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

This study has been completed.
Sponsor:
Information provided by:
Biothera
ClinicalTrials.gov Identifier:
NCT00545545
First received: October 16, 2007
Last updated: March 30, 2010
Last verified: March 2010
  Purpose

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.


Condition Intervention Phase
Recurrent Colorectal Carcinoma
Progressive Colorectal Carcinoma
Biological: Safety and efficacy of escalating doses
Biological: Safety and efficacy of escalating doses.
Phase 1
Phase 2

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

Resource links provided by NLM:


Further study details as provided by Biothera:

Primary Outcome Measures:
  • 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. [ Time Frame: Prospective ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • To determine the pharmacokinetic (PK) profile of Imprime PGG administered in combination with cetuximab with concomitant irinotecan therapy in patients with colorectal cancer. [ Time Frame: Prospective ] [ Designated as safety issue: No ]
  • 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. [ Time Frame: Prospective ] [ Designated as safety issue: No ]

Estimated Enrollment: 48
Study Start Date: October 2007
Study Completion Date: December 2009
Primary Completion Date: December 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Arm 1, Cohort 1
2.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
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.
Experimental: Arm 1, Cohort 2
4.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
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.
Experimental: Arm 1, Cohort 3
6.0 mg/kg Imprime PGG administered weekly with combination therapy of cetuximab and irinotecan.
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.
Experimental: Arm 2, Cohort 1
2.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Biological: 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.
Experimental: Arm 2, Cohort 2
4.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Biological: 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.
Experimental: Arm 2, Cohort 3
6.0 mg/kg Imprime PGG administered weekly with concomitant cetuximab.
Biological: 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.

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  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: NCT00545545

Locations
Philippines
Medical City
Makati City, Philippines
Philippine General Hospital
Manila, Philippines
Sponsors and Collaborators
Biothera
Investigators
Principal Investigator: Ma. Belen Tamayo, MD The Medical City Hospital
Principal Investigator: Gerardo Cornelio, MD, FPCP/FPS Philippines General Hospital
  More Information

No publications provided

Responsible Party: Michele Gargano, VP Clinical Development, Biothera
ClinicalTrials.gov Identifier: NCT00545545     History of Changes
Other Study ID Numbers: BT-CL-PGG-CRC0713
Study First Received: October 16, 2007
Last Updated: March 30, 2010
Health Authority: Philippines: Bureau of Food and Drugs

Keywords provided by Biothera:
Colorectal
Carcinoma
Recurrent
Progressive
Cetuximab
Irinotecan
5-Fluorouracil

Additional relevant MeSH terms:
Carcinoma
Colorectal Neoplasms
Colonic Diseases
Digestive System Diseases
Digestive System Neoplasms
Gastrointestinal Diseases
Gastrointestinal Neoplasms
Intestinal Diseases
Intestinal Neoplasms
Neoplasms
Neoplasms by Histologic Type
Neoplasms by Site
Neoplasms, Glandular and Epithelial
Rectal Diseases
Cetuximab
Irinotecan
Antineoplastic Agents
Antineoplastic Agents, Phytogenic
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Radiation-Sensitizing Agents
Therapeutic Uses
Topoisomerase I Inhibitors
Topoisomerase Inhibitors

ClinicalTrials.gov processed this record on November 20, 2014