A Phase 2 Study of EZN-2208 (PEG-SN38) administered with or without Cetuximab in patients with Metastatic Colorectal Carcinoma (mCRC)
- Conditions
- Metastatic Colorectal Carcinoma (mCRC)MedDRA version: 13.1 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
- Registration Number
- EUCTR2009-014876-23-GB
- Lead Sponsor
- Enzon Pharmaceuticals, Inc.
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- ot Recruiting
- Sex
- Not specified
- Target Recruitment
- 220
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 (see Appendix 3). 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. Maximum of 2 progressions from the time the patient had metastatic disease.
a. Progression <6 months after completion of adjuvant therapy counts as one of the 2 progressions.
b. Progression before reintroduction of oxaliplatin does not count as one of the 2 progressions if the oxaliplatin-containing regimen had been stopped for reasons other than progression.
7. Age 18 years or older
8. Measurable disease by RECIST Version 1.1 [52] is required: =1 tumor with =10 mm (assuming computed tomography [CT] slice thickness of 5 mm minimum).
9. ECOG performance status of 0 or 1
10. Adequate bone marrow, renal, and hepatic function
• Absolute neutrophil count (ANC) =1,000/µL
• Platelet count =75,000/µL
• Serum creatinine =1.5 times the upper limit of normal (ULN)
• Total bilirubin 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)
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
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. Patients having received adjuvant cetuximab and progressing >12 months after completion of adjuvant cetuximab are eligible for Arms B and C.
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
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method