FOLFOXIRI Plus Panitumumab Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only

This study is ongoing, but not recruiting participants.
Sponsor:
Collaborator:
Amgen
Information provided by (Responsible Party):
SCRI Development Innovations, LLC
ClinicalTrials.gov Identifier:
NCT01226719
First received: October 15, 2010
Last updated: August 5, 2014
Last verified: August 2014

October 15, 2010
August 5, 2014
December 2010
December 2014   (final data collection date for primary outcome measure)
overall response rate (ORR) [ Time Frame: 18 months ] [ Designated as safety issue: No ]
To determine the overall response rate (ORR) (ORR = complete + partial response rate) of the combination of FOLFOXIRI plus panitumumab as first-line treatment of patients with liver-only metastatic KRAS wild-type colorectal cancer.
Same as current
Complete list of historical versions of study NCT01226719 on ClinicalTrials.gov Archive Site
  • R0 resection [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To determine the rate of R0 resection for patients treated with this regimen.
  • Progression-free and overall survival [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To determine the progression-free and overall survival for patients treated with this regimen
  • Patient Adverse Event [ Time Frame: 18 months ] [ Designated as safety issue: No ]
    To determine any serious adverse events produced by the drug combination regimen.
Same as current
Not Provided
Not Provided
 
FOLFOXIRI Plus Panitumumab Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only
A Phase II Study of FOLFOXIRI Plus Panitumumab Followed by Evaluation for Resection, in Patients With Metastatic KRAS Wild-Type Colorectal Cancer With Liver Metastases Only

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.

Further data has emerged showing a consistent lack of efficacy using EGFR inhibitor panitumumab in combination with chemotherapy in the treatment of patients with KRAS mutant colorectal cancer. For patients with liver-only metastatic colorectal cancer, improvement in response rates with newer chemotherapy regimens has led to a larger percentage of patients eligible for surgical resection. Treatment with FOLFOXIRI improves response rates when compared to FOLFIRI. Similarly, the addition of an EGFR inhibitor improves the response rate of FOLFIRI in patients with wild-type KRAS. In this trial, we will attempt to maximize the response rate and the surgical resection rate by using FOLFOXIRI and panitumumab.

Interventional
Phase 2
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Colorectal Cancer
  • Drug: Panitumumab
    6 mg/kg, 60-90 minute IV infusion every 2 weeks
    Other Name: Combined Modality Treatment
  • Drug: Oxaliplatin
    85 mg/m2, 2-hour IV infusion every 2 weeks
    Other Name: Combined Modality Treatment
  • Drug: Irinotecan
    125 mg/m2, 1-hour IV infusion every 2 weeks
    Other Name: Combined Modality Treatment
  • Drug: Leucovorin
    200 mg/m2, 2-hour IV infusion every 2 weeks
    Other Name: Combined Modality Treatment
  • Drug: 5-Fluorouracil
    3200 mg/m2 IV, 48-hour continuous infusion every two weeks
    Other Name: Combined Modality Treatment
Experimental: FOLFOXIRI+panitumumab regimen

All patients will receive the FOLFOXIRI/panitumumab regimen, with drugs administered in the following order:

  • Panitumumab
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • 5-Fluorouracil
Interventions:
  • Drug: Panitumumab
  • Drug: Oxaliplatin
  • Drug: Irinotecan
  • Drug: Leucovorin
  • Drug: 5-Fluorouracil
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Active, not recruiting
15
June 2015
December 2014   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
United States
 
NCT01226719
SCRI GI 134
No
SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
Amgen
Study Chair: Johanna Bendell, MD SCRI Development Innovations, LLC
SCRI Development Innovations, LLC
August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP