Plain English Summary
Background and study aims
Worldwide, nearly 1.25 million patients are diagnosed with colorectal cancer each year. At least 50% of patients develop metastases, and most of these patients have unresectable tumours (unable to be removed). Standard treatment for these patients involves chemotherapy and monoclonal antibodies targeting vascular endothelial growth factor (VEGF the cells that stimulate formation of blood vessels). In patients with KRAS wild-type tumours (abnormal tumours), monoclonal antibodies targeting epidermal growth factor receptor (EGFR which stimulates cell growth) are also used. 5-year survival rates in patients with metastatic colorectal cancer (mCRC), representing Stage IV CRC, were reached by only about 15% of mCRC patients. Although the outcome of patients with mCRC has clearly improved during recent years with median survival now reaching more than 30 months in recent clinical trials, more treatment options are needed for patients with disease progression after fluoropyrimidine (e.g. 5-FU), irinotecan, oxaliplatin, applicable anti-VEGF agents and anti-EGFR agents or those unable to tolerate these agents. Trifluridine/tipiracil (FTD/TPI; Lonsurf®) has been authorized in the EU since April 2016 for treatment of these patients. On the basis of the severity of the tumour disease with rather limited treatment options within the context of a previously treated tumour disease in the end-of-life situation, the health-related quality of life (HRQoL) is very important to describe the impact of treatment on the patient’s functioning regarding physical health (including disease-related morbidity), social, emotional, cognitive and role aspects. Changes of HRQoL during and after treatment with FTD/TPI have not been investigated so far in clinical trials. The aim of this study is to investigate the HRQoL in patients treated with FTD/TPI and those who are treated with best-supportive-care (BSC) while being suitable for treatment with FTD/TPI according to the summary of product characteristics.
Who can participate?
Adults aged 18 and older who have colorectal cancer.
What does the study involve?
Participants who are eligible for FTD/TPI therapy are treated like mCRC cancer patients in regular medical service receiving FTD/TPI with the only exemption that these cancer patients have to fill out 2 questionnaires (in total 36 questions) concerning their quality of life at treatment baseline and at the end of each FTD/TPI treatment cycle until end-of-treatment (i.e. disease progression).
What are the possible benefits and risks of participating?
There are no direct benefits with participating. There are no risks in the assessment of health-related quality of life under FTD/TPI therapy for mCRC patients eligible for this approved treatment regimen.
Where is the study run from?
This study is being run by Servier Deutschland GmbH (Germany) and takes place in medical clinics in Germany
When is the study starting and how long is it expected to run for?
February 2017 to October 2019
Who is funding the study?
Servier Deutschland GmbH (Germany)
Who is the main contact?
Dr Juergen Hess
Trial website
Additional identifiers
EudraCT number
2017-000292-83
ClinicalTrials.gov number
Protocol/serial number
IC4-95005-183-DEU
Study information
Scientific title
Prospective, multicenter, open-label Phase IV trial of Trifluridine/Tipiracil (FTD/TPI) to evaluate the health-related quality of life in patients with metastatic colorectal cancer (mCRC)
Acronym
Tallisur
Study hypothesis
The aim of this study is to evaluate the effect of treatment with Trifluridine/Tipiracil (FTD/TPI) on health related quality of life (HRQoL) as measured by EORTC QLQ-C30 (global health status/quality of life scale).
Ethics approval
Ethics commission of the Medical Faculty of Ludwig-Maximilians University (LMU) of Munich (Germany),: 30/08/2017, ref: 17-429fed
Study design
Prospective multicenter open-label interventional phase IV trial
Primary study design
Interventional
Secondary study design
Non randomised study
Trial setting
Hospitals
Trial type
Quality of life
Patient information sheet
Not available in web format, please use the contact details to request a patient information sheet
Condition
Treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents
Intervention
Trifluridine/Tipiracil (FTD/TPI) is already approved for the treatment of adult patients with metastatic colorectal cancer (mCRC) who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents. Nevertheless, the health related quality of life (HRQoL) data of these patients are missing and therefore have to be filed subsequently to the German Federal Joint Committee (GB-A). Thus, this trial is designed to investigate the HRQoL in (i) patients treated with FTD/TPI and (ii) those who are treated with best-supportive-care (BSC) while being suitable for treatment with FTD/TPI, but it has to be the explicit and informed choice of the patient, to limit the treatment to BSC. This design of a control trial with BSC as appropriate comparative treatment was chosen according to advice by the GB-A.
