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Observational Study Evaluating The Efficacy And Effects On Quality Of Life Of Targeted Treatments Following TKIs In mRCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT02315755
Recruitment Status : Completed
First Posted : December 12, 2014
Results First Posted : July 26, 2019
Last Update Posted : July 26, 2019
Sponsor:
Information provided by (Responsible Party):
Pfizer

Brief Summary:

Metastatic renal cell carcinoma (mRCC) is the most common malignant tumour of the kidneys. Targeted therapies, which were recently introduced in the treatment of mRCC, have become the standard treatment in these patients. With improved survival rate and a tolerable side effect profile, Tyrosine Kinase Inhibitors (TKIs) have largely replaced conventional immunotherapies worldwide.

In Turkey, due to reimbursement conditions, cytokine (interferon alpha) treatment is the standard treatment as first-line therapy.

Therefore, the data on quality of life (QoL) from the pivotal studies with standard TKI treatment does not reflect the QoL status of patients treated with TKIs as second or third line treatment in Turkey. In this study, the clinical outcomes and the impact on quality of life of targeted treatments following TKIs will be explored. To our knowledge, since there is no similar reimbursement condition in the world placing IFN as the first line standard treatment, this will be the first study evaluating the QoL status with targeted therapies used as 3rd line treatment in mRCC patients.


Condition or disease
Renal Cell Carcinoma

  Show Detailed Description

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Study Type : Observational
Actual Enrollment : 102 participants
Observational Model: Other
Time Perspective: Prospective
Official Title: OBSERVATIONAL STUDY EVALUATING THE EFFICACY OF TARGETED TREATMENTS FOLLOWING TYROSINE KINASE INHIBITORS IN METASTATIC RENAL CELL CARCINOMA PATIENTS AND EFFECTS ON QUALITY OF LIFE: A NATIONAL, MULTICENTER STUDY
Actual Study Start Date : May 11, 2015
Actual Primary Completion Date : November 20, 2017
Actual Study Completion Date : November 20, 2017

Resource links provided by the National Library of Medicine


Group/Cohort
Study cohort
Metastatic renal cell carcinoma patients under 3rd line targeted therapy following 1st line interferon alpha and 2nd line TKI. All patients will be ≥ 18 years old and have signed the informed consent document.



Primary Outcome Measures :
  1. Progression Free Survival (PFS) [ Time Frame: From the start of disease treatment until disease progression or death due to any cause (up to a maximum of 33 months) ]
    PFS was defined as the time duration (in months) during and after the treatment of disease that a participant lived with the disease but it did not get worse or progressed. Progressive disease as per response evaluation criteria in solid tumors (RECIST) version 1.1 defined as at least a 20 percent (%) increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 millimeter (mm) in addition to the relative increase of 20%.

  2. Percentage of Participants With Overall Objective Response [ Time Frame: Baseline until the maximum of 33 months ]
    Overall objective response was defined as the percentage of participants with best confirmed response (partial response [PR], stable disease [SD] or progressive disease [PD]) recorded from the start of the study treatment until the end of treatment as assessed by RECIST version 1.1. PR defined as a 30% or more decrease in the sum of longest dimensions of the target lesions, taking as reference the baseline sum of longest dimensions. PD defined as at least a 20% increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 mm in addition to the relative increase of 20%. SD defined as neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, reference to the smallest sum diameters while on study.

