FOLFOXIRI Plus Panitumumab Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only
Condition: Colorectal Cancer
MeSH terms: Colorectal Neoplasms
Intervention: Panitumumab; Oxaliplatin; Irinotecan; Leucovorin; 5-Fluorouracil
Intervention description: 6 mg/kg, 60-90 minute IV infusion every 2 weeks; 85 mg/m2, 2-hour IV infusion every 2 weeks; 125 mg/m2, 1-hour IV infusion every 2 weeks; 200 mg/m2, 2-hour IV infusion every 2 weeks; 3200 mg/m2 IV, 48-hour continuous infusion every two weeks
Intervention MeSH terms: Leucovorin; Fluorouracil; Oxaliplatin; Irinotecan; Panitumumab
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 15.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: liver-only metastatic KRAS wild-type colorectal cancer; Panitumumab; Oxaliplatin; Irinotecan; Leucovorin; 5-Fluorouracil

Summary:

      In this Phase II study the investigators plan to determine the overall response rate (ORR) of
      the combination of FOLFOXIRI plus panitumumab as first-line treatment of patients with
      liver-only metastatic KRAS wild-type colorectal cancer.
    

Eligibility criteria:

        Inclusion Criteria:

          1. Patient must have a biopsy confirmed adenocarcinoma of the colon or rectum with stage
             IV (metastatic) liver-only disease, as defined by staging with CT scans.

          2. Patients must have a baseline evaluation to determine whether liver metastases are
             resectable (e.g. a single liver metastasis in a resectable location)or unresectable
             (surgical consultation is recommended). Both groups are eligible for this study.

          3. Tumor tissue must reveal wild-type KRAS expression (i.e. no KRAS mutation) prior to
             study entry (see Section 7.4.4.).

          4. Patients must have at least one unidimensional measurable lesion definable by CT scan.
             Disease must be measurable per RECIST version 1.1 criteria (see Section 9).

          5. Eastern Cooperative Oncology Group (ECOG) Performance Status of 0 or 1 (see Appendix
             A).

          6. Laboratory values as follows:

             ANC greater than 1500/μL

             Hgb greater than9 g/dL

             Platelets greater than 100,000/μL

             AST/SGOT less than 5.0 x ULN

             ALT/SGPT less than or equal to 5.0 x ULN

             Alk Phos less than or equal to 5.0 x ULN

             Bilirubin less than or equal to 1.5 x ULN

             Creatinine 1.5 mg/dL or calculated creatinine clearance 50 ml/min

             Magnesium LLN

          7. Patient must have a life expectancy of greater than 12 weeks.

          8. Patient must be greater than or equal to 18 years of age.

          9. Patient must be accessible for treatment and follow-up.

         10. Women of childbearing potential must have a negative serum or urine pregnancy test
             performed less than or equal to 7 days prior to start of treatment. Women of
             childbearing potential or men with partners of childbearing potential must use
             effective birth control measures during treatment and during the 6 months following
             completion of study treatment. If a woman becomes pregnant or suspects she is pregnant
             while participating in this study, she must agree to inform her treating physician
             immediately.

         11. Patient must be able to understand the nature of the study and give written informed
             consent prior to study entry.

        Exclusion Criteria:

          1. Prior systemic therapy for metastatic colorectal cancer (including chemotherapy,
             bevacizumab, cetuximab, panitumumab, and other targeted agents).

          2. Adjuvant chemotherapy (and/or chemoradiation) for colorectal carcinoma ending less
             than or equal to 12 months prior to the diagnosis of metastatic cancer. Prior
             radiation therapy (in the metastatic setting) may be allowed if it was completed
             greater than or equal to 4 weeks prior to enrollment and measurable lesions are
             outside the radiation portal site.

          3. Any detectable metastases in areas other than the liver.

          4. Known liver disease or other significant medical illness that would exclude the
             patient as a candidate for resection of liver metastases.

          5. Patients requiring therapeutic coumadin or heparin (for a history of pulmonary emboli
             or deep vein thrombosis [DVT]) will be excluded.

          6. Patients who have had a major surgical procedure (not including mediastinoscopy), open
             biopsy, or significant traumatic injury less than or equal to 4 weeks prior to
             beginning treatment.

          7. History of Gilbert's disease.

          8. History of hypersensitivity to active or inactive excipients of any component of
             treatment (5 fluorouracil, irinotecan, panitumumab, and/or oxaliplatin), or known
             dipyrimidine dehydrogenase (DPD) deficiency

          9. Serious cardiac arrhythmia requiring medication.

         10. Concurrent severe, intercurrent illness including, but not limited to, ongoing or
             active infection, an infection requiring IV antibiotics, or psychiatric illness/social
             situations that would limit compliance with study requirements.

         11. Patient with known diagnosis of human immunodeficiency virus (HIV), hepatitis C virus
             or acute or chronic hepatitis B infection.

         12. Mental condition that would prevent patient comprehension of the nature of, and risk
             associated with, the study.

         13. Use of any non-approved or investigational agent less than or equal to 28 days prior
             to administration of the first dose of study drug.

         14. Past or current history of neoplasm other than the entry diagnosis with the exception
             of treated non melanoma skin cancer or carcinoma in situ of the cervix, or other
             cancers cured by local therapy alone and a DFS greater than or equal to 5 years.

         15. Patients with National Cancer Institute Common Terminology Criteria for Adverse Events
             v4.0 (NCI CTCAE) Grade 2 peripheral neuropathy.

         16. Female patients who are pregnant or lactating.