Clinical Trial of Combination Chemotherapy With Aflibercept in Patients With Advanced Colorectal Cancer

• Status: Completed
• Trial end date: 2017-09-25
• Target enrollment: 0
• Participant gender: All

Summary

The AMALTHEA (Aflibercept MAintenance after first-Line THErapy with FOLFIRI+Aflibercept in metastatic colorectal cancer patients) trial is an investigator-initiated, single arm, open-label, phase II study. Patients with histologically proven metastatic colorectal carcinoma will be treated with a combination of FOLFIRI and aflibercept for 6 months. Both Kirsten rat sarcoma viral oncogene homolog (KRAS) wild type (wt) and mutant (mut) patients wil be enrolled. In the absence of Progressive Disease (PD) after 6 months of the combination of chemotherapy and aflibercept, the patient will be treated with a maintenance therapy with aflibercept alone until PD or unacceptable toxicity, investigator's decision or patient's refusal of further treatment or death, whichever comes first.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Hellenic Cooperative Oncology Group
• Collaborator: Sanofi
• Treatments: Aflibercept; Fluorouracil; Folic Acid; Irinotecan; Leucovorin; Levoleucovorin

Criteria

Inclusion Criteria

• Histologically proven adenocarcinoma of the colon and/or rectum

• Metastatic disease confirmed clinically/radiologically

• Signed written informed consent

• No prior therapy for metastatic disease

• Duly documented inoperable metastatic disease, ie not suitable for complete curative surgical resection

• At least one measurable or evaluable lesion as assessed by Computed Tomography (CT) scan or MRI (Magnetic Resonance Imaging) according to Response Evaluation Criteria In Solid Tumors (RECIST) v1.1

• Age ≥18 years

• Eastern Cooperative Oncology Group (ECOG) Performance status (PS) 0-2

• Adequate hematological status:

• neutrophils (ANC) ≥1.5x109/L

• platelets ≥100x109/L

• haemoglobin ≥9g/dL

• Adequate renal function: serum creatinine level <1.5 mg/dl and Glomerular Filtration Rate>50 ml/min by Cockroft/Gault formula

• Adequate liver function:

• serum bilirubin ≤1.5 x upper normal limit (ULN)

• alkaline phosphatase

• aspartate aminotransferase (AST)

• alanine aminotransferase (ALT) < 5 x ULN

• Proteinuria <2+ (dipstick urinalysis) or ≤1g/24hour

• Regular follow-up feasible

• Baseline evaluations performed before registration: clinical and blood evaluations no more than 2 weeks (14 days) prior to registration, tumor assessment (chest X-ray, CT-scan or MRI, evaluation of non-measurable lesions) no more than 3 weeks (21 days) prior to registration

• First course of treatment planned less than 1 week (7 days) after registration

• For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment

• 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.

Exclusion Criteria

• Exclusive presence of bone metastasis only

• Uncontrolled hypercalcemia

• Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg despite medical therapy), or history of hypertensive crisis, or hypertensive encephalopathy

• Concomitant 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 chronic disease

• History or presence of Central Nervous System (CNS) metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizures not controlled with standard medical therapy)

• Gilbert's syndrome

• Intolerance to atropine sulfate or loperamide

• Known dihydropyrimidine dehydrogenase deficiency

• Treatment with Cytochrome P450 3A4 (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

• Other concomitant or previous malignancy, except:

• adequately treated in-situ carcinoma of the uterine cervix

• basal or squamous cell carcinoma of the skin

• cancer in complete remission for >5 years

• Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days

• Pregnant or breastfeeding women

• Patients with known allergy to any excipients to study drugs

• History of myocardial infarction and/or stroke or other arterial thrombotic events or pulmonary embolism or unstable angina pectoris within 6 months prior to registration

• Poorly controlled cardiac arrhythmias

• Bowel obstruction

• History of severe tumour bleeding or bleeding disorders

• Poorly controlled anti-coagulation therapy (INR>3.0 on coumadin or heparin compounds)

• Palliative radiation therapy within 4 weeks prior to registration