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

Phase 1

Completed

• Conditions: Recurrent Colorectal Carcinoma; Progressive Colorectal Carcinoma
• Interventions: Biological: Safety and efficacy of escalating doses; Biological: Safety and efficacy of escalating doses.; Biological: Imprime PGG 2 mg/kg; Biological: Imprime PGG 4 mg/kg; Biological: Cetuximab; Drug: Irinotecan; Biological: Imprime PGG 6mg/kg

• Registration Number: NCT00545545
• Lead Sponsor: HiberCell, Inc.

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study Start: 2007-10
• Study First Submitted: 2007-10-16
• Study First Submitted QC: 2007-10-16
• Study First Posted: 2007-10-17
• Primary Completion: 2009-12
• Study Completion: 2009-12
• Results First Submitted: 2018-10-22
• Status Verified: 2025-03
• Results First Submitted QC: 2025-03-12
• Last Update Submitted: 2025-03-12
• Results First Posted: 2025-03-19
• Last Update Posted: 2025-03-19

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 32

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Arm 1, Cohort 1	Safety and efficacy of escalating doses	2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Arm 1, Cohort 2	Safety and efficacy of escalating doses	4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Arm 1, Cohort 3	Safety and efficacy of escalating doses	6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Arm 2, Cohort 1	Safety and efficacy of escalating doses.	2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Arm 2, Cohort 2	Safety and efficacy of escalating doses.	4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Arm 2, Cohort 3	Safety and efficacy of escalating doses.	6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Imprime PGG 2mg/kg+Cetuximab+Irinotecan	Imprime PGG 2 mg/kg	Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 2mg/kg+Cetuximab+Irinotecan	Cetuximab	Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 2mg/kg+Cetuximab+Irinotecan	Irinotecan	Treatment Arm 1 2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 4mg/kg+Cetuximab+Irinotecan	Imprime PGG 4 mg/kg	Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 4mg/kg+Cetuximab+Irinotecan	Cetuximab	Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 4mg/kg+Cetuximab+Irinotecan	Irinotecan	Treatment Arm 1 4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 6mg/kg+Cetuximab+Irinotecan	Cetuximab	Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 6mg/kg+Cetuximab+Irinotecan	Irinotecan	Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 6mg/kg+Cetuximab+Irinotecan	Imprime PGG 6mg/kg	Treatment Arm 1 6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
Imprime PGG 2mg/kg+Cetuximab	Imprime PGG 2 mg/kg	Treatment Arm 2 2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Imprime PGG 2mg/kg+Cetuximab	Cetuximab	Treatment Arm 2 2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Imprime PGG 4mg/kg+Cetuximab	Imprime PGG 4 mg/kg	Treatment Arm 2 4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Imprime PGG 4mg/kg+Cetuximab	Cetuximab	Treatment Arm 2 4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Imprime PGG 6mg/kg+Cetuximab	Cetuximab	Treatment Arm 2 6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Imprime PGG 6mg/kg+Cetuximab	Imprime PGG 6mg/kg	Treatment Arm 2 6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.

Primary Outcome Measures

Name	Time	Method
Safety and Maximum Tolerated Dosage of Imprime PGG When Used in Combination With Cetuximab With or Without Irinotecan Therapy	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	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).

Secondary Outcome Measures

Name	Time	Method
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	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	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.
Overall Response Rate (ORR) Per RECIST Criteria v1.0 in Each Study Arm	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	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.
Disease Control Rate (DCR) Per RECIST Criteria v1.0 in Each Study Arm	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	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.
Duration of Time-to-Progression (TTP) in Each Study Arm	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	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).
Duration of Overall Tumor Response in Each Study Arm	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	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).
Duration of Disease Control in Each Study Arm	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	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).

Trial Locations

Locations (2)

Medical City; 🇵🇭 Makati City, Philippines

Philippine General Hospital; 🇵🇭 Manila, Philippines