  3. Functional Assessment of Cancer Therapy Kidney Symptom Index - 15 (FKSI-15) Score at Baseline [ Time Frame: Baseline (Day 1 of Month 1) ]
    FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

  4. Change From Baseline in FKSI-15 Score at Month 3 [ Time Frame: Baseline (Day 1 of Month 1), Month 3 ]
    FKSI was used to assess QoL of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

  5. Change From Baseline in FKSI-15 Score at Month 6 [ Time Frame: Baseline (Day 1 of Month 1), Month 6 ]
    FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

  6. Change From Baseline in FKSI-15 Score at Month 9 [ Time Frame: Baseline (Day 1 of Month 1), Month 9 ]
    FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

  7. Change From Baseline in FKSI-15 Score at Last Follow-up [ Time Frame: Baseline (Day 1 of Month 1), last follow-up visit (up to 33 months) ]
    FKSI was used to assess quality of life (QoL) of the participants and consisted of 15 items (lack of energy, side effects, pain, losing weight, bone pain, fatigue, enjoying life, short of breath, worsened condition, appetite, coughing, bothered by fevers, ability to work, hematuria and sleep). Each of the 15 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI score = sum of the 15 item scores; total range: 0 - 60; 0 (no symptoms) to 60 (very much); higher score indicated greater presence of symptoms/worse quality of life.

  8. EuroQol-5 Dimension-3 Level (EQ5D-3L) Scores at Baseline [ Time Frame: Baseline (Day 1 of Month 1) ]
    EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The mean of the summed score ranged from 1 to 3 with "1" corresponding to no problems and "3" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems. Total index EQ-5D-3L summary score is weighted with a range of -0.594 (worst) to 1.0 (best).

  9. Change From Baseline in EQ5D-3L Scores at Month 3 [ Time Frame: Baseline (Day 1 of Month 1), Month 3 ]
    EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

  10. Change From Baseline in EQ5D-3L Score at Month 6 [ Time Frame: Baseline (Day 1 of Month 1), Month 6 ]
    EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

  11. Change From Baseline in EQ5D-3L Score at Month 9 [ Time Frame: Baseline (Day 1 of Month 1), Month 9 ]
    EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

  12. Change From Baseline in EQ5D-3L Score at Last Follow-up [ Time Frame: Baseline (Day 1 of Month 1), last follow up visit (up to 33 months) ]
    EQ-5D-3L, a health profile questionnaire was used to assess quality of life along 5 dimensions. Participants rated 5 aspects of health (mobility, self-care, usual activities, pain/discomfort, and anxiety/depression) by choosing from 3 answering options (1=no problems; 2=some problems; 3=extreme problems). The summed score ranged from 1-15 with "1" corresponding to no problems and "15" corresponding to severe problems in the 5 dimensions, where higher score indicates more severe problems.

  13. Functional Assessment of Cancer Therapy Kidney Symptom Index-Disease-Related Symptoms (FKSI-DRS) Score at Baseline [ Time Frame: Baseline (Day 1 of Month 1) ]
    FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

  14. Change From Baseline in FKSI-DRS Score at Month 3 [ Time Frame: Baseline (Day 1 of Month 1), Month 3 ]
    FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

  15. Change From Baseline in FKSI-DRS Score at Month 6 [ Time Frame: Baseline (Day 1 of Month 1), Month 6 ]
    FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

  16. Change From Baseline in FKSI-DRS Score at Month 9 [ Time Frame: Baseline (Day 1 of Month 1), Month 9 ]
    FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.

  17. Change From Baseline in FKSI-DRS Score at Last Follow-up [ Time Frame: Baseline (Day 1 of Month 1), last follow up visit (up to 33 months) ]
    FKSI-DRS was used to assess quality of life in participants and consisted of 9 items (lack of energy, pain, losing weight, bone pain, fatigue, short of breath, coughing, bothered by fevers, and hematuria). Each of the 9 items was answered on a 5-point Likert scale ranging from 0 to 4 (0= not at all, 1= a little bit, 2= somewhat, 3= quite a bit, 4= very much). Total FKSI-DRS score = sum of the 9 item scores; total range: 0 - 36; 0 (no symptom) to 36 (very much); higher score indicated greater presence of symptom.


Secondary Outcome Measures :
  1. Overall Survival [ Time Frame: From the start of 3rd line treatment until death due to any cause (up to a maximum of 33 months) ]
    Overall survival was defined as the time from the start of 3rd line treatment until date of death due to any cause.