Group A: Patients who receive treatment with FTD/TPI
Each treatment cycle is 28 days.
FTD/TPI (35 mg/m2/dose) is administered orally twice daily (BID) on Days 1 to 5 and Days 8 to 12 of each 28-day cycle as long as benefit is observed or until unacceptable toxicity occurs. In the case of haematological and/or non-haematological toxicities dose adjustment may be required.
Group B: Patients who receive BSC
Each observation cycle is 28 days. Close observation will be performed until occurrence of radiological or clinical progression. Close observation will also end if the patients are given any anti-tumour therapy (chemotherapy including FTD/TPI, targeted therapy, antibodies, any antihormonal tumour treatment, immunotherapy.
Intervention type
Other
Phase
Drug names
Primary outcome measures
Quality of life is measured using the questionnaires EORTC QLQ-C30 and EQ-5D-5L at day one of every treatment/observational cycle (or within 2 days before start of the respective cycle; in Group A (FTD/TPI) also obligatory before first application of FTD/TPI in respective cycle), at the end of treatment visit/end of close observation, at follow up months one, two, three, four, five, six, nine and 12. However, questioning with EORTC QLQ-30 and EQ-5D-5L for a maximum duration of one year after the date of first application of FTD/TPI (Group A) or Cycle 1 D1 of close observation (Group B - BSC) in each individual patient.
Secondary outcome measures
1. Rate of responders in the QoL analysis (measured by the EORTC QLQ-C30, global health status/quality of life scale) at every scheduled time point for EORTC QLQ-C30 separately in the time interval from two days before start of cycle 2 until the end of treatment/end of close observation, at every time point compared to the baseline score of the global health status/quality of life scale. Response will be defined as improvement (≥ 10 scores) or stabilization (> -10 and < 10 scores) compared to the baseline score of the global health status/quality of life scale at the specified time point.
2. Progression-free survival (clinical or radiological progression) [PFS]
3. Overall survival ([OS], calculated from start of treatment/close observation on study)
4. Exploratory analysis of objective response rate (ORR)
5. Type, incidence, and severity of FTD/TPI-related adverse reactions (severity
6. Evaluated according to CTCAE version 4)
7. Tumour-related symptoms and adverse events
8. Treatment duration/exposure to FTD/TPI (Group A)
Overall trial start date
02/02/2017
Overall trial end date
31/10/2019
Reason abandoned
Eligibility
Participant inclusion criteria
1. Patients had provided written informed consent prior to any procedure
2. Patients of ≥ 18 years of age at the time of signing the informed consent
3. Histologically or cytologically confirmed UICC stage IV carcinoma of colon or rectum with metastasis (metastatic colorectal cancer) with need for treatment due to progression
4. At least one measurable or non-measurable lesion as defined by RECIST version 1.131
5. Patients who have been previously treated with, or are not considered candidates for, available therapies including fluoropyrimidine-, oxaliplatin- and irinotecan-based chemotherapies, anti-VEGF agents, and anti-EGFR agents
6. Patients able to take medications orally (ie, no feeding tube)
7. mCRC patients independent from their ECOG performance status at study enrolment
8. Adequate organ function as defined by the following laboratory values obtained within 7 days prior to first administration of FTD/TPI on Day 1 of Cycle 1 (haematology and laboratory values for patients who are administered only BSC need not be obtained within 7 days prior to observation Cycle 1) a. Absolute neutrophil count of ≥ 1.5 × 109/L, b. Platelet count ≥ 75 × 109/L, c. Total serum bilirubin of ≤ 1.5 upper limit of normal (ULN), d. Aspartate aminotransferase (AST/SGOT) and alanine aminotransferase (ALT/SGPT) ≤ 3.0 × ULN; if liver function abnormalities are due to underlying liver metastasis, AST and ALT ≤ 5 × ULN e. Calculated creatinine clearance (CrCl) ≥ 30 mL/min
