Study On Fatigue- And Hand-Foot Syndrome-Related Quality Of Life In Patients With Metastatic Renal Cell Carcinoma Receiving A Tyrosine Kinase Inhibitor as First-Line Treatment

Study Overview
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Brief Summary
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The purpose of this study is to know about the quality of life of patients with metastatic renal cell carcinoma who are being treated with sunitinib, pazopanib or sorafenib, and who suffer from fatigue and hand-foot syndrome, with personal inter-variability, and to explore measures that can be taken in terms of both everyday lifestyle and treatment to mitigate or cure such side effects that affect patients.

Detailed Description
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Prospective, multicentre, observational study in patients with metastatic renal cell carcinoma (mRCC) receiving a tyrosine kinase inhibitor as first-line treatment according to routine clinical practice, designed to evaluate the incidence of fatigue and hand-foot syndrome in order to determine how these affect the baseline characteristics of the patient and his/her disease (age, gender, baseline status, tumour histology, etc.) and the patient's lifestyle as such side effects develop. An exploratory analysis will be performed of measures that clinicians may adopt to improve patients' quality of life with regards to daytime naps, medication administration time, off-treatment periods, dose reductions and treatment breaks.

Official Title
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PROSPECTIVE, MULTICENTRE, OBSERVATIONAL STUDY ON FATIGUE- AND HAND-FOOT SYNDROME-RELATED QUALITY OF LIFE IN PATIENTS WITH METASTATIC RENAL CELL CARCINOMA RECEIVING A TYROSINE KINASE INHIBITOR AS FIRST-LINE TREATMENT (TROYA STUDY).

Conditions
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Metastatic Renal Cell Carcinoma