  2. Overall Survival at Year 1: Percentage of Participants Who Survived at Year 1 [ Time Frame: Baseline until death due to any cause (up to 1 year) ]
    Overall survival at Year 1 (Month 12) was defined as the time from the start of 3rd line treatment until death or 1 year due to any cause (measured at the end of 12 month follow-up/observation period). Percentage of participants who survived at the completion of 1 year (12 months) period were reported in this outcome measure.

  3. Time to Treatment Failure [ Time Frame: Baseline until disease progression or discontinuation, due to any cause (up to 33 months) ]
    Time to treatment failure was defined as the time from the start of treatment to the date of disease progression or date of permanent discontinuation. PD as per RECIST version 1.1 was defined as at least a 20% increase in the sum of longest dimensions of target lesions, reference to the smallest sum of the longest dimensions recorded since the treatment started, or the appearance of one or more new lesions or increase of at least 5 mm in addition to the relative increase of 20%.

  4. Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) [ Time Frame: Baseline up to 12 months ]
    An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. Treatment emergent AEs were events which occurred between start of disease treatment and up to Month 12 follow-up visit, that were absent before treatment or that worsened relative to pre-treatment state. AEs included both non-SAE and SAEs.

  5. Number of Participants With Grade 3 or Higher Severe Adverse Events (AEs) Based on NCI CTCAE Version 4.03 [ Time Frame: Baseline up to 12 months ]
    An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant and jeopardized the participants or required treatment to prevent other AE outcomes for any other reason: death; initial or prolonged inpatient hospitalization; life-threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. AEs were graded according to the National Cancer Institute- Common Terminology Criteria for Adverse Events (NCI CTCAE) version 4.03 and coded using the Medical Dictionary for Regulatory Activities (MedDRA) as Grade 1: Mild, Grade 2: Moderate, Grade 3: Severe, Grade 4: Life threatening, Grade 5: Death related to AE. AEs included both SAEs and non-SAEs.

  6. Number of Participants With Treatment-Emergent Adverse Events (AEs) During Third Line Targeted Treatment [ Time Frame: Baseline up to 12 months ]
    An AE was any untoward medical occurrence in a participant who received disease treatment without regard to possibility of causal relationship. Treatment emergent AEs during third line targeted treatment were events which occurred between first dose of third line targeted treatment and up to Month 12 follow-up visit, that were absent before treatment or that worsened relative to pre-treatment state.

  7. Number of Participants With Dose Modifications of Third-Line Treatment Due to Adverse Events [ Time Frame: Baseline up to Month 3, 6, 9 and 12 ]
    Number of participants that required dose modifications of third line treatment due to AEs were reported in this outcome measure. Dose modification was categorized as escalation (increase in dose), delay or interruptions (change in dose time or skipping any dose), reduction (decrease in dose).

  8. Correlation Coefficient Between Efficacy and Dose Modifications Due to AEs [ Time Frame: Baseline up to Month 12 follow-up visit ]
  9. Correlation Coefficient Between Efficacy and High Blood Pressure (>150 / 90 Millimeter of Mercury ) [ Time Frame: Baseline up to Month 12 follow-up visit ]


Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Sampling Method:   Probability Sample
Study Population
Metastatic renal cell carcinoma patients under 3rd line targeted therapy following 1st line interferon alpha and 2nd line TKI. All patients will be ≥ 18 years old and have signed the informed consent document.
Criteria

Inclusion criteria:

Patients must meet all of the following inclusion criteria to be eligible for inclusion in the study:

  • Histologically confirmed metastatic renal cell cancer patients who have already been using targeted therapies for up to 3 months as 3rd line treatment
  • Patients older than 18 years
  • Evidence of a personally signed and dated informed consent document indicating that the patient (or a legal representative) has been informed of all pertinent aspects of the study.

