metastatic colorectal cancer MedDRA version: 20.0 Level: LLT Classification code 10052362 Term: Metastatic colorectal cancer System Organ Class: 100000004864
Conditions
Interventions
Trade Name: Vectibix 20mgr/ml concentrate for solution for infusion
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: PANITUMUMAB
CAS Number: 339177-26-3
Other descriptive name: Vectibix
Sponsors
Grupo de Tratamiento de los Tumores Digestivos (TTD)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1)Man or woman at least 18 years old. 2)Capable of understand, sign and date an informed consent approved by an IEC. 3)Histologically confirmed adenocarcinoma of the left colon or rectum (originate in the splenic flexure, descending colon, sigmoid colon, or rectum) in patients with unresectable (not amenable to radical surgery of metastases at the study inclusion) metastatic (M1) disease. 4)Patients who had wild-type RAS status confirmed as per standard of care according to international guidelines prior to first-line initiation. *RAS analysis should include at least KRAS exons 2, 3 and 4 (codons 12, 13, 59, 61, 117 and 146) and NRAS exons 2, 3 and 4 (codons 12, 13, 59, 61 and 117). 5)At least one unidimensionally measurable lesion per RECIST criteria (version 1.1). 6)ECOG performance status =65 years) yes F.1.3.1 Number of subjects for this age range 185
Exclusion criteria
Exclusion criteria: 1)History of prior or concurrent central nervous system metastases. 2)History of another primary cancer, except: curatively treated in situ cervical cancer, or curatively resected non-melanoma skin cancer, or other primary solid tumour curatively treated with no known active disease present and no treatment administered for = 5 years before randomization. 3)Prior chemotherapy or other systemic anticancer therapy for treatment of metastatic colorectal carcinoma. 4)Prior adjuvant chemotherapy for colorectal cancer (stage I, II or III) terminated less than 6 month before metastatic disease was diagnosed. 5)Unresolved toxicities of a previous systemic treatment that, in the opinion of the Investigator, cause the patient unfit for inclusion. 6)Prior use (as monotherapy or adjuvant treatment) of anti-EGFR antibody therapy (e.g. cetuximab), anti-VEGF or small molecule EGFR inhibitors (e.g. erlotinib). 7)Prior hormonal therapy, immunotherapy or approved or experimental antibody/proteins = 30 days before inclusion. 8)Significant cardiovascular disease including unstable angina or myocardial infarction within 12 months before initiating study treatment or a history of ventricular arrhythmia. 9)Uncontrolled hypertension. 10)History of interstitial pneumonitis or pulmonary fibrosis or evidence of interstitial pneumonitis or pulmonary fibrosis on baseline chest computerised tomography (CT). 11)Treatment for systemic infection within 14 days before the start of study treatment. 12)Acute or subacute intestinal occlusion and/or active inflammatory bowel disease or other bowel disease that causes chronic diarrhoea (defined as grade = 2 diarrhoea according to NCI-CTCAE version 4.03). 13)Clinically significant peripheral sensory neuropathy. 14)Evidence of previous acute hypersensitivity reaction, of any grade, to any component of the treatment. 15)History of Gilbert disease or known dihydropyrimidine deficiency syndrome. 16)Recent (within 6 months before the start of study treatment) gastroduodenal ulcer to be active or uncontrolled. 17)Recent (within 6 months before the start of study treatment) pulmonary embolism, deep vein thrombosis, or other significant venous event. 18)Pre-existing bleeding diathesis and/or coagulopathy with exception of well-controlled anticoagulation therapy (within 6 months before the start of study treatment) 19)Recent (within 4 weeks prior to inclusion study) major surgical procedure, open biopsy, or significant traumatic injury not yet recovered from prior major surgery 20)History of any disease that may increase the risks associated with study participation or may interfere with the interpretation of study results. 21)Known positive test for human immunodeficiency virus infection, hepatitis C virus, and chronic active hepatitis B infection. 22)Any disorder that compromises the patient’s ability to provide written informed consent and/or comply with study procedures. 23)Any investigational agent within 30 days prior to inclusion. 24)Pregnant or breastfeeding woman. 25)Surgery (excluding diagnostic biopsy or placement of a central venous catheter) and/or radiotherapy within 28 days prior to inclusion in the study. 26)Male or female of childbearing age who do not agree with taking adequate contraceptive precautions, i.e. use contraception double barrier (e.g. diaphragm plus condoms) or abstinence during the course of the study and for 6 months after the last administration of study drug for women and 1 month for men. 27)The
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the progression free survival rate (PFSR) at 35 months of FOLFOX + panitumumab followed by FOLFIRI + bevacizumab (Sequence 1) versus FOLFOX + bevacizumab followed by FOLFIRI + panitumumab (Sequence 2) in patients with wild-type RAS, primary left-sided, mCRC.;Secondary Objective: To compare the overall survival rate at 35 months, the overall survival, total progression-free survival from randomization to second progression or death. To determine PFS in first-line and second-line treatment in each Sequence arm, time to first-line treatment failure and to second-line treatment failure in each Sequence arm. To evaluate the objective response rate in first and in second-line treatment in each Sequence arm. To determine the proportion of patients with Early Tumour in first and in second-line treatment. To evaluate Depth of Response in first and in second-line treatment in each Sequence arm, the disease control rate and the duration of disease control in first and in second-line treatment. To assess the duration of response in first and in second-line treatment in each Sequence arm, the time to response in first-line treatment and in second-line treatment in each Sequence arm, the safety and tolerability of both Sequence arms as first and as second line treatment.;Primary end point(s): •35-month PFSR defined as the number of patients, who at 35 months after randomization, have nothad second† or first†† disease progression nor died (due to any cause), over the total number of evaluable patients. † In patients who have initiated the second line-treatment after a first progression †† In patients who have not initiated the second line-treatment because a first disease progression has not been observed or patients who for medical reason have initiated the second line-treatment without a first progression;Timepoint(s) of evaluation of this end point: 72 months | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 35-month OSR defined as the number of patients who at 35 months after randomization have not died over the total number of evaluable patients. OS defined as the time from randomization to the date of death (due to any cause), with patients alive or lost to follow-up at the analysis data cut-off date censored at their last contact date. Total PFS defined as the time from randomization to second disease progression (i.e. progression during the second-line treatment)* or death. *Total PFS will be defined as the summation of PFSs in first-line treatment and in second-line treatments. If a patient does not initiate second-line treatment, the Total PFS for that patient will be equal to the PFS in first-line treatment. PFS in first-line treatment defined as the time from randomization to disease progression or death (due to any cause) during first-line treatment. PFS in second-line treatment defined as the time from the date of second-line treatment initiation to disease progression or death (due to any cause) during second-line treatment. Time to first-line treatment failure defined as the time form randomization to disease progression, death (due to any cause) or discontinuation due to toxicity during first-line treatment. Time to second-line treatment failure defined as the time from the date of second-line treatment initiation to disease progression, death (due to any cause) or discontinuation due to toxicity during second-line treatment. Proportion of patients with an objective response (complete or partial response) per Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 criteria in first-line treatment and in second-line treatment. Proportion of patients with ETS in first-line treatment and in second-line treatment. ETS will be defined as a reduction in tumour size =30% (RECIST 1.1 criteria) at the first evaluation (i.e. week 12) DpR measured as the maximum decrease in target measurement (RECIST 1.1 criteria) during the complete cour | — |
Countries
Portugal, Spain
Contacts
Public ContactInmaculada Ruiz de Mena
Grupo de Tratamiento de los Tumores Digestivos (TTD)
Outcome results
None listed