Status:

NOT_YET_RECRUITING

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

Lead Sponsor:

Ludwig-Maximilians - University of Munich

Collaborating Sponsors:

Amgen

ClinAssess GmbH

Conditions:

Treatment Related Cancer

Eligibility:

All Genders

18+ years

Phase:

PHASE2

Brief Summary

The present hypothesis is that anti-EGFR agents are active in tumors with low-level RAS mutation when the majority of tumor cells is still sensitive. While response rate may be high and may reflect se...

Eligibility Criteria

Inclusion

  • 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

  • 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

Key Trial Info

Start Date :

August 1 2019

Trial Type :

INTERVENTIONAL

Allocation :

ESTIMATED

End Date :

August 1 2026

Estimated Enrollment :

120 Patients enrolled

Trial Details

Trial ID

NCT04034173

Start Date

August 1 2019

End Date

August 1 2026

Last Update

July 26 2019

Active Locations (1)

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Page 1 of 1 (1 locations)

1

Ludwigs Maximialians University

Munich, Germany, 81377