A phase 2 study of EZN-2208 (PEG-SN38) administered with or without cetuximab in patients with metastatic colorectal carcinoma (mCRC)

Phase 2

Completed

Conditions: colorectal carcinoma
colorectal cancer
10017990

Registration Number: NL-OMON34687

Lead Sponsor: Enzon Pharmaceuticals, Inc.

Brief Summary: Not available

Detailed Description: Not available

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 20

Inclusion Criteria

Patients must meet all of the following criteria to be eligble 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.
4. disease progression.
5. previous therapy with irinotecan, oxaplatin 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 regimes. Biologic agents and target non-cytotoxic therapies do not count with respect to the number of prior regimes.
7. age 18 years and older
8. measurable disease by RECIST version 1.1 is required.: >= 1 tumor with >= 10 mm (assuming computed tomography [CT] slice thickness of 5 mm minimum) If the CT slice thickness is >5 mm, the measurable lesion minimum is 2x 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. ECOG performance status of 0 or 1.
10. Adequate bone marrow, renal and hepatic function. : - Hemoglobin>= 9.0 g/dl (no history of blood transfusion in prior 2 weeks)
- absolute neutrophil count (ANC)>= 1,000/microL
- Platelet count >= 75,000/ microL
- Serum creatinine <= 1.5 times the upper limit of normal (ULN)
- Total bilirubine within normal limits.
- Transaminases (aspartate aminotransferase [AST] and alanine aminotransferase [ALT})<= 2.5 times the ULN (may be <= 5 times the ULN if the increase is due to metastatic disease to the liver)

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 radiotherapy. Patients with previously treated brain metastases who are currently asymptomatic and not requiring steroids are eligble.
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 senory neuropathy) related to administration of an investigational agent, chemotherapy, immunotherapy, surgery, radiotherapy, or other treatments for the cancer.
11. any condition, such as uncontrolled 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 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

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>For Arms A, B, and C: Determine the overall response rate (RR) of EZN-2208 for<br /><br>two distinct cohorts of patients with mCRC<br /><br>- Patients with mutated K-RAS tumors (Arm A)<br /><br>- Patients with wild-type K-RAS tumors (Arms B and C)<br /><br><br /><br>For Arms B and C (wild-type K-RAS tumors): Determine the progression-free<br /><br>survival (PFS)</p><br>

Secondary Outcome Measures