Exclusion criteria:

Patients meeting any of the following criteria will not be included in the study:

  • Patients with contraindications for the use of the study medications
  • Patients with (suspected) pregnancy or in lactation period
  • Patients who are investigational site staff members directly involved in the conduct of the trial and their family members, site staff members otherwise supervised by the Investigator, or patients who are Pfizer employees directly involved in the conduct of the trial.
  • Participation in other studies involving investigational drug(s) (Phases 1-4) within 4 weeks before included in the current study.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02315755


Locations
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Turkey
Gazi University
Ankara, Besevler, Turkey, 06500
Abdurrahman Yurtaslan Onkoloji Hastanesi
Ankara, Demetevler, Turkey, 06200
Marmara Üniversitesi Pendik Eğtim Araştırma Hastanesi
Pendik, İ̇stanbul, Turkey, 34899
Hacettepe University School of Medicine, Department of Medical Oncology
Ankara, Turkey, 06100
Ankara Numune Egitim Arastirma Hastanesi
Ankara, Turkey
Ege Universitesi Tip Fakultesi
Bornova/Izmir, Turkey, 35100
Ali Osman Sonmez Onkoloji Hastanesi
Bursa, Turkey
Dicle Universitesi Tip Fakultesi
Diyarbakir, Turkey, 21080
Trakya Universitesi Tip Fakultesi Ic Hastaliklari Anabilim Dali Tibbi Onkoloji Bilim Dal
Edirne, Turkey
Bezmialem Vakif Universitesi Tip Fakultesi Hastanesi
Istanbul, Turkey, 34093
Istanbul Universitesi Istanbul Tip Fakultesi Onkoloji Enstitusu
Istanbul, Turkey, 34390
Dokuz Eylul Universitesi Tip Fakultesi
Izmir, Turkey, 35340
Izmir Katip Celebi Universitesi Ataturk Egitim Arastirma Hastanesi Medikal Onkoloji Departmani
Izmir, Turkey, 35360
Dr Lufti Kirdar Kartal Egitim ve Arastirma Hastanesi
Kartal, Turkey
Konya Necmettin Erbakan Universitesi Meram Tip Fakultesi Tibbi Onkoloji Anabilim Dali
Konya, Turkey
Inonu Universitesi Tip Fakultesi Medikal Onkoloji Bilim Dali
Malatya, Turkey
Gaziantep Universitesi Tip Fakultesi
Sehitkamil/Gaziantep, Turkey, 27310
Erciyes Universitesi Tip Fakultesi
Talas / Kayseri, Turkey, 38039
Karadeniz Teknik Universitesi Tip Fakultesi Tibbi Onkoloji Bilim Dali
Trabzon, Turkey
Sponsors and Collaborators
Pfizer
Investigators
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Study Director: Pfizer CT.gov Call Center Pfizer
  Study Documents (Full-Text)

Documents provided by Pfizer:

Additional Information:
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Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT02315755     History of Changes
Other Study ID Numbers: A4061086
First Posted: December 12, 2014    Key Record Dates
Results First Posted: July 26, 2019
Last Update Posted: July 26, 2019
Last Verified: May 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No
Plan Description: Pfizer will provide access to individual de-identified participant data and related study documents (e.g. protocol, Statistical Analysis Plan (SAP), Clinical Study Report (CSR)) upon request from qualified researchers, and subject to certain criteria, conditions, and exceptions. Further details on Pfizer's data sharing criteria and process for requesting access can be found at: https://www.pfizer.com/science/clinical_trials/trial_data_and_results/data_requests.

Keywords provided by Pfizer:
Metastatic renal cell carcinoma, targeted molecular therapy

Additional relevant MeSH terms:
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Carcinoma
Carcinoma, Renal Cell
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Neoplasms
Adenocarcinoma
Kidney Neoplasms
Urologic Neoplasms
Urogenital Neoplasms
Neoplasms by Site
Kidney Diseases
Urologic Diseases