Safety and Efficacy Study of FOLFOX4+Panitumumab vs.FOLFIRI+Panitumumab in Subjects WT KRAS Colorectal Cancer and Liver-only Metastases (PLANET)

Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)

Status and phase

Completed

Phase 2

Conditions

Colorectal Cancer

Treatments

Drug: Panitumumab+FOLFIRI

Drug: Panitumumab+FOLFOX-4

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00885885

TTD-08-04

EudraCT: 2008-006766-28

Details and patient eligibility

About

The purpose of the study is to evaluate the efficacy and safety of the combination of Panitumumab with FOLFOX 4 Chemotherapy or Panitumumab with FOLFIRI Chemotherapy in Subjects with Wild- Type KRAS Colorectal Cancer and liver-only Metastases.

Enrollment

80 patients

Sex

All

Ages

18 to 75 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Man or woman > 18 years < 75 of age
Competent to comprehend, sign, and date an IEC-approved informed consent form
Histologically confirmed adenocarcinoma of the colon or rectum
Wild Type KRAS status
Metastatic colorectal carcinoma exclusively affecting only the liver, compliant with one of the following criteria
1. Number of liver metastasis ≥ 4.
2. Size of one liver metastasis > 10 cm in diameter.
3. Liver metastases technically not resectable.
At least 1 uni-dimensionally measurable lesion
Patients with the following characteristics will be included:
1. Recurrence after adjuvant treatment with 5-fluorouracil/folinic acid or capecitabine +/- radiotherapy with a disease-free interval > than 6 months after its completion; or after oxaliplatin containing adjuvant treatment with a disease-free interval > than 12 months
2. Recurrence after surgical treatment and/or radiotherapy with no adjuvant systemic treatment.
3. De novo diagnosis of the disease.
Patients with simultaneous liver metastases are eligible, if the primary tumor has been resected at least 1 month prior chemotherapy.
Prior radiotherapy is acceptable.
Patients deemed to have no major contra-indication to liver surgery from a general health perspective.
Karnofsky performance status ≥ 70%
Adequate bone marrow function: neutrophils ≥ 1.5 x109/ L; platelets ≥ 100 x109/ L;hemoglobin ≥ 9g/ dL
Hepatic and metabolic function as follows:

Total bilirubin count ≤ 1.5 x ULN and not increasing more than 25% within the last 4 weeks; ALAT and ASAT < 5 x ULN;

Renal function, calculated creatinine clearance or 24 hour creatinine clearance ≥ 50 mL/ min.
Magnesium > LLN

Exclusion criteria

Prior anti-EGFr antibody therapy (eg, cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg, erlotinib).Subjects who have experienced an infusion reaction to their first dose of anti-EGFR therapy (cetuximab) may participate in this clinical trial.
Surgery (not including diagnostic biopsy) and/or radiotherapy in the 4 weeks prior to inclusion in the study.
Metastasis on any site other than the liver, including extrahepatic lymph nodes.
Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive carcinoma of the skin.
Systemic chemotherapy, hormonal therapy, immunotherapy or experimental or approved proteins/antibodies (eg, bevacizumab) ≤ 30 days before inclusion
Unresolved toxicities from prior systemic therapy that, in the opinion of the investigator, does not qualify the patient for inclusion
Significant cardiovascular disease including unstable angina or myocardial infarction within 6 months before initiating study treatment or a history of ventricular arrhythmia
History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest CT scan
Treatment for systemic infection within 14 days before initiating study treatment
Active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day)
History of Gilbert's syndrome or dihydropyrimidine deficiency
History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results
Known positive test for human immunodeficiency virus infection, hepatitis C virus, chronic active hepatitis B infection
subject allergic to the ingredients of the study medication or to Staphylococcus protein A
Any co-morbid disease that would increase risk of toxicity
Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures
Any investigational agent within 30 days before enrolment
Must not have had a major surgical procedure within 28 days of randomization
Subject who is pregnant or breast feeding
Woman or man of childbearing potential not consenting to use adequate contraceptive precautions i.e. double barrier contraceptive methods (eg diaphragm plus condom), or abstinence during the course of the study and for 6 months after the last study drug administration for women, and 1 month for men
Subject unwilling or unable to comply with study requirements