mestatic colorectal cancer MedDRA version: 12.1 Level: LLT Classification code 10052358 Term: Colorectal cancer metastatic
Conditions
Interventions
Product Name: PEG-SN38
Product Code: EZN-2208
Pharmaceutical Form: Powder and solvent for solution for infusion
INN or Proposed INN: EZN-2208
CAS Number: 100963-53-7
Current Sponsor code: EZN-2208
Oth
Sponsors
Enzon Pharmaceuticals, Inc
Eligibility
Sex/Gender
All
Inclusion criteria
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
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Secondary Objective: • Evaluate the duration of response for each treatment arm • Evaluate the PFS for Arm A • Evaluate overall survival (OS) for each treatment arm • Evaluate safety and toxicity for each treatment arm • For patients with wild-type K-RAS tumors, benchmark the primary and secondary endpoints observed in Arm B (EZN-2208 + cetuximab) with those observed in Arm C (irinotecan + cetuximab) • If possible, to evaluate the peripheral blood mononuclear cell (PBMC) genotype (e.g., uridine diphosphateglucuronosyl-transferase isoform 1A1 [UGT1A1]) to detect changes in genes that may affect how the anticancer drugs work or are degraded, and to see if these changes affect the study treatment or side effects. Patients may participate in this study even if they do not agree to the molecular profile testing. • If possible, to evaluate biomarkers in a sample of the original tumor biopsy. Patients may participate in this study even if they do not agree to allow the tumor biopsy testing. ;Primary end point(s): Primary Endpoint • Response Rate (RR) for each treatment arm • Progression Free Survival (PFS) for Arms B and C ;Main Objective: For Arms A, B, and C: Determine the overall response rate (RR) of EZN 2208 for two distinct cohorts of patientswith mCRC - Patients with mutated K-RAS tumors (Arm A) - Patients with wild-type K-RAS tumors (Arms B and C) For Arms B and C (wild-type K-RAS tumors): Determine the progression-free survival (PFS) | — |
Countries
Netherlands, United Kingdom
Outcome results
None listed