Phase II Trial in Metastatic Colorectal Cancer With FOLFIRI Plus Aflibercept as First Line Treatment (MINOAS)

Phase 1

• Conditions: Metastatic colorectal cancer; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2014-001422-16-GR
• Lead Sponsor: Hellenic Oncology Research Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2015-09-21
• Last Update Posted: 12 February 2018

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: 50

Inclusion Criteria

• Patients with histologically documented adenocarcinomas of colon or rectum with unresectable metastatic disease.
• No prior treatment for metastatic disease
• Metastatic liver disease assessable with diffusion-weighted MR Imaging.
• No previous treatment with bevacizumab or Cetuximab or Panitumumab.
• Patients may have receive fluoropyrimidines with or without oxaliplatin as adjuvant treatment, if they have progressed > 12 months after the end of the last cycle of the adjuvant treatment
• Performance Status (ECOG) 0-2
• Life expectancy = 3 months.
• Effective contraception for both male and female subjects if the risk of conception exists.
• Adequate laboratory parameters: Absolute neutrophils count = 1.5 x 109 /L, Platelets = 100 x 109 /L, Leucocytes > 3,000/mm; Hemoglobin> 10.5g/dl, creatinine clearance = 60 ml/min, Proteinuria <2+ (dipstick urinalysis) or =1g/24hour, Magnesium = lower limit of normal, Calcium = lower limit of normal, total Bilirubin = 1.5 times the upper limit of normal; aspartate and alanine aminotransferase = 3 times of the upper normal limit in absence of liver metastases, or =5xUNL in presence of liver metastases, alkaline phosphatases < 5xULN
• All patients will have to sign written informed consent in order to participate in the study.
• Female patients must commit to using reliable and appropriate methods of contraception until at least three months after the end of study treatment (when applicable). Male patients with a partner of childbearing potential must agree to use contraception in addition to having their partner use another contraceptive method during the trial
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 50
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 50

Exclusion Criteria

•Known hypersensitivity reaction to the component of the treatment.
•Inability to underwent a diffusion-weighted MR Imaging at baseline and in predefined time points
•Subject pregnant or breast feeding, or planning to become pregnant within 6 months after the end of treatment.
•History or evidence upon physical examination of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizure not controlled with standard medical therapy),
•Concomitant protocol unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
•Treatment with any other investigational medicinal product within 28 days prior to study entry.
•Other serious and uncontrolled non-malignant disease
•Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or hypertensive encephalopathy.
•Gilbert's syndrome
•Intolerance to atropine sulfate or loperamide
•Known dihydropyrimidine dehydrogenase deficiency
•Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization
•Any of the following in 3 months prior to inclusion: grade 3-4 gastrointestinal bleeding (unless due to resected tumor), treatment resistant peptic ulcer disease, erosive esophagitis or gastritis, infectious or inflammatory bowel disease, or diverticulitis
•Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
•INR in absence of anticoagulation therapy > 1.25 or poorly controlled anti-coagulation therapy on coumadin or heparin compounds (INR >3.0)
•History of myocardial infarction and/or stroke within 6 months prior to randomization, NYHA class III and IV congestive heart failure
•History of life threatening (grade 4) venous thromboembolic events (including pulmonary embolism) within 6 months prior to registration,
•Bowel obstruction
•Legal incapacity or limited legal capacity.
•Medical or psychological condition which in the opinion of the investigator would not permit the subject to complete the study or sign meaningful informed consent.
•A second primary tumour other than non-melanoma skin cancer or in situ cervical cancer.
•History of interstitial lung disease e.g. pneumonitis or pulmonary fibrosis or evidence of interstitial lung disease on chest CT scan.

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To evaluate the objective response rates (CR and PR) of FOLFIRI plus aflibercept as 1st line treatment in patients with mCRC.;Secondary Objective: •To evaluate the progression-free survival (PFS) in patients with mCRC who achieved complete or partial response or stable disease after 1st-line treatment with FOLFIRI plus aflibercept.<br>•To assess the median overall survival in the study population<br>•To evaluate the safety of FOLFIRI plus aflibercept in patients with mCRC.<br>;Primary end point(s): To evaluate the objective response rates (CR and PR) of FOLFIRI plus aflibercept as 1st line treatment in patients with mCRC.;Timepoint(s) of evaluation of this end point: To be evaluated at the end of the study. It will also be an interim analysis of the first 30 evaluable patients will be included in the study.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): •To evaluate the progression-free survival (PFS) in patients with mCRC who achieved complete or partial response or stable disease after 1st-line treatment with FOLFIRI plus aflibercept.<br>•To assess the median overall survival in the study population<br>•To evaluate the safety of FOLFIRI plus aflibercept in patients with mCRC.;Timepoint(s) of evaluation of this end point: To be evaluated at the end of the study. It will also be an interim analysis of the first 30 evaluable patients will be included in the study.