LM-02 Details

A perioperative, single-arm, multicenter, phase-II academical trial to investigate the efficacy and safety of panitumumab in combination with irinotecan/5-fluorouracil/leucovorin (FOLFIRI) in patients with previously untreated, RAS-wild-type, potentially resectable colorectal cancer liver metastases

Start:
10/2012

Contact ABCSG-Trial office

E-mail: info@abcsg.at
Phone: +43 1 408 92 30
Fax: +43 1 409 09 90

Design

LM-02 Design
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Primary objectives:                             

  • To evaluate the efficacy and safety of perioperative treatment including panitumumab and FOLFIRI as first line therapy for mCRC in subjects with potentially resectable liver metastases expressing wild-type RAS.

Secondary objectives:                     

  • To answer unresolved questions in the perioperative setting of potentially resectable mCRC:
  • evaluate the proportion of patients who respond after 4 cycles of therapy without liver tissue damage
  • liver resection rate after neoadjuvant chemotherapy in this potentially curable patient group
  • evaluate perioperative morbidity and mortality
  • evaluate pathological response according to tumor regression rate
  • estimate the progression-free survival (PFS)
  • estimate the overall survival (OS)

Inclusion criteria:

  1. Histologically confirmed metastatic colorectal cancer with potentially resectable liver metastases
  2. Primary tumor in-situ or resected (in case of resected primary tumor, neoadjuvant short-time radiotherapy is allowed if terminated > 14 days prior to registration)
  3. Subjects with wild-type RAS tumor status confirmed by assessment of paraffin embedded tumor tissue from the primary tumor or metastases
  4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Appendix E)
  5. At least one measurable metastatic lesion in the liver as per RECIST 1.1 guidelines (Appendix D) using multislice 3 phase CT
  6. Man or woman > 18 years
  7. Hematologic function, as follows (< 28 days of registration):
    • absolute neutrophil count (ANC) > 1.5 x 109/L
    • leucocyte count > 3.0 x 109g/L
    • platelet count > 100 x 109/L
    • hemoglobin > 9 x g/dL
  8. Renal function, as follows (< 28 days of registration):
    • creatinin < 1.5 x upper limit of normal (ULN)
  9. Hepatic function, as follows (<28 days of registration):
    • aspartate aminotransferase (AST) < 5 x ULN in presence of liver metastases
    • alanine aminotransferase (ALT) < 5 x ULN in presence of liver metastases
    • total bilirubin < 1.5 x ULN
  10. Women of childbearing potential must have a negative pregnancy test done within 1 week before registration
  11. Competent to comprehend, sign, and date an IEC/IRB-approved informed consent form
  12. Life expectancy > 3 months

Exclusion criteria:

  1. Prior chemotherapy for the treatment of current metastatic cancer (including biologics)
  2. Current extrahepatic metastatic disease
  3. Prior chemotherapy and/or resection of any metastases from mCRC <5 years
  4. Prior adjuvant or neoadjuvant (chemo-) therapy for the treatment of colorectal cancer ≤ 26 weeks prior to registration
  5. Radiotherapy ≤ 14 days prior to registration (patients must have recovered from all radiotherapy-related toxicities)
  6. Previous malignancy other than CRC in the last 5 years except basal cell carcinoma of the skin and/or in situ carcinoma of the cervix
  7. Active infection requiring systemic treatment or any uncontrolled infections < 14 days prior to registration
  8. Any investigational agent or therapy < 28 days before registration
  9. Clinically significant cardiovascular disease (including myocardial infarction, unstable angina, symptomatic congestive heart failure, serious uncontrolled cardiac arrhythmia) < 1 year before registration
  10. Known allergy or hypersensitivity to irinotecan, 5-FU, leucovorin or panitumumab
  11. History of severe adverse events to iodinated contrast agents
  12. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on baseline chest CT scan
  13. Known positive test(s) for human immunodeficiency virus (HIV) infection, hepatitis C virus, acute or chronic active hepatitis B infection
  14. Any co-morbid disease or condition that could increase the risk of toxicity
  15. Any uncontrolled concurrent illness or history of any medical condition that may interfere with the interpretation of the study results
  16. Major surgical procedure (requiring general anaesthesia) <28 days – patients must have recovered from surgery-related toxicities
  17. Subject who is pregnant or breast feeding or planning to become pregnant within 6 months after the end of treatment
  18. Woman or man of childbearing potential not consenting to use adequate contraceptive precautions (double barrier contraceptive methods e.g. diaphragm plus condom), or abstinence during the course of the study and 6 months after the last study drug administration
  19. Subject unwilling or unable to comply with study requirements