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.

Study Overview

• Status: Completed
• Conditions: Recurrent Colorectal Carcinoma; Progressive Colorectal Carcinoma
• Intervention / Treatment: Biological: Imprime PGG 2 mg/kg; Biological: Cetuximab; Drug: Irinotecan; Biological: Imprime PGG 4 mg/kg; Biological: Imprime PGG 6mg/kg

• Study Type: Interventional
• Enrollment (Actual): 32
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Philippines
  • Makati City, Philippines
    • Medical City
  • Manila, Philippines
    • Philippine General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

6

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Imprime PGG 2mg/kg+Cetuximab+Irinotecan; Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.	Biological: Imprime PGG 2 mg/kg; Infusion of 2mg/kg on Day 1 of each week for 6 weeks (one cycle) Number of Cycles: until progression or unacceptable toxicity develops.; Biological: Cetuximab; Infusion 400 mg/m2 over 2 hours on Day 1, then 250 mg/m2 over 1 hour on Days 8, 15, 22, 29, and 36 of each 6-week treatment cycle; Drug: Irinotecan; Infusion 125 mg/m2 i.v. over 1.5 hours on Days 1, 8, 15, and 22 of each 6-week treatment cycle
Experimental: Imprime PGG 4mg/kg+Cetuximab+Irinotecan; Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.	Biological: Cetuximab; Infusion 400 mg/m2 over 2 hours on Day 1, then 250 mg/m2 over 1 hour on Days 8, 15, 22, 29, and 36 of each 6-week treatment cycle; Drug: Irinotecan; Infusion 125 mg/m2 i.v. over 1.5 hours on Days 1, 8, 15, and 22 of each 6-week treatment cycle; Biological: Imprime PGG 4 mg/kg; Infusion of 4mg/kg on Day 1 of each week for 6 weeks (one cycle). Number of Cycles: until progression or unacceptable toxicity develops.
Experimental: Imprime PGG 6mg/kg+Cetuximab+Irinotecan; Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.	Biological: Cetuximab; Infusion 400 mg/m2 over 2 hours on Day 1, then 250 mg/m2 over 1 hour on Days 8, 15, 22, 29, and 36 of each 6-week treatment cycle; Drug: Irinotecan; Infusion 125 mg/m2 i.v. over 1.5 hours on Days 1, 8, 15, and 22 of each 6-week treatment cycle; Biological: Imprime PGG 6mg/kg; Infusion of 6mg/kg on Day 1 of each week for 6 weeks (one cycle) Number of Cycles: until progression or unacceptable toxicity develops.
Experimental: Imprime PGG 2mg/kg+Cetuximab; Treatment Arm 2 2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.	Biological: Imprime PGG 2 mg/kg; Infusion of 2mg/kg on Day 1 of each week for 6 weeks (one cycle) Number of Cycles: until progression or unacceptable toxicity develops.; Biological: Cetuximab; Infusion 400 mg/m2 over 2 hours on Day 1, then 250 mg/m2 over 1 hour on Days 8, 15, 22, 29, and 36 of each 6-week treatment cycle;
Experimental: Imprime PGG 4mg/kg+Cetuximab; Treatment Arm 2 4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.	Biological: Cetuximab; Infusion 400 mg/m2 over 2 hours on Day 1, then 250 mg/m2 over 1 hour on Days 8, 15, 22, 29, and 36 of each 6-week treatment cycle; Biological: Imprime PGG 4 mg/kg; Infusion of 4mg/kg on Day 1 of each week for 6 weeks (one cycle). Number of Cycles: until progression or unacceptable toxicity develops.
Experimental: Imprime PGG 6mg/kg+Cetuximab; Treatment Arm 2 6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.	Biological: Cetuximab; Infusion 400 mg/m2 over 2 hours on Day 1, then 250 mg/m2 over 1 hour on Days 8, 15, 22, 29, and 36 of each 6-week treatment cycle; Biological: Imprime PGG 6mg/kg; Infusion of 6mg/kg on Day 1 of each week for 6 weeks (one cycle) Number of Cycles: until progression or unacceptable toxicity develops.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Safety and Maximum Tolerated Dosage of Imprime PGG When Used in Combination With Cetuximab With or Without Irinotecan Therapy	Safety and maximum tolerated dosage (MTD) of Imprime PGG was determined by the Adverse Events Task Force based on the drug-related adverse events experienced by subjects that met the criteria for a dose limiting toxicity (DLT) within a timeframe of the first 3 weeks of treatment and 1 week follow-up. If one in the initial three subjects for a dose group experienced a DLT, three additional subjects were enrolled in that dose group. If two or more subjects in the expanded dose group experienced a DLT, the study was to be stopped and the MTD was defined as the dose prior to the dose at which the DLT was observed. If a DLT occurred in the first dose group (2 mg/kg Imprime PGG), the protocol allowed for the next group to be dosed at a reduced dose of 1 mg/kg Imprime PGG. The dose groups described above were: Dose Group 1 (Imprime PGG 2 mg/kg), Dose Group 2 (Imprime PGG 4 mg/kg), Dose Group 3 (Imprime PGG 6 mg/kg).	From the date of the first dose of study drug to disease progression or until development of a drug toxicity that precludes further protocol treatment, up to 15 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Rate of Number of Participants With Tumor Response of Complete Response (CR), Partial Response (PR), Stable Disease (SD), or Progressive Disease (PD) in Each Study Arm	The best observed overall response rates were defined as the number of participants experiencing a best tumor response of either complete response (CR; disappearance of all target lesions), partial response (PR; >=30% decrease in the sum of diameters of target lesions), stable disease (SD) or progressive disease (PD) based on RECIST criteria v1.0.	From the date of the first dose of study drug to disease progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months
Overall Response Rate (ORR) Per RECIST Criteria v1.0 in Each Study Arm	The overall response rate was defined as the number of participants experiencing a best tumor response of either complete response (CR; disappearance of all target lesions) or partial response (PR; >=30% decrease in the sum of diameters of target lesions) based on RECIST criteria v.1.0. Overall response rate (ORR) = CR + PR.	From the date of the first dose of study drug to disease progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months
Disease Control Rate (DCR) Per RECIST Criteria v1.0 in Each Study Arm	The disease control rate was defined as the number of participants experiencing a best tumor response of either complete response (CR; disappearance of all target lesions), partial response (PR; >=30% decrease in the sum of diameters of target lesions) or stable disease (SD) based on RECIST criteria v.1.0. Disease control rate (DCR) = CR + PR + SD.	From the date of the first dose of study drug to disease progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months
Duration of Time-to-Progression (TTP) in Each Study Arm	Time-to-progression (TTP) was defined as the time from the date of the first dose of study drug to the date of the first documented progression (date of the CT scan where progression was first observed; or where progression was first observed if clinical assessment). Subjects who did not progress were censored at the last objective evaluation (the date of the last CT scan; or last observed clinical assessment).	The time from the date of the first dose of study drug to the date of the first documented progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months
Duration of Overall Tumor Response in Each Study Arm	The duration of objective tumor response was defined as the time from the date of the first documented CT scan showing CR (disappearance of all target lesions) or PR (>=30% decrease in the sum of diameters of target lesions), whichever occurred first, to the date of the first documented progression (date of CT scan where PD was first observed; or where progression was first observed if based on a clinical assessment).	The time from the date of the first dose of study drug to the date of the first documented progression or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months
Duration of Disease Control in Each Study Arm	Duration of stable disease (SD) was to be an efficacy variable, however, duration of disease control was used in place of duration of stable disease, as it is a more clinically meaning measure of the effectiveness of the treatment. Duration of disease control was defined as the time from the date of the first documented CT scan showing CR (disappearance of all target lesions), PR (>=30% decrease in the sum of diameters of target lesions) or SD, whichever occurred first, to the date of the first documented progression (date of CT scan where PD was first observed; or where progression was first observed if based on a clinical assessment).	The time from the date of first dose of study drug to the date of first documented progression, or last objective evaluation of the tumor before treatment discontinuation due to any reason, up to 15 months

