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

Recurrent Colorectal Carcinoma Clinical Trial

Official title:

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00545545
• Other study ID #: BT-CL-PGG-CRC0713
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: October 16, 2007
• Last updated: March 30, 2010
• Start date: October 2007
• Est. completion date: December 2009

Study information

• Verified date: March 2010
• Source: Biothera
• Contact: n/a
• Is FDA regulated: No
• Health authority: Philippines: Bureau of Food and Drugs
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 48
• Est. completion date: December 2009
• Est. primary completion date: December 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 75 Years

Eligibility

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

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Carcinoma
• Colorectal Neoplasms
• Progressive Colorectal Carcinoma
• Recurrent Colorectal Carcinoma

Intervention

Biological:
• Safety and efficacy of escalating doses
Imprime PGG and Cetuximab on Day 1 of each week for 6 weeks (one cycle) and irinotecan on Day 1 of each week for 4 weeks with a 2-week rest. Number of Cycles: until progression or unacceptable toxicity develops.
• Safety and efficacy of escalating doses.
Imprime PGG and Cetuximab on Day 1 of each week for 6 weeks (one cycle). Number of Cycles: until progression or unacceptable toxicity develops.

Locations

Country	Name	City	State
Philippines	Medical City	Makati City
Philippines	Philippine General Hospital	Manila

Sponsors (1)

Lead Sponsor	Collaborator
Biothera

Country where clinical trial is conducted

Philippines, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To determine safety and maximum tolerated dosage of Imprime PGGwhen used in combination with cetuximab with and without irinotecan therapy in patients with recurrent/progressive colorectal carcinoma previously treated with a 5-FU regimen.		Prospective	No
Secondary	To determine the pharmacokinetic (PK) profile of Imprime PGG administered in combination with cetuximab with concomitant irinotecan therapy in patients with colorectal cancer.		Prospective	No
Secondary	To determine the tumor response rates (complete response, partial response, stable disease, overall response rate), time to progression, duration of overall tumor response, and the duration of stable disease in patients receiving the combination therapy.		Prospective	No