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

NCT ID: NCT01226719

Last Updated: 2015-05-27

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2010-12-31
• Study Completion Date: 2014-03-31

Brief 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.

Detailed Description

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.

Conditions

Colorectal Cancer

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

FOLFOXIRI+panitumumab regimen

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

• Panitumumab
• Oxaliplatin
• Irinotecan
• Leucovorin
• 5-Fluorouracil

Group Type: EXPERIMENTAL

Panitumumab

Intervention Type: DRUG

6 mg/kg, 60-90 minute IV infusion every 2 weeks

Oxaliplatin

Intervention Type: DRUG

85 mg/m2, 2-hour IV infusion every 2 weeks

Irinotecan

Intervention Type: DRUG

125 mg/m2, 1-hour IV infusion every 2 weeks

Leucovorin

Intervention Type: DRUG

200 mg/m2, 2-hour IV infusion every 2 weeks

5-Fluorouracil

Intervention Type: DRUG

3200 mg/m2 IV, 48-hour continuous infusion every two weeks

Interventions

Panitumumab

6 mg/kg, 60-90 minute IV infusion every 2 weeks

Intervention Type: DRUG

Oxaliplatin

85 mg/m2, 2-hour IV infusion every 2 weeks

Intervention Type: DRUG

Irinotecan

125 mg/m2, 1-hour IV infusion every 2 weeks

Intervention Type: DRUG

Leucovorin

200 mg/m2, 2-hour IV infusion every 2 weeks

Intervention Type: DRUG

5-Fluorouracil

3200 mg/m2 IV, 48-hour continuous infusion every two weeks

Intervention Type: DRUG

Other Intervention Names

Combined Modality Treatment; Combined Modality Treatment; Combined Modality Treatment; Combined Modality Treatment; Combined Modality Treatment

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.

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Amgen

INDUSTRY

Sponsor Role: collaborator

SCRI Development Innovations, LLC

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Johanna Bendell, MD

Role: STUDY_CHAIR

SCRI Development Innovations, LLC

Locations

NEA Baptist Clinic

Jonesboro, Arkansas, United States

Florida Cancer Specialists

Fort Myers, Florida, United States

Florida Hospital Cancer Institute

Orlando, Florida, United States

Florida Cancer Specialists

St. Petersburg, Florida, United States

Northeast Georgia Medical Center

Gainesville, Georgia, United States

Hope Cancer Center

Terre Haute, Indiana, United States

Providence Medical Group

Terre Haute, Indiana, United States

Center for Cancer and Blood Disorders

Bethesda, Maryland, United States

Portsmouth Regional Hospital

Portsmouth, New Hampshire, United States

Hematology-Oncology Associates of Northern NJ

Morristown, New Jersey, United States

Oncology Hematology Care, Inc

Cincinnati, Ohio, United States

Chattanooga Oncology Hematology Associates

Chattanooga, Tennessee, United States

Family Cancer Center

Collierville, Tennessee, United States

Tennessee Oncology, PLLC

Nashville, Tennessee, United States

The Center for Cancer and Blood Disorders

Fort Worth, Texas, United States

Countries

United States

References

Bendell JC, Zakari A, Peyton JD, Boccia R, Moskowitz M, Gian V, Lipman A, Waterhouse D, LoCicero R, Earwood C, Lane CM, Meluch A. 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. Oncologist. 2016 Mar;21(3):279-80. doi: 10.1634/theoncologist.2015-0439. Epub 2016 Feb 24.

Reference Type: DERIVED

PMID: 26911408 (View on PubMed)

Other Identifiers

SCRI GI 134

Identifier Type: -

Identifier Source: org_study_id