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 Cancer Colorectal cancer (mCRC)
Conditions
Interventions
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 candidate
Sponsors
Servier Deutschland GmbH
Eligibility
Sex/Gender
All
Inclusion criteria
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
Exclusion criteria
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. Pati
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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
| Measure | Time frame |
|---|---|
| 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) | — |
Countries
Germany, United Kingdom
Contacts
Public ContactJuergen Hess
Outcome results
None listed