carcinoma of the colon or rectum with documented histological confirmation of primary carcinoma;

3. Has measurable disease, defined as at least one tumor that fulfills the criteria for a target lesion according to RECIST;

4. Has previously received treatment with 5-FU, alone or in combination with other anti-tumor medications (except as in exclusion #1 below); Prior treatment with capecitabine (Xeloda®) will be considered to fulfill the requirement for prior treatment with 5-FU;

5. Has a Karnofsky Score of ≥ 70;

6. Has a life expectancy of > 3 months;

7. Has adequate bone marrow reserve as evidenced by:

   1. ANC ≥ 1,500/μL
   2. PLT ≥ 100,000/μL
   3. HGB ≥ 9 g/dl;

8. Has adequate renal function as evidenced by serum creatinine ≤ 1.5X the upper limit of normal (ULN) for the reference lab;

9. Has adequate hepatic function as evidenced by:

   1. Serum total bilirubin ≤ 1.0 mg/dL
   2. AST ≤ 3X ULN for the reference lab (≤ 5X ULN for patients with known hepatic metastases)
   3. ALT ≤ 3X ULN for the reference lab (≤ 5X ULN for patients with known hepatic metastases);

10. Has discontinued any CYP3A4 enzyme-inducing anticonvulsants (such as phenytoin, phenobarbital or carbamazepine) and antimicrobials (such as refampin and rifabutin), St. John's Wort, and ketoconasole at least two weeks prior to Day 1

11. Has recovered from the effects of any prior surgery, radiotherapy, or chemotherapy;

12. Has read, understood and signed the informed consent form (ICF) approved by the Independent Review Board/Ethics Committee (IRB/EC); and

13. If a woman of childbearing potential or a fertile man (and his partners), must agree to use an effective form of contraception during the study and for 120 days following the last dose of study medication (an effective form of contraception is an hormonal contraceptive or a double-barrier method).

Exclusion Criteria:

1. Has previously received treatment with cetuximab or irinotecan;
2. Has a known hypersensitivity to cetuximab, murine proteins, or any component of cetuximab;
3. Has a hereditary fructose intolerance;
4. Has a known hypersensitivity to baker's yeast, or has an active yeast infection;
5. Has had previous exposure to Betafectin® or Imprime PGG;
6. Has received previous radiation therapy to >30% of active bone marrow;
7. Has a fever of >38.5º C within 3 days prior to initial dosing;
8. Has known or suspected central nervous system (CNS) metastases;
9. 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;
10. Has known HIV/AIDS, Hepatitis B, Hepatitis C, connective tissue or autoimmune disease, or other clinical diagnosis, ongoing or intercurrent illness that in the investigator's opinion would prevent participation;
11. If female, is pregnant or breast-feeding;
12. Is receiving concurrent investigational therapy or has received investigational 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
13. Has previously received an organ or progenitor/stem cell transplant.