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients ≥ 18 years old and diagnosed with metastatic RCC who, in the investigator's opinion, are candidates for starting first-line treatment with a tyrosine kinase inhibitor according to routine clinical practice. Patients who have no contraindications to the treatment. Baseline ECOG ≤ 2. Patients who are able to give informed consent on their own without the need for a legal representative. Committed patients who are able to complete the quality of life questionnaires and patient diary on their own without the need for a legal representative. Exclusion Criteria: Patients who are not candidates for first-line treatment with a tyrosine kinase inhibitor. Patients who are receiving the treatment as second-line or subsequent therapy. Untreated hypothyroidism. Untreated severe anaemia. Pregnancy or breast-feeding. Myocardial infarction or cerebrovascular accidents (CVA) within the last 6 months. Severe hepatic impairment. Concomitant use of potent inhibitors or inducers that interact with hepatic cytochrome CYP3A4.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Participants Categorized According to the Napping Habits for All Participants at Baseline | In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays. | Baseline | 
| Number of Participants Categorized According to the Napping Habits for All Participants at Week 12 | In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays. | Week 12 | 
| Number of Participants Categorized According to the Napping Habits for All Participants at Week 24 | In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays. | Week 24 | 
| Number of Participants Categorized According to the Napping Habits for All Participants at Week 36 | In this outcome measure, number of participants were classified according to their habit of taking daytime rest (naps) as never, always and sometimes. Never is defined as someone who does not take any daytime nap, always is defined as someone who takes daytime naps daily and sometimes is defined as someone who takes daytime naps on weekends or on holidays. | Week 36 | 
| Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Baseline | In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes. | Baseline | 
| Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Week 12 | In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes. | Week 12 | 
| Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Week 24 | In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes. | Week 24 | 
| Number of Participants Categorized According to Association Between the Practice of Aerobic Physical Exercise and Fatigue at Week 36 | In this outcome measure, number of participants were classified according to the presence or absence of fatigue based on their habit of performing aerobic physical exercise as never, always and sometimes. | Week 36 | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Baseline | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Baseline | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 6 | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Week 6 | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 12 | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Week 12 | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 18 | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Week 18 | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 24 | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Week 24 | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 30 | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Week 30 | 
| Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) Score at Week 36 | FACIT-F was a 13-item questionnaire which assessed self-reported fatigue and its impact upon daily activities and function. Participants responded to each item on a 5-point scale based on their experience of fatigue during the past 7 days (0= not at all; 1= a little bit; 2= somewhat; 3= quite a bit; 4= very much). FACIT-F score was calculated by summing the 13 items (range 0 [not at all] to 52 [very much]); higher scores represented less fatigue and better status of participants. | Week 36 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 1 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 1 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 6 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 6 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 12 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 12 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 18 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 18 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 24 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 24 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 30 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 30 | 
| Number of Participants Classified According to Time of Taking Treatment at Week 36 | In this outcome measure, the number of participants were classified on the basis of the time of taking the oral medication - morning, afternoon or night. Morning was anytime between 7 am to 12 pm. Afternoon was anytime between 1 pm and 7 pm. Night was anytime between 8 pm to 6 am. Participants who did not take medication were also classified. | Week 36 | 
| Number of Participants Categorized According to Number of Changes to Dose Per Treatment Cycle During 9 Months of Follow-up | In this outcome measure, number of participants were classified according to the number of changes to dose that is (i.e). 0, 1 or 2 occurred per treatment cycle during 9 months of follow-up. | During 9 months | 
| Number of Participants Categorized According to Number of Interruptions to Dose Occurred in Each Treatment Cycle During 9 Months of Follow-up | In this outcome measure, number of participants were classified according to the number of interruptions to dose i.e. 0, 1, 2, 3 or 4 occurred in each treatment cycle during 9 months follow-up. | During 9 months | 
| Number of Participants With Best Response Per Response Evaluation Criteria for Solid Tumours Version 1.1. (RECIST v1.1) | Best response was recorded from start of treatment with TKI until best complete response (CR), partial response (PR), stable disease (SD) or disease progression (DP) was achieved. RECIST v1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (target lesions [TLs]) or non-target lesions (non-TLs) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all TLs, taking as reference baseline sum of diameters; c) DP: >=20% increase in sum of diameter of all TLs, taking as reference the smallest sum on study (including baseline measurement), sum must also be absolute increase of >=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion; d) SD: neither sufficient shrinkage to qualify for PR nor sufficient increase in lesions to qualify for PD referring smallest sum diameter. Participant whose best response was not determined were classified as Undetermined. | From start of treatment with TKI until first documented best response of CR, PR, SD or DP (approximately maximum up to 3.8 years) | 
| Mean Duration of Treatment | In this outcome measure, the mean duration of treatment was calculated and reported below. | From start of treatment till end of treatment (approximately maximum up to 3.8 years) | 
| Time to Treatment Failure (TTF) After Initiation of Tyrosine Kinase Inhibitor Therapy | TTF was defined as the time from the start of treatment with a TKI to tumour progression, treatment discontinuation for any reason or death from any cause. Participants who did not had the event were censored on the date of their final follow-up. Per RECIST 1.1, tumour progression: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum on study (including baseline measurement) of diameter of all target lesions, sum must also demonstrate an absolute increase of >=5 mm. Unequivocal progression of existing non target lesions. Appearance of at least 1 new lesion. | From start of treatment with a TKI to tumour progression, treatment discontinuation for any reason or death from any cause or till follow-up in case of no event (approximately maximum up to 3.8 years) | 
| Number of Participants Categorized According to Number of Treatment Cycles Received | In this outcome measure, number of participants were classified according to number of treatment cycles received. | From start of treatment till end of treatment (approximately maximum up to 3.8 years) | 
| Progression-Free Survival (PFS) | PFS was defined as the time from the start of treatment with a TKI to tumour progression or death for any reason. Participants who, did not had the event were censored on the date of their final follow-up. Per RECIST v1.1, tumour progression: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum on study (including baseline measurement) of diameter of all target lesions, sum must also demonstrate an absolute increase of >=5 mm. Unequivocal progression of existing non target lesions. Appearance of at least 1 new lesion. | From start of treatment with a TKI to tumour progression or death for any reason or till follow-up in case of no event (approximately maximum up to 3.8 years) | 
| Objective Response Rate (ORR) | ORR was defined as the percentage of participants who achieved CR or PR. Per RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (target lesions or non-target lesions) must have reduction in short axis to <10 mm; normalization of tumor marker level for non-TLs; b) PR: >=30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters. | From start of treatment with TKI until first documented CR or PR (approximately maximum up to 3.8 years) | 
| Duration of Response (DOR) | In participants who achieved CR or PR, DOR was defined as the duration from the documentation date of CR or PR to the first day when DP was observed. Per RECIST V1.1, a) CR: disappearance of all lesions; any pathological lymph nodes (target lesions or non-target lesions must have reduction in short axis to <10 mm; normalization of tumor marker level for non-target lesions; b) PR: >=30% decrease in sum of diameter of all target lesions, taking as reference baseline sum of diameters; c) DP: >=20% increase in sum of diameter of all measured target lesions, taking as reference smallest sum on study (including baseline measurement), sum must also demonstrate an absolute increase of >=5 mm. Unequivocal progression of existing non TLs. Appearance of at least 1 new lesion. | From day of documented CR or PR to the first day that DP was observed (approximately maximum up to 3.8 years) | 
| Number of Participants With Fatigue Event Graded Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with fatigue event were classified into following: CTCAE grade 1 to 2 and CTCAE grade 3 to 4. | During 9 months | 
| Number of Participants With Hand Foot Syndrome Event Graded Per Common Terminology Criteria for Adverse Events (CTCAE) Version 4.0 | An adverse event (AE) was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with hand foot syndrome event were classified into following: CTCAE grade 1 to 2 and CTCAE grade 3 to 4. | During 9 months | 
| Number of Participants With Palmar-Plantar Erythrodysaesthesia (HFS) Event Graded Per CTCAE Version 4.0 at Week 12 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with HFS event graded per CTCAE version 4.0 at Week 12 are reported. | Week 12 | 
| Number of Participants With Palmar-Plantar Erythrodysaesthesia (HFS) Event Graded Per CTCAE Version 4.0 at Week 24 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with HFS event graded per CTCAE version 4.0 at Week 24 are reported. | Week 24 | 
| Number of Participants With Palmar-Plantar Erythrodysaesthesia (HFS) Event Graded Per CTCAE Version 4.0 at Week 36 | AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per CTCAE version 4, Grade 1= mild AE; Grade 2= moderate AE; Grade 3= severe AE; Grade 4= life-threatening or disabling AE; Grade 5= death related to an AE. In this outcome measure number of participants with HFS event graded per CTCAE version 4.0 at Week 36 are reported. | Week 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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metastatic renal cell carcinoma