Clinical trial NCT00885885: Safety and Efficacy Study of FOLFOX4+Panitumumab vs.FOLFIRI+Panitumumab in Subjects WT KRAS Colorectal Cancer and Liver-only Metastases
Official title: An Open Label Randomized, Multi-Centre Exploratory Phase II Study 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.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Colorectal Cancer
Keywords: Colorectal Cancer
Panitumumab
FOLFOX-4
FOLFIRI
Lead sponsor: Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD)
Sponsor class: OTHER
Collaborators: name: Amgen
First posted: 2009-04-22
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: 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

Primary outcomes:
measure: Objective response rate
timeFrame: 2009-2013
Secondary outcomes:
measure: % of patients whose disease becomes resectable
timeFrame: 2009-2013
measure: Time to resection
timeFrame: 2009-2013
measure: Duration of response
timeFrame: 2009-2013
measure: Progression-free survival
timeFrame: 2009-2013
measure: Time to treatment failure
timeFrame: 2009-2013
measure: Time to disease relapse following surgery.
timeFrame: 2009-2013
measure: Adverse Events
timeFrame: 2009-2013
measure: Evaluation of molecular predictive markers for response.
timeFrame: 2009-2013
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Spanish Cooperative Group for Gastrointestinal Tumour Therapy
Study officials:
affiliation: ICO-H. Germans Trial i Pujol. Badalona. Spain
name: Albert Abad, MD, phD
role: STUDY_CHAIR
affiliation: Hospial Ramón y Cajal. Madrid. Spain
name: Alfredo Carrato, MD, phD
role: STUDY_CHAIR
References:
citation: Benavides M, Diaz-Rubio E, Carrato A, Abad A, Guillen C, Garcia-Alfonso P, Gil S, Cano MT, Safont MJ, Gravalos C, Manzano JL, Sanchez A, Alcaide J, Lopez R, Massuti B, Sastre J, Martinez E, Escudero P, Mendez M, Aranda E. Tumour location and efficacy of first-line EGFR inhibitors in KRAS/RAS wild-type metastatic colorectal cancer: retrospective analyses of two phase II randomised Spanish TTD trials. ESMO Open. 2019 Dec 1;4(6):e000599. doi: 10.1136/esmoopen-2019-000599. eCollection 2019.
citation: Carrato A, Abad A, Massuti B, Gravalos C, Escudero P, Longo-Munoz F, Manzano JL, Gomez A, Safont MJ, Gallego J, Garcia-Paredes B, Pericay C, Duenas R, Rivera F, Losa F, Valladares-Ayerbes M, Gonzalez E, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD). First-line panitumumab plus FOLFOX4 or FOLFIRI in colorectal cancer with multiple or unresectable liver metastases: A randomised, phase II trial (PLANET-TTD). Eur J Cancer. 2017 Aug;81:191-202. doi: 10.1016/j.ejca.2017.04.024. Epub 2017 Jun 19.