Optimal Anti-EGFR Treatment of mCRC Patients With Low-Frequency RAS Mutation

Launched by LUDWIG-MAXIMILIANS - UNIVERSITY OF MUNICH · Jul 24, 2019

Keywords

ClinConnect Summary

This clinical trial is studying a specific treatment for patients with advanced colon or rectal cancer who have a low-level mutation in a gene called RAS. Researchers want to find out if drugs that target the EGFR protein (a type of treatment often used for cancer) can still be effective even when some tumor cells carry a RAS mutation. They believe that while these drugs might help many patients, the benefits could be shorter because the cancer may develop resistance more quickly.

To participate in this trial, patients need to be at least 18 years old and have a confirmed diagnosis of metastatic adenocarcinoma of the colon or rectum that can't be surgically removed. They should not have received chemotherapy for their cancer before, except for a specific short course, and must have a measurable tumor that can be assessed. Throughout the study, participants will receive treatment and regular check-ups to monitor their response to the therapy. It’s important for potential participants to understand the eligibility criteria and discuss any questions with their doctor to see if this trial is right for them.

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Eligibility criteria

• Inclusion Criteria:
• • Histologically confirmed, UICC stage IV metastatic adenocarcinoma of the colon or rectum
• • Primarily non-resectable metastases or surgical resection refused by the patient
• • RAS mutation determined by the local pathology
• • Age ≥18
• • ECOG performance status 0-2
• • Patients suitable for chemotherapy administration
• • Patient's written declaration of consent obtained
• • Estimated life expectancy \> 3 months
• • Presence of at least one measurable reference lesion according to the RECIST 1.1 criteria
• • Primary tumor tissue available and patient consents to storage and molecular and genetic profiling of tumor material. Molecular profiling of blood samples is optionally performed.
• * Adequate bone marrow function:
• • Leukocytes ≥ 3.0 x 109/L with neutrophils ≥ 1.5 x 109/L
• • Thrombocytes ≥ 100 x 109/L
• • Haemoglobin ≥ 5.6 mmol/L (equivalent to 9 g/dL)
• * Adequate hepatic function:
• • Serum bilirubin ≤ 1.5 x upper limit of normal (ULN)
• • ALAT and ASAT ≤ 2.5 x ULN (in the presence of hepatic metastases, ALAT and ASAT ≤ 5 x ULN)
• * Adequate renal function:
• • ▫ Creatinine clearance (calculated according to Cockcroft and Gault) ≥ 50 mL/min
• • No previous chemotherapy for metastatic disease. Patient with need of immediate treatment (high tumor load, symptoms) may have received one application of FOLFIRI prior to study treatment.
• Exclusion Criteria:
• • Previous chemotherapy for metastatic disease with the exception of one cycle of FOLFIRI (e.g. while waiting for the result of RAS mutation frequency).
• • Patients planned to be treated with FOLFOX or another oxaliplatin-based regimen as first-line treatment
• • Primarily resectable metastases and the patient agrees to resection
• • Grade III or IV heart failure (NYHA classification)
• • Medical or psychological impairments associated with restricted ability to give consent or not allowing conduct of the study
• • Previous chemotherapy for the colorectal cancer with the exception of adjuvant treatment, completed at least 6 months before entering the study
• • Participation in an investigational clinical study or experimental drug treatment within 30 days prior to study inclusion or within a period of 5 half-lives of the substances administered in the investigational clinical study or during an experimental drug treatment prior to inclusion in the study, depending on which period is longest
• • Known hypersensitivity or allergic reaction to any of the following substances: 5-fluorouracil, folinic acid, panitumumab, irinotecan, and chemically related substances and/or hypersensitivity to any of the excipients of any of the aforementioned substances including known hypersensitivity reactions to monoclonal antibodies NCI CTCAE Grade ≥ 3.
• • Known hypersensitivity to Chinese hamster ovary cell (CHO) - cellular products or other recombinant human or humanised monoclonal antibodies
• • History of uncontrolled bronchial asthma
• • Patients with interstitial pneumonitis or pulmonary fibrosis
• • Patients with known brain metastasis
• • History of acute or subacute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhoea
• • Symptomatic peritoneal carcinomatosis
• • Severe, non-healing wounds, ulcers or bone fractures
• • Patients with acute or chronic infection requiring systemic therapy
• • Known history of positive testing for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS)
• • Active or chronic Hepatitis B virus (HBV) or hepatitis C virus (HCV) infection (positive HBV surface antigen or HCV RNA if anti-HCV antibody screening test positive; serologic tests required in patients who receive study treatment).
• • Known DPD deficiency (specific screening not required)
• • Known glucuronidation deficiency (Gilbert's syndrome);(specific screening not required
• • Treatment with sorivudine or brivudine within 28 days before study enrollment or requirement for concomitant antiviral treatment with sorivudine or brivudine
• • History of a second primary malignancy during the past 5 years before inclusion in the study or during participation in the study, with the exception of a basal cell or squamous cell carcinoma of the skin or cervical carcinoma in situ, if these were treated curatively.
• • Known previous or ongoing alcohol or drug abuse
• • Pregnant or breast-feeding patients
• • Any other severe concomitant disease or disorder which, in the investigator's opinion, could influence the patient's ability to participate in the study or influence his/her safety during the study or interfere with interpretation of study results
• • Both, absent and restricted legal capacity