An Observational Study, Called RegoFlex EU, to Learn More About the Use of Stivarga at Reduced Doses as Recommended (Flexible Dosing) to Treat People With Metastatic Colorectal Cancer in Real World Settings in Europe (RegoFlex EU)

RegoFlex EU/Real World Evidence on Stivarga Flexible Dosing in Patients With Metastatic Colorectal Cancer in Europe

This is an observational study in which data from patients with metastatic colorectal cancer in three European countries who received STIVARGA® (regorafenib), are collected. In observational studies, only observations are made without specified advice or interventions.

Metastatic colorectal cancer (mCRC) is a cancer that starts in the large bowel or the rectum (the lowest part of the gut) and has spread to other parts of the body. Regorafenib is an anti-cancer drug that blocks several proteins called enzymes, which are involved in the development and growth of cancer. A wide range of such enzymes called tyrosine kinases are targeted.

In 2013, regorafenib was approved in Europe for doctors to prescribe to people with mCRC who have previously been treated or cannot receive other available treatments. It is known that doctors may change/reduce the amount (the dose) of regorafenib they give (flexible dosing), so that the patients better tolerate the treatment. However, little information is available on the doses of regorafenib given in France, Italy, and Belgium in usual practice.

In this study researchers want to learn more about how and in which amount regorafenib is usually given to patients with mCRC in France, Italy, and Belgium:

• at the beginning
• during, and
• at the end of the regorafenib therapy.

In addition, the study team will collect data about/if:

• the treatment duration at each treatment dose of regorafenib,
• the number of people who received reduced initial dosing of regorafenib in real word settings in France, Italy, and Belgium,
• reduced (flexible) initial dosing of regorafenib allows patients to stay longer on treatment.

To answer these questions, the researchers will look back at cases that have already happened when the study begins. The data will be collected through an online case report form. The doctors will provide case histories of mCRC patients who started regorafenib treatment in most recent 3 years and 4 months (from January 1, 2019 to Apr 30, 2022) or up until 3 months prior to the date of data collection.

Besides this data collection, no further tests or examinations are planned in this study.

There are no required visits or tests in this study.

Study Overview

• Status: Completed
• Conditions: Metastatic Colorectal Cancer
• Intervention / Treatment: Other: Retrospective patient chart review

• Study Type: Observational
• Enrollment (Actual): 300

Contacts and Locations

Study Locations

• United States
  • New Jersey
    • Whippany, New Jersey, United States, 07981
      • Many locations

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients with mCRC in France, Italy and Belgium and initiated regorafenib therapy between January 1, 2019 and December 31, 2021

Description

Inclusion Criteria:

• Patients with a histopathological or cytological diagnosis of colorectal cancer and metastatic disease (stages IVA, IVB, or IVC)
• Patients must have initiated regorafenib as monotherapy, regardless of line of therapy, from January 1, 2019 to December 31, 2021 (or up until 3 months prior to date of data collection, whichever occurs latest)
• Aged ≥18 years at index date

Exclusion Criteria:

• Patients with regorafenib treatment prior to January 1, 2019
• Patients who have participated in a clinical trial

