Study to evaluate the efficacy of FOLFIRI + aflibercept in patients with metastatic colorectal cancer previously treated with oxaliplatin with or without ACE polymorphisms

Phase 1

• Conditions: Metastatic colorectal cancer; MedDRA version: 19.0Level: LLTClassification code 10052362Term: Metastatic colorectal cancerSystem Organ Class: 100000004864; Therapeutic area: Diseases [C] - Cancer [C04]

• Registration Number: EUCTR2016-001508-45-ES
• Lead Sponsor: Grupo de Tratamiento de los Tumores Digestivos (TTD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2016-07-15
• Last Update Posted: 7 January 2019

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 100

Inclusion Criteria

1. Informed consent form signed and dated, and willingness and ability to accomplish the protocol requirements.
2. Histologically confirmed Adenocarcinoma of the colon and / or rectum
3. Diagnosed metastatic disease.
4. Evidence of at least one measurable lesion using one-dimensional CT or MRI according to RECIST criteria, version 1.1.
5. Patients with metastatic colorectal cancer (MCRC) that is resistant or has progressed after treatment with oxaliplatin.
6. Age = 18 years.
7. Functional status (EF) of the World Health Organization (WHO) of 0 to 2.
8. Adequate bone marrow function: neutrophils (ANC) = 1.5 x 109 / l; platelets = 100 x
109 / l; hemoglobin = 9 g / dl.
9. Adequate renal function: serum creatinine level <1.5 times the upper limit of normal (ULN).
10. Adequate liver function: serum bilirubin = 1.5 times the ULN, alkaline phosphatase (AP) <5 ULN.
11. Proteinuria <2+ (urine dipstick test) or = 1 g / 24 hours.
12. Feasibility of performing regular monitoring
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 80
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 20

Exclusion Criteria

1. Uncontrolled hypercalcemia.
2. Pre-existing permanent Neuropathy (NCI grade> 2).
3. Uncontrolled hypertension (defined as systolic blood pressure > 150 mm Hg and / or diastolic blood pressure> 100 mm Hg) or history of hypertensive crisis or hypertensive encephalopathy.
4. Concomitant antineoplastic treatment non-scheduled in the protocol (e.g., chemotherapy, targeted molecular therapy, immunotherapy).
5. Treatment with any other investigational product within 28 days prior to inclusion in the study.
6. Another serious and uncontrolled non-malignant disease
7. History or evidence of CNS metastases on physical examination, unless it is properly treated (e.g., non-irradiated CNS metastases, convulsion uncontrolled with standard medical treatment).
8. Diagnosis of Gilbert's syndrome.
9. Atropine sulfate or loperamide intolerance.
10. Diagnosis of dihydropyrimidine dehydrogenase deficiency.
11. Treatment with inducers of CYP3A4, unless it is suspended> 7 days before inclusion.
12. Any of the following conditions in the 3 months prior to the screening visit: gastrointestinal hemorrhage grade 3 - 4 (unless it is caused by tumor extirpation), peptic ulcer resistant to treatment, esophagitis or erosive gastritis, infectious or inflammatory bowel disease or diverticulitis.
13. Other concomitant or previous malignant neoplasia, except for: i / Carcinoma in situ of the uterine cervix properly treated, ii / spinocellular or basal skin cell carcinoma, iii / cancer in complete remission for> 5 years.
14. Any other non-malignant and uncontrolled serious disease, major surgery or traumatic injury in the last 28 days.
15. Pregnant or during breast-feeding period.
16. Patients with known allergy to any component of the study drugs.
17. History of myocardial infarction and / or stroke in the previous 6 months before inclusion, congestive heart failure NYHA class III and IV.
18. Intestinal obstruction.

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 efficacy of FOLFIRI + aflibercept in patients with or without ACE polymorphisms in terms of progression-free survival (PFS);Secondary Objective: Objective response rate (ORR) (based on RECIST criteria), disease control rate (DCR), time to progression (TTP), time to treatment failure (TTF) and overall survival (OS) in patients with or without ACE polymorphisms.<br>ORR, DCR, PFS, TTP, TTF and OS in patients with or without polymorphisms AGTR1 and / or according to CEA levels.<br>Safety and tolerability of FOLFIRI + aflibercept.;Primary end point(s): Progression-free survival;Timepoint(s) of evaluation of this end point: Date of the first disease progression , radiologically observed, or death (event that occurred first) , estimated period: 12 months.

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): Objective response rate (ORR);<br>Disease control rate (DCR);<br>Time to progression (TTP):<br>Time to treatment failure (TFT);<br>Overall survival (OS).;Timepoint(s) of evaluation of this end point: Objective response rate (ORR) during the study treatment period;<br>Disease control rate (DCR) during the study treatment period;<br>Time to progression (TTP): date of the first disease progression or date of the last assessment for patients who died before disease progression;<br>Time to treatment failure (TFT): date of decision to finish study treatment or date of the last disease evaluation for patient who stay on treatment at the end of study. <br>Overall survival (OS): date of death for any reason or last contact date with patient at the end of the study