Metastatic colorectal cancer
Conditions
Interventions
Trade Name: Vectibix
Product Name: Vectibix
Pharmaceutical Form: Concentrate for solution for infusion
INN or Proposed INN: PANITUMUMAB
Sponsors
Grupo de Tratamiento de los Tumores Digestivos (TTD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1. Patients that have given an IEC-approved informed consent form. 2. Men or women 18 years of age or older at the time the written informed consent is obtained. 3. Histologically confirmed metastatic adenocarcinoma of the colon or rectum Wild-Type RAS (No mutation)with at least 1 measurable metastatic lesion following RECIST criteria v 1.1 and initially irresecable (non suitable for radical surgery at the inclusion time). 4. Obtention of DNA from tumor tissue blocks sent to central lab (ICO) that is amenable for highly sensitive techniques 5. Previous irinotecan based chemotherapy +/- bevacizumab for metastatic CCR during at least 6 weeks. 6. Irinotecan based chemotherapy does not need to be the most recent chemotherapy administrated. There are no restrictions on numbers of treatments lines before study inclusion. 7. Disease progression during irinotecan treatment or within 6 months after irinotecan treatment. 8. Karnofsky status ? 70% . 9. Adequate bone marrow, hepatic, renal and metabolic functions, a) Adequate bone marrow function: neutrophils ? 1.5x109/ L; platelets ? 100x109/L; hemoglobin ? 9g/dL. b) Hepatic functions as follows: total bilirubin count ? 1.5 x ULN; ALAT and ASAT ? 2.5 x ULN (? 5 x ULN in case of liver metastasis). c) Renal function: creatinine clearance > 50 ml/min (according Cockroft y Gault formulae) d) Metabolic functions: magnesium ? lower limit of normal (LIN) 10. Life expectancy ? 3 months. Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 82 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 82
Exclusion criteria
Exclusion criteria: 1. Prior malignant tumor in the last 5 years, except a history of basal cell carcinoma of the skin or pre-invasive cervical cancer. 2. Unresolved toxicities from prior systemic therapy and/or radiotherapy that , in the opinion of the investigator , does not qualify the patient for inclusion. 3. Documented or suspected central nervous system metastases. 4. Any previous antitumoral treatment (chemotherapy, hormonal therapy , radiation treatment, surgery, immunotherapy, biologic therapy) ? 28 days before study inclusion. 5. Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia. 6. Prior anti-EGFr antibody therapy (eg , Cetuximab) or treatment small molecule EGFr tyrosine kinase inhibitors (eg , Erlotinib). Subjects who discontinue their first dose of anti-EGFR therapy (Cetuximab) because of an infusion reaction may participate in this clinical trial. 7. Paraffin-embedded tissue or unstained tumor slides from primary or metastatic tumor not available or quality ADN not available for biomarker determination by highly sensitive techniques. 8. History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis. 9. Treatment for systemic infection within 14 days before study inclusion. 10. Acute or sub-acute intestinal occlusion and /or active inflammatory bowel disease or other bowel disease causing chronic diarrhoea (defined as > 4 loose stools per day). 11. History of Gilbert's syndrome or dihydropyrimidine deficiency. 12. History of any medical condition that may increase the risks associated with study participation or may interfere with the interpretation of the study results. 13. Known positive test for human immunodeficiency virus infection ,hepatitis C virus , and chronic active hepatitis B infection. 14. Subject allergic to the ingredients of the study medication or to Staphylococcus protein A. 15. Any co-morbid disease that would increase risk of toxicity. 16. Any kind of disorder that compromises the ability of the subject to give written informed consent and/or comply with the study procedures. 17. Subject who is pregnant or breast feeding. 18. Surgery (excluding diagnostic biopsy or central venous catheter placement) ? 28 days prior study inclusion. 19. Woman or man of childbearing potential not consenting to use adequate contraceptive precautions during the course of the study and for 6 months after the last study drug administration for women , and 1 month for men. 20. Subject unwilling or unable to comply with study requirements. 21. Psychological, familial , sociological , or geographical condition potentially hampering compliance with the study protocol and follow-up schedule; those conditions should be discussed with the patient before re
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: -Estimate the effect of the combination of panitumumab with Folfiri on objective response rate (TRO) defined as complete and partial response according RECIST criteria 1.1, in patients with stage IV CCRm refractory to Irinotecan based chemotherapy without any mutation associated to resistence on KRAS, PIK3Ca(exon 20), BRAF and NRAS genes detected with highly sensitive techniques (PCR Digital in Fluidigm plataform), defined as molecular ultraselected subgroup.; Secondary Objective: -Estimate TRO in patients without mutation in KRAS and NRAS analyzed with highly sensitive techniques. -Estimate and compare TRO in patients without KRAS mutations by conventional techniques but with mutations in KRAS and NRAs detected with highly sensitive techniques, in patients without RAS mutations by conventional techniques but with mutations in KRAS and NRAs detected with highly sensitive techniques and in patients without KRAS and NRAs mutations by highly sensitive techniques -Describe and compare the efficacy of the combination in terms of disease control rate, duration of response, time to response, time to progression, Progression free survival and Overall survival in mutated and no-mutated in patients described before -Explore if determination of mutations in PIK3CA, and BRAF gens by using conventional and highly sensitive techniques increases the predictive value of efficacy in mutated and no-mutated -Evaluate safety profile ;Primary end point(s): Objective response rate (TRO); Timepoint(s) of evaluation of this end point: Date in which progression or death for any cause is documented (what happens before) . | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ? Efficay: disease control rate (TCE), duration of response (DR), time to response (THR), time to progression (THP), time to treatment failure (THF), duration of stable disease (DEE), Progression free survival (SLP) and Overall survival (SG) ? Safety: Adverse events ;Timepoint(s) of evaluation of this end point: Baseline, Death or end of study (see protocol) | — |
Countries
Spain
Contacts
Public ContactInmaculada Ruiz de Mena
Grupo de Tratamiento de los Tumores Digestivos (TTD)
Outcome results
None listed