patients with RAS/B-RAF wild-type metastatic colorectal cancer MedDRA version: 21.0 Level: PT Classification code 10052360 Term: Colorectal adenocarcinoma System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: VECTIBIX - 20 MG/ML CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO 1 FLACONCINO (VETRO) 20 ML
Product Name: PANITUMUMAB
Pharmaceutical Form: Solution for infusion
INN or Proposed
Sponsors
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Written informed consent to study procedures and to molecular analyses; 2) Histologically proven diagnosis of colorectal cancer with wildtype RAS and BRAF status in certified laboratories; 3) Initially unresectable metastatic colorectal cancer not previously treated with chemotherapy for metastatic disease; 4) At least one measurable lesion according to RECIST1.1 criteria; 5) Availability of a tumor sample (primary and/or metastatic sites) for exploratory research; 6) Age = 18 years; 7) ECOG PS = 2; 8) Life expectancy of at least 12 weeks; 9) Previous adjuvant chemotherapy allowed only if more than 6 months elapsed between the end of adjuvant and first relapse; 10) Neutrophils = 1.5 x 109/L, Platelets =100 x 109/L, Hgb = 9 g/dl; 11) Total bilirubin =1.5 time the upper-normal limits (UNL) of the normal values and ASAT (SGOT) and/or ALAT (SGPT) = 2.5 x UNL (or =65 years) yes F.1.3.1 Number of subjects for this age range 36
Exclusion criteria
Exclusion criteria: 1) Previous treatment for metastatic disease; 2) Radiotherapy to any site within 4 weeks before the study; 3) Any contraindication to use Panitumumab, Irinotecan, 5-FU or folinic acid 4) Known or clinically suspected brain metastases. 5) History or evidence upon physical examination of CNS disease unless adequately treated. 6) Ascites, pleural effusion or pericardial fluid requiring drainage in last 4 weeks. 7) Diagnosis of interstitial pneumonitis or pulmonary fibrosis; 8) Active uncontrolled infections or other clinically relevant concomitant illness contraindicating chemotherapy administration or which, in the investigating physician's opinion, rules out the patient's participation in the study; 9) Clinically significant (i.e. active) cardiovascular disease for example cerebrovascular accidents (=6 months), myocardial infarction (=6 months), unstable angina, New York Heart Association (NYHA) grade II or greater congestive heart failure (CHF), serious cardiac arrhythmia requiring medication; 10) Treatment with any investigational drug within 30 days prior to enrolment; 11) Other co-existing malignancies or malignancies diagnosed within the last 5 years with the exception of localized basal and squamous cell carcinoma or cervical cancer in situ; 12) Lack of physical integrity of the gastrointestinal tract or history of acute or sub-acute intestinal occlusion or chronic inflammatory bowel disease or chronic diarrhea. 13) Disease that is deemed potentially resectable. 14) Known hypersensitivity to trial drugs or hypersensitivity to any other component of the trial drugs. 15) Any concomitant drugs contraindicated for use with the trial drugs according to the product information of the pharmaceutical companies. 16) Breastfeeding
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To investigate whether experimental intermittent treatment of Panitumumab + FOLFIRI (given until progression during treatment or cumulative toxicity) results in a Progression Free Survival on treatment (PFSOT) similar to that obtained with standard continuous treatment of Panitumumab + FOLFIRI (given until progression or cumulative toxicity).;Secondary Objective: To explore potential biomarkers of primary and secondary resistance as well as to monitor treatment activity by analyzing circulating tumor DNA (cfDNA) mutational status, using next generation sequencing (NGS), from blood samples (¿liquid biopsy¿) collected at baseline, at week 8, 16 and thereafter every 8 weeks, concomitantly with tumor assessment, and at progression of disease ¿ To explore the prognostic and predictive value as well as the potential to monitor treatment activity, of Metabolomic profiling in peripheral blood at baseline and during treatment (every 8 weeks and at progression of disease) evaluated by NMR Spectrometer (600 MHz). ¿ To explore the prognostic and predictive value of tumor DNA mutational profiling, evaluated by NGS on archived tumor samples or on newly obtained biopsies.;Primary end point(s): PFSot is defined as the time from randomization to the first objective disease progression documented in patients undergoing treatment cycle (objective disease progression during treatment free intervals are excluded) or death due to any cause, whichever occurs first.;Timepoint(s) of evaluation of this end point: 8 weeks | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): ¿ Safety and tolerability ¿ Quality of life (QoL) ¿ Overall response rate (ORR) ¿ Duration of response (DoR) ¿ Early Tumor Shrinkage (ETS) ¿ Deepness of response (DpR) ¿ Overall Survival (OS);Timepoint(s) of evaluation of this end point: 8 weeks | — |
Countries
Italy
Contacts
Public ContactSC oncologia clinica sperimentale a
ISTITUTO NAZIONALE TUMORI - IRCCS FONDAZIONE PASCALE
Outcome results
None listed