RAS wild type advanced colorectal cancer MedDRA version: 21.0 Level: PT Classification code 10052358 Term: Colorectal cancer metastatic System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Sponsors
Hellenic Cooperative Oncology Group (HeCOG)
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1.Signed and dated informed consent, and willing and able to comply with protocol requirements. 2.Histologically proven adenocarcinoma of the colon and/or rectum. 3.Metastatic disease confirmed clinically/radiologically. 4.Patients with Formalin-Fixed, Paraffin-Embedded (FFPE) tissue RAS wi ld type CRC at diagnosis, who had initial clinical benefit [complete response (CR), partial response (PR) or stable disease (SD)] during 1st line irinotecan-based or oxaliplatin-based chemotherapy in combination with cetuximab or panitumumab. 5.1st line treatment duration (FOLFIRI, FOLFOX + anti EGFR moAb, of whom at least 2/3 of cases being panitumumab) of at least 3 months. 6.2nd line therapy consisting of any chemotherapy (with or without Bevacizumab) definitely without anti-EGFR therapy of at least 2 months, followed by disease progression. 7.Eligible 3rd line regimens include FOLFIRI or Irinotecan or FOLFOX, according to standard practice and approved indications. It is required that the 3rd line regimen used will be different from the 2nd line and similar to the 1st line regimen. 8.At least one measurable or evaluable lesion as assessed by computed tomography (CT) scan or Magnetic Resonance Imaging (MRI) according to RECIST v1.1. 9.First course of treatment planned less than 1 week (7 days) after registration. 10.Age =18 years. 11.ECOG Performance status (PS) 0-2. 12.Adequate hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL. 13.Adequate renal function: serum creatinine level 50 mL/min by Cockroft/Gault formula. 14.Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase, AST, ALT =65 years) yes F.1.3.1 Number of subjects for this age range 13
Exclusion criteria
Exclusion criteria: 1.Presence of CNS metastasis unless adequately treated (e.g. ineligible in the case of non irradiated CNS metastasis, seizures not controlled with standard medical therapy). 2.Active infection (ie, body temperature =38°C due to infection). 3.Intestinal obstruction, pulmonary fibrosis or interstitial pneumonitis, renal failure, liver failure, or cerebrovascular disorder. 4.Uncontrolled diabetes. 5.Myocardial infarction, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV within the last six months. 6.Known human immunodeficiency virus (HIV) or acquired immunodeficiency syndrome (AIDS)-related illness, or hepatitis B or C. 7.Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy. 8.Other concomitant or previous malignancy, except: i/ adequately treated in-situ carcinoma of the uterine cervix, ii/ basal or squamous cell carcinoma of the skin, iii/ cancer in complete remission for >5 years. 9.Major surgery or traumatic injury within the last 28 days. 10.Pregnant or breastfeeding women. 11.Patients with known allergy to any excipients to study drugs. 12.Other serious and uncontrolled chronic non-malignant disease. 13.Known dihydropyrimidine dehydrogenase (DPD) deficiency. 14.Palliative radiation therapy within 4 weeks prior to registration. 15.Life expectancy less than 12 weeks in the opinion of the Investigator. 16.Treatment with any other investigational medicinal product within 28 days prior to study entry.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To evaluate the efficacy, in terms of overall response rate (ORR), of the addition of panitumumab rechallenge to standard 3rd-line irinotecan-based or oxaliplatin-based chemotherapy in patients with mCRC initially treated with, and benefiting from, 1st line irinotecan-based or oxaliplatin-based chemotherapy combined with an anti-EGFR moAb, followed by 2nd line chemotherapy not containing anti-EGFR agents.;Secondary Objective: 1.To evaluate the efficacy, in the subgroups of RAS status, in terms of ORR, of the addition of panitumumab rechallenge to standard 3rd-line irinotecan-based or oxaliplatin-based chemotherapy . 2.To study the survival parameters, i.e. progression free survival and overall survival,of the combination of standard 3rd-line irinotecan-based or oxaliplatin-based chemotherapy. 3.To evaluate the safety of the combination of standard 3rd-line irinotecan-based or oxaliplatin-based chemotherapy with panitumumab rechallenge. 4.To identify, in the context of translational research, tumour tissue and blood-based biomarkers with prognostic/predictive significance in patients with metastatic colorectal cancer (mCRC) treated with rechallenge panitumumab in combination with standard 3rd-line irinotecan-based or oxaliplatin-based chemotherapy. ;Primary end point(s): Overall response rate (ORR), defined as the percentage of patients having achieved complete response (CR) or partial response (PR) as the best overall tumor response according to RECIST v1.1 criteria ;Timepoint(s) of evaluation of this end point: Imaging studies will be performed at baseline and every 8 +/- 2 weeks until progression disease or initiation of another anti-tumor therapy. | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): 1.ORR by RAS status:ORR will be calculated separately for RAS mutant and wild type patients. ORR is defined as the proportion of patients with confirmed CR or PR as best overall response to treatment, based on Response Evaluation Criteria in Solid Tumors (RECIST) v. 1.1 guidelines [(relative to the total number of patients in the considered analysis population (ITT or evaluable for response)]. Tumor assessments will be performed up to progression or initiation of another anti-tumor therapy. 2.Progression Free Survival (PFS):PFS is defined as the time interval from registration to the first date of documented tumor progression or death from any cause. Patients alive that have not progressed or patients lost to follow up or patients who received other anti tumor therapy before tumor progression will be censored at the date of their last tumor assessment. Deaths occurring after initiation of subsequent anticancer therapy will be considered PFS events. 3.Overall Survival (OS):OS is defined as the time interval from registration to the date of death due to any cause. Patients who have not died or who are lost to follow-up will be censored on the last date on which they were known to be alive. Patients alive at the end of the study will be censored at this timepoint. 4.Safety:Adverse event data, clinical examination, vital signs (blood pressure, pulse and respiratory rate), body weight, ECOG PS and laboratory data (complete blood count, biochemistry profile, urinalysis and other tests as clinically indicated) will be recorded in the source documents and in the subject’s CRF. Laboratory safety will be carried out by local laboratory according to standard operating procedures. Any abnormal laboratory value will be immediately rechecked for confirmation before making a decision of permanent discontinuation of Investigational Product for the concerned patient. 5. Mutational status of KRAS and NRAS genes will be performed in formalin- fixed parafin-em | — |
Countries
Cyprus, Greece
Contacts
Public ContactClinical Trials
Hellenic Cooperative Oncology Group (HeCOG)
Outcome results
None listed