An Observational Study Called STAR-T to Learn More About the Sequential Treatment With Regorafenib and TAS-102 in Adults With Metastatic Colorectal Cancer Under Real World Conditions (STAR-T)

(STAR-T) Sequential TreAtment With Regorafenib and Trifluridine/Tipiracil (TAS-102, With or Without Bevacizumab) in Refractory Metastatic Colorectal Cancer: Real-world Outcomes in Community Clinical Practice in the USA

This is an observational study using data that has been collected from participants who received their usual treatments.

Metastatic colorectal cancer (mCRC) is a cancer of the colon (large bowel) or the rectum (lowest part of the bowel just before the anus) that 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 growth of cancer. The combination of anti-cancer drugs trifluridine and tipiracil is called TAS-102. It prevents cancer cells from growing and multiplying.

Both regorafenib and TAS-102 are approved treatments for metastatic colorectal cancer and are available for doctors to prescribe to people with mCRC after previous lines of treatment have been unsuccessful.

Regorafenib and TAS-102 work in different ways and impact people differently. People might receive one of these drugs first and followed by the other. The best sequence for taking these drugs is still unclear.

Researchers have also found that TAS-102, when taken with another anti-cancer drug called bevacizumab, helps people live longer than when taken alone.

To better understand the impact of the sequence of taking regorafenib and TAS-102 (with or without bevacizumab), more knowledge is needed about how these work together in people with mCRC in real world settings.

The main purpose of this study is to learn more about the characteristics and impact of treatment in people with mCRC who received regorafenib and TAS-102 (with or without bevacizumab) one after the other. This information will be grouped based on their treatment sequence and age group (less or more than 65 years old).

In addition, the researchers want to learn about :

• how long participants were treated with regorafenib and TAS-102 taken one after the other in a sequential order,
• any treatment for mCRC that the participants received after the sequential treatment,
• any treatment received for a condition in which the bone marrow cannot make up enough blood cells (a common side effect of cancer treatment), during the sequential treatment,
• if and how often white blood cells that fight infection decreased during the sequential treatment,
• the number of hospital or testing facility visits that participants had during the sequential treatment, and
• how long did participants live (also called overall survival).

The participants in this study had already received regorafenib and TS-102 (with or without bevacizumab) as part of their regular care from their doctors.

The data will come from the participants' information stored in an electronic health records database called Flatiron mCRC EDM. Data collected will be from January 2015 to December 2022.

Researchers will only look at the health information from adults in the United States of America.

In this study, only available data from routine care is collected. No visits or tests will be required as part of this study.

Study Overview

• Status: Active, not recruiting
• Conditions: Metastatic Colorectal Cancer (mCRC)
• Intervention / Treatment: Drug: Regorafenib (BAY73-4506, Stivarga®); Drug: Bevacizumab; Drug: TAS-102 (trifluridine and tipiracil, Lonsurf®)

• Study Type: Observational
• Enrollment (Actual): 818

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: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients with mCRC who received sequential treatment of Regorafenib and TAS-102 (with or without Bev), and patients with mCRC who received combo use of TAS+BEV from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cut) from Flatiron CRC EDM data (v Dec 2022 or the latest version)

Description

Inclusion Criteria:

• Adult patients who had diagnosis of mCRC (≥18 years old at diagnosis of mCRC)
• Received sequential treatment of regorafenib and TAS-102 (either mono or with bevacizumab) after mCRC diagnosis, with at least one documented clinical visit on or after treatment; OR
• Patients with mCRC who received combo use of TAS+BEV, with at least one documented clinical visit on or after treatment

Exclusion Criteria:

• Patients who had a diagnosis of gastrointestinal stromal tumors (GIST) or hepatocellular carcinoma (HCC) or other primary cancers in the baseline period (i.e., 6 months prior to index date) except non-melanoma skin cancers
• Patients involved in clinical trials during the study period (as indicated by the masked therapies)

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cohort R-T; Patients with mCRC who started with regorafenib first, followed by TAS+/-Bev (Bevacizumab) without other therapies in between.	Drug: Regorafenib (BAY73-4506, Stivarga®); Oral multitargeted kinase inhibitor; Drug: Bevacizumab; VEGFR inhibitor
Cohort T-R; Patients with mCRC who started with TAS+/-Bev first, followed by regorafenib, without other therapies in between.	Drug: Bevacizumab; VEGFR inhibitor; Drug: TAS-102 (trifluridine and tipiracil, Lonsurf®); Oral cytotoxic chemotherapy
Cohort TAS+BEV; Patients with mCRC who received combo use of TAS+BEV.	Drug: Bevacizumab; VEGFR inhibitor

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort R-T or Cohort T-R: Descriptive analysis of demographic	Demographic includes age, gender, race and ethnicity, insurance.	Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Descriptive analysis of clinical characteristics	Clinical characteristics includes number and type of prior therapies patient received for mCRC, stage at initial diagnosis, performance status, histology, time since metastatic diagnosis, Line of Treatment (LOT) of index treatment	Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Descriptive analysis of biomarker Kirsten rat sarcoma 2 viral oncogene homolog (KRAS)	Biomarker B-Raf Proto-Oncogene (BRAF) and Mismatch Repair / Microsatellite instability (MMR/MSI) will be explored depending on data availability.	Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cohort R-T or Cohort T-R: Duration of sequential treatment		Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Proportion of patients receiving subsequent therapies		Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Type of subsequent therapies		Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Frequency of myelosuppression related medical interventions during sequential treatment	Myelosuppression related medical interventions [e.g., use of Granulocyte colony stimulating factors (G-CSF)]	Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Frequency and incidence rate of neutropenia during sequential treatment		Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Number of patients with health care resource utilizations during sequential treatment	Health care resource utilizations includes office/hospital visit and lab visit.	Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)
Cohort R-T or Cohort T-R: Overall survival of patients with Regorafenib followed by TAS-102 and vice versa in 3rd line treatment and 4th line treatment		Retrospective analysis period is from Jan 2015 to Sep 2022 (or 3 months prior to the latest data cutoff date)

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 ClinicalTrials.gov identifier (NCT) number or Bayer Study Identifier (ID) in the search field.

Study record dates

Study Major Dates

• Study Start (Actual): April 24, 2023
• Primary Completion (Estimated): April 1, 2024
• Study Completion (Estimated): April 1, 2024

Study Registration Dates

• First Submitted: April 21, 2023
• First Submitted That Met QC Criteria: April 21, 2023
• First Posted (Actual): May 3, 2023

Study Record Updates

• Last Update Posted (Actual): March 15, 2024
• Last Update Submitted That Met QC Criteria: March 14, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: Chemotherapy; Regorafenib; TAS-102; Colon rectal cancer; Targeted medicine
• 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; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Antiviral Agents; Antimetabolites; Antineoplastic Agents; Antineoplastic Agents, Immunological; Angiogenesis Inhibitors; Angiogenesis Modulating Agents; Growth Substances; Growth Inhibitors; Bevacizumab; Trifluridine
• Other Study ID Numbers: 22386

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.vivli.org 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 member 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