9. Only applicable for females who receive treatment with FTD/TPI (Group A): Females of childbearing potential (FCBPs) must have a negative pregnancy test (urine or serum) within 7 days prior to enrolment. FCBPs must agree to use highly effective contraceptive measures with a failure rate of less than 1% per year when used consistently and correctly as defined in Section 4.1 of the CTFG guidance “Recommendations related to contraception and pregnancy testing in clinical trials”. Complete sexual abstinence is acceptable as a highly effective contraceptive method only if the subject is refraining from heterosexual intercourse during the entire study treatment with FTD/TPI and up to 6 months after the discontinuation of study drug FTD/TPI and the reliability of sexual abstinence is in line with the preferred and usual lifestyle of the subject. Women using hormonal contraceptives should agree to add a barrier contraceptive method. A woman will be considered as being of childbearing potential unless she has gone through menopause for at least 1 year (i.e. minimum of one year without menses) or unless she has a history of tubal ligation, bilateral oophorectomy or hysterectomy that is clearly documented in the patient’s source documents.
10. Only applicable for males who receive treatment with FTD/TPI (Group A): Males must agree to use effective contraceptive measures or to practice complete abstinence during the study treatment with FTD/TPI and up to 6 months after the discontinuation of study drug FTD/TPI
11. Patients capable to understand the purposes and risks of the study, who are willing and able to participate in the study, who are able to understand and to fill in the questionnaire and from whom written and dated informed consent to participate in the study has been obtained
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
195 adult mCRC patients
Participant exclusion criteria
1. Patients requesting not to be treated with FTD/TPI but considering other tumour treatment (e.g. palliative radiotherapy)
2. Concurrently active malignancies other than mCRC excluding malignancies that are disease free for more than 5 years, adequately treated basal cell or squamous cell skin cancer or carcinoma-in-situ deemed cured by adequate treatment, e.g. in situ cervical, breast or prostate cancer.
3. Brain or leptomeningeal metastases not controlled through surgery or radiotherapy
4. Active infection (i.e, body temperature ≥38°C due to infection)
5. Intestinal obstruction
6. Uncontrolled diarrhea
7. Uncontrolled diabetes
8. Pulmonary fibrosis or interstitial pneumonitis
9. Renal failure with CrCl <30 ml/min
10. Hepatic failure ≥ CTCAE version 4 Grade 3
11. Cerebrovascular accident within the last 6 months
12. Myocardial infarction within the last 6 months, severe/unstable angina, symptomatic congestive heart failure New York Heart Association (NYHA) class III or IV
13. Gastrointestinal hemorrhage within last 3 months
14. Autoimmune disorders or history of organ transplantation that require immunosuppressive therapy
15. Psychiatric disease that may increase the risk associated with study participation or study drug administration, or may interfere with the generation of QoL results
16. Any other severe concomitant disease or disorder, including the presence of laboratory abnormalities, which places the subject at unacceptable risk or which could influence patient’s ability to participate in the study and his/her safety during the study or interfere with interpretation of study results
17. Treatment with any of the following within the specified time frame prior to first administration of FTD/TPI or Day 1 of observation cycle 1 (if no administration of FTD/TPI):
17.1. Major surgery within prior 4 weeks (the surgical incision should be fully healed prior to study drug administration).
