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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


Phase 2
18 Years
N/A
Open (Enrolling)
Both
Colorectal Cancer

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Trial Information

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


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.


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.

Type of Study:

Interventional

Study Design:

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

overall response rate (ORR)

Outcome Description:

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.

Outcome Time Frame:

18 months

Safety Issue:

No

Principal Investigator

Johanna Bendell, MD

Investigator Role:

Study Chair

Investigator Affiliation:

Sarah Cannon Research Institute

Authority:

United States: Food and Drug Administration

Study ID:

SCRI GI 134

NCT ID:

NCT01226719

Start Date:

December 2010

Completion Date:

December 2014

Related Keywords:

  • Colorectal Cancer
  • liver-only metastatic KRAS wild-type colorectal cancer
  • Panitumumab
  • Oxaliplatin
  • Irinotecan
  • Leucovorin
  • 5-Fluorouracil
  • Colorectal Neoplasms
  • Neoplasm Metastasis

Name

Location

Florida Cancer SpecialistsFort Myers, Florida  33901
Northeast Georgia Medical CenterGainesville, Georgia  30501
Family Cancer CenterCollierville, Tennessee  38017
Hematology-Oncology Associates of Northern NJMorristown, New Jersey  07962
The Center for Cancer and Blood DisordersFort Worth, Texas  76104
Center for Cancer and Blood DisordersBethesda, Maryland  20817
Portsmouth Regional HospitalPortsmouth, New Hampshire  03802
Tennessee Oncology, PLLCClarksville, Tennessee  37043
Providence Medical GroupTerre Haute, Indiana  47802
National Capital Clinical Research ConsortiumBethesda, Maryland  20817
Chattanooga Oncology Hematology AssociatesChattanooga, Tennessee  37404
Oncology Hematology Care, IncCincinnati, Ohio  45242
NEA Baptist ClinicJonesboro, Arkansas  72401