Clinical Trials /

Re-challenge Therapy With Chemotherapy & Panitumumab in Metastatic Colorectal Cancer Patients Treated With an Anti-EGFR

NCT03940131

Description:

patients with metastatic colorectal cancer who were initially RAS wild and failed at least 2 lines of chemotherapy will be enrolled. Anti-EGFR must have been given in 1st line. Those who remain RAS-wild upon retesting will receive rechallenge with panitumumab and chemotherapy

Related Conditions:
  • Colorectal Adenocarcinoma
Recruiting Status:

Not yet recruiting

Phase:

Phase 2

Trial Eligibility

Document

Title

  • Brief Title: Re-challenge Therapy With Chemotherapy and Panitumumab in Metastatic Colorectal Cancer Patients Treated With an Anti-EGFR Therapy in 1st Line Treatment: a Phase II Multicentre Study.
  • Official Title: Re-challenge Therapy With Chemotherapy and Panitumumab in Metastatic Colorectal Cancer Patients Treated With an Anti-EGFR Therapy in 1st Line Treatment: a Phase II Multicentre Study.

Clinical Trial IDs

  • ORG STUDY ID: 19-504
  • NCT ID: NCT03940131

Conditions

  • Metastatic Colorectal Cancer

Interventions

DrugSynonymsArms
PanitumumabFolfox, FolfiriSingle Arm

Purpose

patients with metastatic colorectal cancer who were initially RAS wild and failed at least 2 lines of chemotherapy will be enrolled. Anti-EGFR must have been given in 1st line. Those who remain RAS-wild upon retesting will receive rechallenge with panitumumab and chemotherapy

Detailed Description

      This is a single arm pilot multicenter prospective study. We will recruit KRAS/RAS wild
      metastatic colorectal cancer patients who received at least 2 lines of chemotherapy and the
      1st line must include cetuximab/panitumumab combined with chemotherapy. We will repeat RAS
      testing after progression on the last line of therapy. RAS testing will be taken via liquid
      biopsy using ctDNA or tissue biopsy from either a new tumour lesion or a previously present
      lesion which shows evidence of disease progression by radiological imaging. Only RAS-wild
      patients upon re-testing will be enrolled and will receive re-challenge therapy with
      panitumumab combined with chemotherapy similar to that given at 1st line
      (5-fluorouracil/leucoverin combined with oxaliplatin or irinotecan). Those converted to RAS
      mutant will not be enrolled.

      All patients will be treated until disease progression, unacceptable toxic effects or
      withdrawal of consent.
    

Trial Arms

NameTypeDescriptionInterventions
Single ArmExperimentalPanitumumab with FOLFOX6/FOLFIRI
  • Panitumumab

Eligibility Criteria

        Inclusion Criteria:

          -  Histologically confirmed metastatic adenocarcinoma of the colon or rectum with
             initially KRAS/RAS wild tumours.

          -  Patients received at least 2 lines of chemotherapy including a fluoropyrimidine,
             irinotecan and oxaliplatin± bevacizumab.

          -  First line chemotherapy regimen with a fluoropyrimidine and irinotecan or
             fluoropyrimidine and oxaliplatin in addition to an anti-EGFR agent
             (cetuximab/panitumumab).

          -  No evidence of disease progression for at least 4 months from the start of 1st line
             therapy.

          -  At least one measurable lesion ≥ 10 mm as assessed by CT-scan or MRI must be available
             and accessible for re-biopsy and RAS testing.

          -  Repeated RAS testing before re-challenge therapy must be done.

          -  Age ≥18 years.

          -  ECOG Performance status (PS) 0-2.

          -  The patient has adequate organ function, defined as : Absolute neutrophil count (ANC)
             ≥ 1.5 x 109/L, hemoglobin ≥ 9 g/dl, and platelets ≥ 100 x 109/L. Total bilirubin ≤ 1.5
             times upper limit of normal value (ULN), serum alkaline phosphatase level < 5 times
             ULN, Serum creatinine level <1.5 mg/dl.

          -  For female patients of childbearing potential, negative pregnancy test within 7 days
             before starting the study treatment.

          -  Subject must provide informed consent prior to initiation of any study specific
             activities/procedures

        Exclusion Criteria:

          -  Significant cardiovascular disease including unstable angina or myocardial infarction
             within 12 months before initiation of study treatment or a history of ventricular
             arrhythmia (treated or not).

          -  History or evidence of central nervous system metastasis (CT-scan or MRI are not
             mandatory if no clinical symptoms).

          -  Known allergy or hypersensitivity to panitumumab.

          -  Patients with right-sided colon cancer originating from the ascending colon or hepatic
             flexure.

          -  Patients with known MSI-high status.

          -  Patients with known HER2-positive status.

          -  Previous or concurrent malignancy except for basal or squamous cell skin cancer, in
             situ carcinoma of the cervix, low-risk prostate cancer according to d'Amico
             classification or other solid tumors treated curatively and without evidence of
             recurrence for at least 5 years prior to the study.

          -  Active or uncontrolled clinically serious infection.

          -  Known human immunodeficiency virus (HIV) infection or acquired immunodeficiency
             syndrome (AIDS)-related illness.

          -  Other serious and uncontrolled non-malignant disease.

          -  Pregnancy.

          -  Breast feeding.

          -  Treatment with any other investigational medicinal product within 28 days prior to
             study entry.

          -  Concomitant administration of live, attenuated virus vaccine such as yellow fever
             vaccine.
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Overall response rate (ORR)
Time Frame:3 years
Safety Issue:
Description:defined as the proportion of patients with tumour response (complete response or partial response) by RECIST criteria 1.1.

Secondary Outcome Measures

Measure:Disease control rate (DCR)
Time Frame:3 years
Safety Issue:
Description:defined as the proportion of patients with tumour response (complete response or partial response) or tumour stabilization during study treatment.
Measure:Progression-free survival (PFS)
Time Frame:3 years
Safety Issue:
Description:defined as the time from the date of starting the study treatment regimen till the date of the first disease progression after re-challenge therapy or death (any cause).
Measure:Overall survival (OS)
Time Frame:3 years
Safety Issue:
Description:defined as the time from the date of starting the study treatment regimen to the date of patient death, due to any cause, or to the last date at which the patient was known to be alive.

Details

Phase:Phase 2
Primary Purpose:Interventional
Overall Status:Not yet recruiting
Lead Sponsor:King Abdullah Medical City

Trial Keywords

  • re-challenge
  • panitumumab

Last Updated