Study to investigate the function of three medicinal products (monoclonal antibodies) on a population of patients with colorectal cancer that has spread from its site of origin to another part of the body.
- Conditions
- Metastatic Colorectal CarcinomaMedDRA version: 21.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864Therapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2018-000618-39-IT
- Lead Sponsor
- SYMPHOGEN A/S
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 54
1. Male or female patients, = 18 years of age at the time of obtaining informed consent
2. Patients with histologically- or cytologically-confirmed mCRC
3. Patients with MSI-H/dMMR tumors must have received prior therapy with pembrolizumab, nivolumab, or other PD-1/PD-L1 pathway blocker and must have progressed on that therapy.
4. Patients meeting the protocol definition of TNmCRC assessed by screening blood test (ctDNA):
a. Without RAS (KRAS and NRAS) MAF = 20% for mutations in the following codons:
• Exon 2: codon 12, 13
• Exon 3: codon 59, 61
• Exon 4: codon 117, 146
b. Without BRAF V600E mutation at any MAF
c. Without EGFR-ECD V441D, V441G, S464L, G465E, G465R, S492R mutations at any MAF
5. Patients with mCRC currently not amenable to surgical intervention due to either medical contraindications or non-resectability of the tumor
6. Patients with measurable disease according to RECIST v1.1 (Appendix 5), and willingness to undergo a total of 2 biopsies of a primary or metastatic tumor site(s) considered safely accessible for biopsy
7. Patients must have received at least 2 prior regimens of standard chemotherapy for mCRC and must have been refractory to or failed (includes intolerance to) those regimens. Prior standard chemotherapy may not have included TAS-102 or regorafenib, but must have included all of the following agents (where approved in the country):
a. Fluoropyrimidines, irinotecan, and oxaliplatin
b. An anti-vascular endothelial growth factor (VEGF) pathway inhibitor approved for treatment of mCRC
c. At least one anti-EGFR mAb approved for treatment of mCRC
8. Patients with acquired resistance to commercially available anti-EGFR mAbs approved for the treatment of mCRC. Patients must have:
a. Received treatment with an anti-EGFR for >16 weeks
b. PD documented by imaging or clinical findings < 6 calendar months after cessation of previous anti-EGFR mAb treatment
c. No more than 6 calendar months from last dose of previous anti-EGFR mAb treatment to date of consent for this trial (regardless of the line of therapy in which it was used)
9. Patients with an Eastern Cooperative Oncology Group (ECOG) performance status (PS) of 0 or 1 (or equivalent Karnofsky PS)
10. Patients, male and female, who are either not of childbearing potential or who agree to use a highly effective method of contraception during the study beginning within 2 weeks prior to the first dose and continuing until 3 months after the last dose of IMP.
11. Must have the ability to understand and give written informed consent for participation in this trial, including all evaluations and procedures as specified by this protocol.
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 30
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 24
2. Patients with a prior history any of the following mutations in their tumor at the time of any previous assessment:
a. RAS (KRAS and NRAS) mutations in the following codons:
• Exon 2: codon 12, 13
• Exon 3: codon 59, 61
• Exon 4: codon 117, 146
b. BRAF V600E mutation
c. EGFR-ECD V441D, V441G, S464L, G465E, G465R, S492R mutations
3. Patients with known, untreated central nervous system (CNS) or leptomeningeal metastases, or spinal cord compression; patients with any of these not controlled by prior surgery or radiotherapy, or patients with symptoms suggesting CNS involvement for which treatment is required
4. Patients with an active second malignancy or history of another malignancy within the last 5 years with the exception of:
a. Treated non-melanoma skin cancers
b. Treated carcinoma in situ (e.g., breast, cervix, endometrium) provided CR was achieved at least 5 years prior to study and no additional therapy is ongoing or required during study period)
c. Controlled, superficial carcinoma of the bladder
d. T1a carcinoma of the prostate comprising < 5% of resected tissue and prostate specific antigen (PSA) within normal limits (WNL) since resection
5. Patients with any of the following hematologic abnormalities at baseline*:
a. Hemoglobin < 9.0 g/dL
b. Absolute neutrophil count (ANC) < 1,500 per mm3
c. Platelet count < 100,000 per mm3
6. Patients with any of the following serum chemistry abnormalities at baseline:
a. Total bilirubin > 2.0 × the upper limit of normal (ULN) for the institution
b. Alkaline phosphatase (ALP) > 2.5 × the ULN for the institution (> 5 × ULN if due to hepatic involvement by tumor)
c. Aspartate aminotransferase (AST) or alanine aminotransferase (ALT) > 2.5 × the ULN for the institution (> 5 × ULN if due to hepatic involvement by tumor)
d. Creatinine clearance (CrCl) < 30 mL/min as calculated by the Cockroft-Gault formula
e. Magnesium < 1.2 mg/dL
7. Patients with:
a. Active thrombosis, or a history of deep vein thrombosis (DVT) or pulmonary embolism (PE), within 4 weeks prior to first administration of IMP, unless adequately treated and considered by the Investigator to be stable
b. Active uncontrolled bleeding or a known bleeding diathesis
8. Patients with a known clinically significant cardiovascular disease or condition, including:
a. Need for antiarrhythmic medical therapy for a ventricular arrhythmia or other uncontrolled arrhythmia (patients with controlled atrial fibrillation (heart rate <90) for > 30 days prior to study entry are eligible)
b. Severe conduction disturbance (e.g., 3rd degree heart block)
c. HR-corrected QT interval (QTc interval) = 480 msec (as calculated by Bazet's formula)
d. Uncontrolled hypertension (per the Investigator's discretion)
e. Congestive heart failure currently requiring therapy
f. Class III or IV cardiovascular disease according to the New York Heart Association Functional Classification
g. History of acute coronary syndromes (including myocardial infarction and unstable angina), coronary angioplasty, or stenting within 6 months prior to first administration of IMP
11. Patients with skin rash > Grade 1 from prior anti-EGFR therapy at the time of randomization
15. Patients with inadequate recovery from any prior surgical procedure, or patients having undergone any major surgical procedure within 4 weeks prior to first administration of IMP
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