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Retrospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Physicians treating patients with mCRC; Physicians provide case histories of mCRC patients	Other: Retrospective patient chart review; Retrospective patient chart review to be completed by mCRC-treating physicians. Data is collected through an online case report form (CRF); physicians provide case histories of mCRC patients who initiated regorafenib treatment in most recent 3 years (2019-2021).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Proportion of patients initiating a flexible regorafenib dose (40, 80, or 120 mg) versus 160 mg		Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Dose at treatment end (last prescribed regorafenib dose): 40, 80, 120, or 160 mg		Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Average dose intensity at first and subsequent cycles	The sum of dose strength (mg) will be divided by the days on therapy in each cycle.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Time to first dose change	Time to first dose change: time (months) from date of initial regorafenib dose to 1st dose increase/decrease among patients initiating a flexible regorafenib dose (40, 80, or 120 mg)	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Time to first full dose of 160 mg	Time to 1st full dose of 160 mg: time (months) from date of initial regorafenib dose to 1st full dose of 160 mg during the treatment history among patients with 40, 80, or 120 mg initial dose, overall and by initial dose.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Number of cycles received		Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Proportion of patients initiating 1, 2, 3, or more cycles	The label recommended regorafenib treatment cycle is 28 days.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Duration of treatment (DoT)	Duration of treatment: time (months) from date of initial regorafenib dose to date of last dose prior to a >2-week gap during the follow up period.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Time to discontinuation (TTD)	Time to discontinuation: time (months) from date of initial regorafenib dose to date of discontinuation (as indicated by CRF)	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Proportion of patients with reasons for discontinuation	Reasons for discontinuation includes: distant progression/relapse, local progression/relapse, patient choice to discontinue therapy, poor performance status, side effects, new primary malignancy, death, lost to follow up, coronavirus disease 2019 (COVID-19)-related and other.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Descriptive summary of demographics characteristics	Demographic characteristics includes: age, sex, index year (calendar year of regorafenib treatment initiation date), race, alive or deceased at time of data collection, primary cause of death (for deceased patients only).	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Stage of disease	Stage of disease includes: Stage IVA; Stage IVB and Stage IVC	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Eastern Cooperative Oncology Group (ECOG) performance status	ECOG scale scores are: 0, 1, 2, 3, 4 and Unknow. The higher score means worse performance status.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Primary tumor status	Primary tumor status includes: Local recurrence; Resected and Unresected	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Number of metastatic	Number of metastatic includes: 1, 2 and ≥3	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Site of metastasis	Site of metastasis includes: Bone, Liver, Lung, Lymph node, Peritoneum and Other.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of K-RAS mutation status and N-RAS mutation status	K-RAS mutation status and N-RAS mutation status includes: Wild type, Mutated and Unknown.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Line of therapy (LOT) for regorafenib	Line of therapy (LOT) for regorafenib includes: 2nd, 3rd, 4th and 5th or higher.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Prior adjuvant treatment	Prior adjuvant treatment includes: No and Yes.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Treatments prior to index date, overall and by LOT	Treatments includes: Fluorouracil, Capecitabine, Irinotecan, Leucovorin, Mitomycin, Oxaliplatin, Anti-EGFR monoclonal antibody snf Anti-VEGF monoclonal antibody.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)
Descriptive summary of Pre-existing comorbidities	Pre-existing comorbidities: Asthma, Atrial fibrillation, Auto-immune disease, Cardiac dysfunction, Chronic obstructive pulmonary disease, COVID-19, Diabetes, Hepatitis C, AIDS/HIV, Human papillomavirus, Liver dysfunction, Parkinson's, Peripheral neuropathy, Renal dysfunction, Thrombocytopenia, Venous thromboembolism, Other and None.	Retrospective analysis from 01-Jan-2019 up to 30-Apr-2022 (or up until 3 months prior to date of data collection, whichever occurs latest)

Collaborators and Investigators

• Sponsor: Bayer

Publications and helpful links

Helpful Links

• Click here to find information for studies related to Bayer products. To find this study enter the NCT number or Bayer Study ID in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): August 15, 2022
• Primary Completion (Actual): January 15, 2023
• Study Completion (Actual): January 15, 2023

Study Registration Dates

• First Submitted: August 26, 2022
• First Submitted That Met QC Criteria: September 19, 2022
• First Posted (Actual): September 22, 2022

Study Record Updates

• Last Update Posted (Estimate): January 26, 2023
• Last Update Submitted That Met QC Criteria: January 24, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Neoplasms by Site; Gastrointestinal Neoplasms; Digestive System Neoplasms; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Intestinal Neoplasms; Rectal Diseases; Colorectal Neoplasms
• Other Study ID Numbers: 22124

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

IPD Plan Description

Availability of this study's data will later be determined according to Bayer's commitment to the EFPIA/PhRMA "Principles for responsible clinical trial data sharing". This pertains to scope, timepoint and process of data access.

As such, Bayer commits to sharing upon request from qualified researchers patient-level clinical trial data, study-level clinical trial data, and protocols from clinical trials in patients for medicines and indications approved in the US and EU as necessary for conducting legitimate research. This applies to data on new medicines and indications that have been approved by the EU and US regulatory agencies on or after January 01, 2014.

Interested researchers can use www.clinicalstudydatarequest.com to request access to anonymized patient-level data and supporting documents from clinical studies to conduct research. Information on the Bayer criteria for listing studies and other relevant information is provided in the Study sponsors section of the portal.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No