17.2. Any anticancer therapy within prior 2 weeks
17.3. Extended field radiation within prior 4 weeks or limited field radiation within prior 2 weeks
18. Participation in any other clinical trial or treatment with any experimental drug or other experimental therapy within 28 days prior to first administration of FTD/TPI or Day 1 of observation cycle 1 (if no administration of FTD/TPI); participation in a non-interventional study is permitted)
19. Patients who have already received FTD/TPI
20. Unresolved non-haematological toxicity of ≥ CTCAE version 4 Grade III attributed to prior therapies excluding anemia, alopecia, skin pigmentation and platinum induced neurotoxicity
21. Hypersensitivity to trifluridine, tipiracil or any of the excipients
22. Hereditary galactose intolerance, Lapp lactase deficiency or glucose-galactose malabsorption
23. Pregnant or breast-feeding female
24. Inappropriate for entry into this study in the judgment of the investigator
25. Patient has been committed to an institution by virtue of an order issued either by the judicial or the administrative authorities
26. Patients possibly dependent from the investigator including the spouse, children and close relatives of any investigator
Recruitment start date
22/09/2017
Recruitment end date
31/10/2018
Locations
Countries of recruitment
Germany
Trial participating centre
Klinikum der Universität München
Großhadern
Medizinische Klinik III
Marchioninistr. 15
Munich
81377
Germany
Trial participating centre
Klinikum Traunstein
Hämatologie-Onkologie
Cuno-Niggl Str. 3
Traunstein
83278
Germany
Trial participating centre
Klinikum Aschaffenburg
Hämato-Onkologische Schwerpunktpraxis
Am Hasenkopf 1
Aschaffenburg
63739
Germany
Trial participating centre
Klinikum Weiden
Medizinisches Versorgungszentrum
Söllnerstr. 16
Weiden
92637
Germany
Trial participating centre
Klinikum Bogenhausen
Englschalkinger Straße 77
München
81925
Germany
Trial participating centre
Hämatologische/onkologische Tagesklinik
Ländgasse 132-135
Landshut
84028
Germany
Trial participating centre
Gesundheitszentrum St. Marien
Mariahilfbergweg 7
Amberg
92224
Germany
Trial participating centre
MediProjekt Studienzentrum
Marienstraße 90
Hannover
30171
Germany
Trial participating centre
Universitäres Krebszentrum Leipzig (UCCL)
Liebigstr. 20
04103
Leipzig
Germany
Trial participating centre
MVZ Mitte – Onkologische Schwerpunktpraxis
Johannisplatz 1
Leipzig
04103
Germany
Trial participating centre
Klinikum Mutterhaus der Borromäerinnen
Internistische Onkologie/Infektiologie
Feldstr. 16
54290
Trier
Germany
Trial participating centre
FA für Hämatologie/Onkologie
Buchforststr. 14
Köln
51103
Germany
Trial participating centre
Universitätsklinkum Aachen
Medizinische Klinik III
Pauwelsstr. 30
Aachen
52074
United Kingdom
Trial participating centre
Universitätsklinikum Gießen und Marburg
Standort Marburg
Klinik für Innere Medizin
Baldingerstraße
Marburg
35033
Germany
Trial participating centre
MVZ MediaVita Münster
Hohenzollernring 68
Münster
Münster
Germany
Trial participating centre
Klinik für Innere Medizin, Hämatologie-Onkologie und Palliativmedizin
Ev. Klinikum Bethel
Schildescher Straße 99
Bielefeld
33611
Germany
Trial participating centre
Onkologische Schwerpunktpraxis Heidelberg
Kurfürsten Anlage 34
Heidelberg
69115
Germany
Trial participating centre
Vivantes Klinikum
Hämatologie, Onkologie und Palliativmedizin
Rudower Str. 48
Berlin
12351
United Kingdom
Trial participating centre
Nordhessen Klinikum Kassel
Hämatologie, Onkologie, Immunologie
Mönchebergstr. 41-43
Kassel
34125
Germany
Sponsor information
Organisation
Servier Deutschland GmbH
Sponsor details
Elsenheimerstr. 53
Munich
80687
Germany
Sponsor type
Industry
Website
Funders
Funder type
Industry
Funder name
Servier Deutschland GmbH
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Planned publication in a high-impact peer reviewed journal. Please use the contact details to request the study protocol.
IPD sharing statement:
The current data sharing plans for the current study are unknown and will be made available at a later date.
Intention to publish date
01/03/2020
Participant level data
To be made available at a later date
Results - basic reporting
Publication summary