Regorafenib as Single Agent in Patients With Metastatic Colorectal Cancer (mCRC) With Any RAS or BRAF Mutation Previously Treated With FOLFOXIRI Plus Bevacizumab

NCT02175654 | Terminated Phase 2

• 2 other identifiers: TTD-14-012014-000703-26
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is 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.

Conditions

Colorectal Neoplasms; Metastatic Disease

Keywords

metastatic colorectal cancer; RAS/BRAF mutation; Regorafenib; FOLFOXIRI; Bevacizumab

Outcome Measures

Primary Outcomes (1)

• Progression free survival rate at 6 months

  6 months

Secondary Outcomes (16)

• Objective response rate based on the Response Evaluation Criteria in Solid Tumors criteria

  36 months

• Disease control rate

  36 months

• Response according other criteria (Appendix 9)

  36 months

• Time to response

  36 months

• Progression free survival

  36 months

Other Outcomes (2)

• microRNA expression level in the Peripheral Blood

  36 months

• Biomarkers associated with cell and tumour growth and/or the mechanism of action of regorafenib and their correlation with patients' clinical progression for efficacy and safety parameters.

  36 months

Study Arms (1)

Regorafenib

EXPERIMENTAL

Regorafenib will be administered orally at the initial dosage of 160 mg per day for 3 weeks, followed by one week of rest, according to the 3/1 regimen

Drug: Regorafenib

Interventions

Regorafenib DRUG

Regorafenib

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Signing of the informed consent form.
• The patient must be able to understand the information and state expressly his or her desire to take part in the study.
• Age ≥ 18 years.
• Histologically or cytologically documented adenocarcinoma of the colon or rectum.
• Patients with metastatic colorectal cancer (stage IV) with any RAS or BRAF mutation.
• To have received first\_line treatment with bevacizumab in combination with chemotherapy with the three drugs 5FU/leucovorin (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 ≤ 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 ≤ 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.
• Existence of at least one measurable unidimensional lesion using CT or MRI based on the Response Evaluation Criteria in Solid Tumors (RECIST) criteria, version 1.1
• Overall Eastern Cooperative Oncology Group (ECOG) performance ≤1.
• Patient's commitment to compliance with the oral medication throughout the duration of the study
• Life expectancy of at least 3 months

You may not qualify if:

• Prior treatment with regorafenib.
• 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.
• Presence or history of brain metastases or meningeal tumours.
• Major surgery, open biopsy or traumatic injury within 28 days prior to the start of patient treatment with the study medication.
• 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.
• 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.
• Active congestive heart failure class 2 or higher on the New York Heart Association (NYHA) scale.
• 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.
• Cardiac arrhythmias that require anti-arrhythmic therapy (only beta blockers and digoxin would be allowed as concomitant medication for these patients).
• Uncontrolled hypertension (systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg) despite proper medical management.
• Patients with phaeochromocytoma.
• Pleural effusion or ascites that cause breathing difficulties (dyspnoea of grade ≥ 2 of the CTC).
• 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.
• Active infection \> grade 2 based on the NCI CTC, v. 4.0.
• Human immunodeficiency virus (HIV) infection.

Sponsors & Collaborators

• Spanish Cooperative Group for the Treatment of Digestive Tumours (TTD): lead
• Bayer: collaborator

Study Sites (1)

Spanish Cooperative Group for Digestive Tumour Therapy (TTD)

Madrid, 28046, Spain

Location

Related Publications (1)

• Garcia-Alfonso P, Benavides M, Falco E, Munoz A, Gomez A, Sastre J, Rivera F, Montagut C, Salgado M, Lopez-Ladron A, Lopez R, Ruiz de Mena I, Duran G, Aranda E; Spanish Cooperative Group for the Treatment of Digestive Tumors (TTD). Single-Agent Regorafenib in Metastatic Colorectal Cancer Patients with Any RAS or BRAF Mutation Previously Treated with FOLFOXIRI plus Bevacizumab (PREVIUM Trial). Oncologist. 2018 Nov;23(11):1271-e128. doi: 10.1634/theoncologist.2018-0316. Epub 2018 Aug 17.

  PMID: 30120161 DERIVED

Related Links

• Related Info

MeSH Terms

Conditions

Colorectal Neoplasms; Neoplasm Metastasis

Interventions

regorafenib

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Pilar García Alfonso, MD

  Gregorio Marañón Hospital

  STUDY CHAIR

• Manuel Benavides, MD PhD

  Regional Universitario Hospital

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 12, 2014
• First Posted: June 26, 2014
• Study Start: June 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: February 1, 2016
• Last Updated: August 1, 2017

Record last verified: 2017-07

Locations

ES (1)