Collaborators and Investigators

• Sponsor: HiberCell, Inc.
• Investigators: Principal Investigator: Ma. Belen Tamayo, MD, The Medical City Hospital; Principal Investigator: Gerardo Cornelio, MD, FPCP/FPS, Philippines General Hospital

Study record dates

Study Major Dates

• Study Start: October 1, 2007
• Primary Completion (Actual): December 1, 2009
• Study Completion (Actual): December 1, 2009

Study Registration Dates

• First Submitted: October 16, 2007
• First Submitted That Met QC Criteria: October 16, 2007
• First Posted (Estimated): October 17, 2007

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 12, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Carcinoma; Cetuximab; Irinotecan; Progressive; 5-Fluorouracil; Recurrent; Colorectal
• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Site; Neoplasms; Disease Attributes; Intestinal Diseases; Neoplasms by Histologic Type; Gastrointestinal Neoplasms; Digestive System Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Neoplasms, Glandular and Epithelial; Colonic Diseases; Recurrence; Carcinoma; Colorectal Neoplasms; Antineoplastic Agents, Immunological; Antineoplastic Agents; Molecular Mechanisms of Pharmacological Action; Enzyme Inhibitors; Topoisomerase I Inhibitors; Topoisomerase Inhibitors; Irinotecan; Cetuximab
• Other Study ID Numbers: BT-CL-PGG-CRC0713