Study of Regorafenib drug for the treatment of patients with metastatic colorectal cancer (mCRC) with any RAS or BRAF gen mutation previously treated with FOLFOXIRI (folinic acid, 5-fluorouracil, oxaliplatin and irinotecan) plus bevacizumab

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: EUCTR2014-000703-26-ES
• Lead Sponsor: Grupo de Tratamiento de los Tumores Digestivos (TTD)

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Study Start: 2014-04-01
• Last Update Posted: 13 June 2016

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: Not specified

Inclusion Criteria

1.Signing of the informed consent form.
2.The patient must be able to understand the information and state expressly his or her desire to take part in the study.
3.Age above or equal to 18 years.
4.Histologically or cytologically documented adenocarcinoma of the colon or rectum.
5.Patients with metastatic colorectal cancer (stage IV) with any RAS or BRAF mutation.
6.To have received first-line treatment with bevacizumab in combination with chemotherapy with the three drugs 5FU/LV, irinotecan and oxaliplatin (FOLFOXIRI), and
-have had radiological progression of the disease during the first-line treatment, or
-have had radiological progression of the disease within a period of less or equal to 6 months after the last dose of first-line treatment, or
-have discontinued part or all of the first-line treatment due to toxicity and have had radiological progression of the disease within a period of less or equal to 6 months after the last dose of first-line treatment.
The patient will have to have received at least one cycle of bevacizumab in combination with FOLFOXIRI + bevacizumab as part of the first-line treatment.
Patients may have received fluoropyrimidine-based adjuvant treatment with or without oxaliplatin.

7.Existence of at least one measurable unidimensional lesion using CT or MRI based on the RECIST criteria, version 1.1
8.Overall Eastern Cooperative Oncology Group (ECOG) performance less or equal to 1.
9.Patient's commitment to compliance with the oral medication throughout the duration of the study
10.Life expectancy of at least 3 months
11.Adequate bone marrow, renal and hepatic function, defined as:
a.Neutrophils above or equal to 1500/mm3
b.Platelets above or equal to 100,000/mm3
c.Haemoglobin above or equal to 9,0 g/dL
d.Serum Creatinine less or equal to 1.5 x LSN
e.Bilirubin levels less or equal to 1.5 x LSN
f.AST and ALT levels less or equal to 2.5 x ULN (if liver metastases < or equalto 5 x ULN)
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 23
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 30

Exclusion Criteria

1.Prior treatment with regorafenib.
2.Assignment prior to treatment during this study. Patients who are permanently withdrawn from participation in the study treatment will not be allowed to return to it.
3.Prior or concurrent presence of another neoplastic disease that is different in terms of tumour site and histology of the colorectal cancer in the 5 years prior to the inclusion of the patient in the study, except in situ cervical cancer, superficial bladder carcinoma [Ta (non-invasive), Tis (carcinoma in situ) and T1 (tumour invades lamina propria)] and non-melanoma skin tumours.
4.Presence or history of brain metastases or meningeal tumours.
5.Major surgery, open biopsy or traumatic injury within 28 days prior to the start of patient treatment with the study medication.
6.Extended-field radiotherapy within 4 weeks prior to inclusion or limited-field radiotherapy in the previous 2 weeks. Patients must have recovered from all treatment-related toxicities.
7.Pregnant or breastfeeding women. Women of childbearing age must use adequate contraception. Women of childbearing age must have a negative pregnancy test within 7 days prior to starting with the study medication.
8.Women of childbearing age and men who wish to take part in the study must agree to use adequate contraception from the signing of the informed consent until at least 3 months after stopping the study medication. The investigator or the person designated by him or her will ensure and advise as to the contraceptive methods that should be used.
Appropriate contraceptive methods include abstinence, oral contraceptives, transdermal patches and injections of sustained-release progestin (starting at least 4 weeks before administration of the IMP), double-barrier method: condom or female condom (diaphragm or cervical/vaginal condom) plus spermicide, intrauterine device (IUD), intrauterine system, implant or vaginal ring (in place at least 4 weeks before administration of the IMP) or male partner sterilisation (vasectomy with documentation of azoospermia) prior to inclusion of the woman in the trial if he is the woman's only sexual partner.
9.Active congestive heart failure class 2 or higher on the NYHA scale (New York Heart Association).
10.Unstable angina (angina symptoms at rest), new-onset angina (having appeared in the past 3 months) or acute myocardial infarction that has occurred in the 6 months prior to starting with the study medication.
11.Cardiac arrhythmias that require anti-arrhythmic therapy (only beta blockers and digoxin would be allowed as concomitant medication for these patients).
12.Uncontrolled hypertension (systolic blood pressure > 150 mmHg or diastolic blood pressure > 90 mmHg) despite proper medical management.
13.Patients with phaeochromocytoma.
14.Pleural effusion or ascites that cause breathing difficulties (dyspnoea of grade above or equal to 2 of the CTC).
15.Venous or arterial thromboembolism or embolic events such as cerebrovascular accidents (including transient ischaemic attacks), deep vein thrombosis or pulmonary thromboembolism that have occurred in the 6 months prior to starting with the study medication.
16.Active infection > grade 2 based on the NCI CTC, v. 4.0.
17.Human immunodeficiency virus (HIV) infection.
18.Active hepatitis B or C, or hepatitis B or C infection that requires treatment with antiviral drugs.
19.Patients with mental disorders that require medication.
20.History of organ transplants.
21.Patients with evidence or hist

Study & Design

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

Primary Outcome Measures

Name	Time	Method
Main Objective: -To assess the efficacy of single-agent regorafenib in the second-line treatment in metastatic colorectal cancer with any RAS or BRAF mutation previously treated with FOLFOXIRI plus bevacizumab in terms of progression-free survival at 6 months.;Secondary Objective: -To assess the safety and tolerability of regorafenib in the same sub-population of patients.<br>-To assess the objective response rate (according RECIST), response according other criteria disease control rate, response duration, time to response, time to disease progression, time to treatment failure, duration of stable disease and overall survival of single-agent regorafenib in second-line treatment in metastatic colorectal cancer with any RAS or BRAF mutation previously treated with FOLFOXIRI plus bevacizumab.;Primary end point(s): -Progression-free survival rate at 6 months.;Timepoint(s) of evaluation of this end point: 6 months after first treatment dose

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): -Efficacy: <br>-Objective response rate based on the RECIST criteria<br>-Disease control rate<br>-Response according other criteria<br>-Time to response<br>-Time to progression<br>-Progression-free survival<br>-Time to treatment failure<br>-Response duration<br>-Duration of stable disease<br>-Overall survival<br>Safety: <br>-Incidence and severity of AEs<br>-Changes in laboratory values<br>-Change in vital signs<br>-Incidence of dose adjustments and compliance<br>-Incidence of concomitant medication<br>-Changes in ECOG performance status over time from baseline;Timepoint(s) of evaluation of this end point: During treatment and follow-up period.