Clinical trial of combination chemotherapy with anti-angiogenic agent aflibercept in patients with advanced colorectal cancer

Phase 1

• Conditions: Metastatic colorectal cancer; MedDRA version: 16.1Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2013-002567-26-GR
• Lead Sponsor: Hellenic Cooperative Oncology Group

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-03-28
• Last Update Posted: 11 December 2017

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 73

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. No prior therapy for metastatic disease
5. Duly documented inoperable metastatic disease, ie not suitable for complete curative surgical resection,
6. At least one measurable or evaluable lesion as assessed by CT-scan or MRI (Magnetic Resonance Imaging) according to RECIST v1.1
7. Age =18 years,
8. ECOG Performance status (PS) 0-2,
9. Adequate hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L; haemoglobin =9g/dL,
10. Adequate renal function: serum creatinine level =1.5 mg/dl and Glomelular Filtration Rate>50 ml/min by Cockroft/Gault formula,
11. Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase, AST, ALT <5xULN,
12. Proteinuria <2+ (dipstick urinalysis) or =1g/24hour,
13. Regular follow-up feasible,
14. 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,
15. First course of treatment planned less than 1 week (7 days) after registration,
16. For female patients of childbearing potential, negative serum pregnancy test within 1 week (7 days) prior of starting study treatment,
17. 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 51
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 22

Exclusion Criteria

1. Exclusive presence of bone metastasis only,
2. Uncontrolled hypercalcemia,
3. 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,
4. Concomitant unplanned antitumor therapy (e.g. chemotherapy, molecular targeted therapy, immunotherapy),
5. Treatment with any other investigational medicinal product within 28 days prior to study entry,
6. Other serious and uncontrolled chronic non-malignant disease,
7. History or presence of CNS metastasis unless adequately treated (e.g. non irradiated CNS metastasis, seizures not controlled with standard medical therapy)
8. Gilbert’s syndrome,
9. Intolerance to atropine sulfate or loperamide
10. Known dihydropyrimidine dehydrogenase deficiency
11. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to randomization
12. 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.
13. 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,
14. Any other serious and uncontrolled non-malignant disease, major surgery or traumatic injury within the last 28 days
15. Pregnant or breastfeeding women,
16. Patients with known allergy to any excipients to study drugs,
17. 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,
18. Poorly controlled cardiac arrhythmias
19. Bowel obstruction
20. History of severe tumour bleeding or bleeding disorders
21. Poorly controlled anti-coagulation therapy (INR>3.0 on coumadin or heparin compounds)
22. Palliative radiation therapy within 4 weeks prior to registration.

Study & Design

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