Study to assess the efficacy and safety of treatment with FOLFIRI-aflibercept compared to initial treatment with FOLFIRI-aflibercept (for 6 cycles) followed by maintenance with 5FU-aflibercept, in an elderly population with metastatic colorectal cancer after failure of an oxaliplatin-based regime

Phase 1

• Conditions: Metastatic colorectal cancer; MedDRA version: 20.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-004076-21-ES
• Lead Sponsor: Grupo de Tratamiento de los Tumores Digestivos (TTD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2017-05-29
• Last Update Posted: 3 July 2017

Recruitment & Eligibility

• Status: Authorised-recruitment may be ongoing or finished
• Sex: All
• Target Recruitment: Not specified

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. Existence of at least one measurable unidimensional lesion using CT or MRI
based on the RECIST criteria, version 1.1
4. Patients with metastatic colorectal cancer (mCRC) that is resistant to or has
progressed after a first line oxaliplatin-containing regimen for metastatic
disease.
5. Age =70 years
6. World Health Organization (WHO) Performance status (PS) 0-2,
7. Hematological status: neutrophils (ANC) =1.5x109/L; platelets =100x109/L;
haemoglobin =9g/dL
8. Adequate renal function: serum creatinine level < 1.5 x ULN
9. Adequate liver function: serum bilirubin =1.5 x upper normal limit (ULN), alkaline phosphatase (ALP) <5xULN
10. Proteinuria <2+ (dipstick urinalysis) or =1g/24hour.
11. Regular follow-up feasible.
12. 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) no
F.1.2.1 Number of subjects for this age range
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 168

Exclusion Criteria

1. Uncontrolled hypercalcemia,
2. Pre-existing permanent neuropathy (NCI grade >2)
3. Uncontrolled hypertension (defined as systolic blood pressure >150 mmHg and/or diastolic blood pressure >100 mmHg), or history of hypertensive crisis, or
hypertensive encephalopathy,
4. Concomitant protocol 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 non-malignant disease,
7. 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),
8. Patients classified as fragile or delicate according to the following criteria:
a. Dependence in one or more activities of daily living according to the Katz
Index of Independence in Activities of Daily Living (ADL) scale (Appendix 8)
b. Three or more comorbidities when assessing the presence of the following
processes: congestive heart failure; heart valve disease; coronary artery
disease; chronic (obstructive or restrictive) pulmonary disease;
cerebrovascular disease; peripheral neuropathy, chronic kidney failure;
hypertension; diabetes; concomitant cancers; collagen vascular disease;
chronic liver disease; and disabling arthritis
c. Presence of geriatric syndromes: moderate-severe dementia; delirium in
stressful situations (urinary or respiratory tract infection, angina or drugs);
moderate-severe depression that interferes with the patient’s usual activity;
frequent falls (three or more per month); inattentiveness (who could help you
in the event of an emergency?); urinary incontinence in the absence of
stress, infection, diuretics or prostatic hyperplasia; faecal incontinence in the
absence of diarrhoea or laxatives; osteoporotic fractures of large bones or
vertebral compression fractures
9. Known Gilbert’s syndrome
10. Intolerance to atropine sulfate or loperamide
11. Known dihydropyrimidine dehydrogenase deficiency
12. Treatment with CYP3A4 inducers unless discontinued > 7 days prior to inclusion
13. 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.
14. 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,
15. Any other serious and uncontrolled non-malignant disease, major surgery or
traumatic injury within the last 28 days
16. Patients with known allergy to any excipient to study drugs,
17. History of myocardial infarction and/or stroke within 6 months prior to inclusion, NYHA class III and IV congestive heart failure
18. Bowel obstruction.
19. Less than 28 days elapsed from prior radiotherapy
20. Patients with pernicious anemia or other megaloblastic anemias due to vitamin B12 deficiency
21. Patients with severe infections

Study & Design

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