A Phase 2 Study of EZN-2208 (PEG-SN38) Administered With or Without Cetuximab in Patients with Metastatic Colorectal Carcinoma (mCRC)

• Conditions: mestatic colorectal cancer; MedDRA version: 12.1Level: LLTClassification code 10052358Term: Colorectal cancer metastatic

• Registration Number: EUCTR2009-014876-23-NL
• Lead Sponsor: Enzon Pharmaceuticals, Inc

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2009-12-23
• Last Update Posted: 8 April 2013

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 220

Inclusion Criteria

Inclusion Criteria:
Patients must meet all of the following criteria to be eligible for enrollment in the study.
1. Capable of understanding the protocol requirements and risks and providing written informed consent
2. Histologically confirmed CRC adenocarcinoma that is metastatic or locally recurrent CRC that is nonresectable
3. Patients must agree to genetic testing of the original or metastatic CRC tumor biopsy tissue for K-RAS
mutational status. Participation in study requires the availability of the tumor biopsy and written patient consent
for K-RAS genotyping of the tumor tissue. Lack of tumor tissue or patient refusal to allow genotyping makes the patient ineligible for the study.
Note: If a patient’s K-RAS mutational status was tested using the DxS assay before enrolling in this trial, the
patient’s K-RAS mutational test will not be duplicated if it was performed using a validated assay at a certified
laboratory. If a patient’s K-RAS mutational status was tested before enrolling in this trial using
other assays that evaluate mutations in codons 12 or 13, the patient may enroll in the study on the basis of these
results; however, the patient’s K-RAS mutational test will be duplicated using a validated assay at a certified
laboratory. Patients will need to consent to repeat testing of tumor genotype. Lack of tumor tissue or patient
refusal to allow genotyping makes the patient ineligible for the study.
4. Disease progression
5. Previous therapy with irinotecan, oxaliplatin, and fluoropyrimidine either alone or in any combination(s).
Patients must have radiographically documented progressive disease while receiving, or within 3 months of
receiving, these agents alone or in combination.
6. No more than 2 prior cytotoxic chemotherapy regimens. Biologic agents and targeted non-cytotoxic therapies
do not count with respect to the number of prior regimens .
7. Age 18 years or older
8. Measurable disease by RECIST Version 1.1 is required: NLT 1 tumor with NLT 10 mm (assuming computed
tomography slice thickness of 5 mm minimum). If the CT slice thickness is >5 mm, the measurable lesion
minimum is 2× slice thickness. Measurable disease is defined as at least one lesion for which the longest
diameter can be accurately measured. The only evidence of metastasis must not be nonmeasurable disease such
as leptomeningeal disease, ascites, pleural or pericardial effusion, inflammatory breast disease, lymphangitic
involvement of skin or lung, or abdominal masses/abdominal organomegaly identified by physical examination
that is not measureable by reproducible imaging techniques.
9. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1
•Adequate bone marrow, renal, and hepatic function
•Hemoglobin NLT 9.0 g/dL (no history of blood transfusion in the prior 2 weeks)
•Absolute neutrophil count (ANC) NLT 1,000/microlitre
•Platelet count NLT 75,000/microlitre
•Serum creatinine NMT 1.5 times the upper limit of normal (ULN)
•Total bilirubin within normal limits
•Transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [(ALT]) NMT 2.5 times the
•ULN (may be NMT 5 times the ULN if the increase is due to metastatic disease to the liver)

Are the trial subjects under 18? no
Number of subjects for this age range:
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range

Exclusion Criteria

Patients meeting any of the following exclusion criteria will not be eligible for enrollment.
1. Concurrent serious medical illness that could potentially interfere with protocol compliance
2. Previous cancer treatment with cetuximab (Erbitux), panitumumab (Vectibix), or any other anti-EGFR
therapies. Patients previously treated with such therapy who are found to have mutated K-RAS tumors and who
meet all other eligibility criteria are eligible for participation in Arm A of the study.
3. Positive screening pregnancy test or is breast-feeding
4. Female or male patient of reproductive capacity unwilling to use methods appropriate to prevent pregnancy
during this study
5. Known chronic infectious disease, such as acquired immunodeficiency syndrome (AIDS)
6. Major surgery within 3 weeks before study start
7. Known or suspected brain metastases requiring intervention with steroids and/or radiation therapy. Patients
with previously treated brain metastases who are currently asymptomatic and not requiring steroids are eligible.
8. Prior chemotherapy, immunotherapy, non-investigational agent, or other therapy used to treat the cancer within 3 weeks (6 weeks for prior treatment with mitomycin C) before the scheduled administration of EZN-2208
9. History of other primary cancer within 5 years of enrollment, unless
a. Curatively resected non-melanomatous skin cancer, or
b. Curatively resected cervical cancer
10. Lack of recovery to Grade 1 from any reversible side effects (except alopecia or Grade 2 sensory neuropathy) related to the administration of an investigational agent, chemotherapy, immunotherapy, surgery, radiotherapy, or other treatments for the cancer
11. Any condition such as uncontrollable diabetes, uncontrollable hypertension, or active infection that, in the
opinion of the principal investigator (PI) or Enzon, makes the patient unsuitable for the study. The PI must
consider the potential side effects of SN38 therapy when evaluating a prospective study patient previously
treated with irinotecan.
12. Current participation in another clinical study with an investigational agent and/or use of an investigational
drug (not including investigational use of an approved drug) in the 30 days before the first administration of
EZN-2208
13. Inability to comply with the study protocol

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified