Complete Remission in Renal Cell Carcinoma Clinical Trial
— APERCUOfficial title:
Prospective Study of Complete Remissions Observed With Sunitinib in Patients With Metastatic Renal Cell Carcinoma mRCC)
| Verified date | January 2023 |
| Source | Pfizer |
| Contact | n/a |
| Is FDA regulated | No |
| Health authority | |
| Study type | Observational |
This prospective study will investigate the characteristics of mRCC patients at time of CR in comparison with mRCC patients non on CR treated with Sunitinib, in order to provide some answers/ refection leads to the following questions : Can we identify blood specificity at time of CR vs non on CR? Shall we distinguish CR with sunitinib alone from combined CR (sunitinib with local treatment), while in clinical report these 2 cohorts present similar time to recurrence (ALBIGES, ASCO 2010)? Can we identify potential predictive serum biomarkers of recurrence? (With the aim of isolating blood biomarker that can help on treatment discontinuation decision?)
| Status | Completed |
| Enrollment | 77 |
| Est. completion date | January 19, 2022 |
| Est. primary completion date | January 19, 2022 |
| Accepts healthy volunteers | No |
| Gender | All |
| Age group | 18 Years to 99 Years |
| Eligibility | Inclusion Criteria: - Patients with metastatic renal cell carcinoma, histopathologically confirmed - Treated with sunitinib according to Smpc - For cases: Achieving a CR (local assessment according to RECIST V1.0 criteria) with Sunitinib in prior 6 months alone OR in combination with local treatment (surgery, radiation therapy, ablative techniques: cryotherapy, RFA) - For controls: Life expectancy > 3 months No prior Sunitinib treatment - Patient >18 years Exclusion Criteria: - Sunitinib administered in a non-approved label - For cases: CR occurring without sunitinib treatment - For controls: Prior systemic treatment |
| Country | Name | City | State |
|---|---|---|---|
| France | CHRU HOTEL DIEU - Service Urologie | Angers Cedex | |
| France | C.H.U Morvan | Brest | |
| France | Clinique Victor Hugo | Le Mans | |
| France | CHU de la Timone | Marseille | Cedex 5 |
| France | Hopital Timone Adultes | Marseille Cedex | |
| France | Institut Paoli-Calmettes | Marseille Cedex 09 | |
| France | Institut Paoli-Calmettes / Hôpital de jour | Marseille Cedex 9 | |
| France | CRLC Val d'Aurelle | Montpellier cedex 05 | |
| France | Hopital Europeen Georges Pompidou | Paris Cedex 15 | |
| France | Centre Hospitalier Lyon Sud | Pierre Bénite Cedex | |
| France | CHU Strasbourg | Strasbourg | Cedex |
| France | Clinique Chirurgicale de l'Orangerie, Chiliotherapie | Strasbourg | |
| France | Centre Alexis Vautrin | Vandoeuvre les Nancy | |
| France | Institut Gustave Roussy | Villejuif Cedex |
| Lead Sponsor | Collaborator |
|---|---|
| Pfizer |
France,
| Type | Measure | Description | Time frame | Safety issue |
|---|---|---|---|---|
| Other | Number of Participants Categorized According to Types of Blood Biomarkers | During follow up period maximum of 39.8 months for Cases and 37 months for Controls | ||
| Primary | Time to Diagnose Metastatic Renal Cell Carcinoma | Time to diagnose metastatic renal cell carcinoma was defined as the duration between date of diagnosis of mRCC to date of inclusion visit. | Baseline (at inclusion Visit) | |
| Primary | Number of Participants Categorized According to Presence of Nephrectomy | In this outcome measure, participants were categorized according to presence of nephrectomy as yes or no. | Baseline (at inclusion Visit) | |
| Primary | Number of Participants Categorized According to Type of Nephrectomy | In this outcome measure, participants were categorized according to type of nephrectomy. Various types of nephrectomies included: extended or partial, nephrectomy with or without adrenalectomy, nephrectomy with or without curettage and open or laparoscopic nephrectomy. | Baseline (at inclusion Visit) | |
| Primary | Time to Nephrectomy From Diagnosis of Metastatic Renal Cell Carcinoma (mRCC) | In this outcome measure, time from diagnosis of mRCC to nephrectomy was reported. | Baseline (at inclusion Visit) | |
| Primary | Number of Participants Categorized According to Pathological Classification | In this outcome measure, participants were categorized according to pathological classification. Pathological classification included: clear cell carcinoma (yes or no), multilocular cystic renal clear cell carcinoma (yes or no), papillary cell carcinoma (yes or no), chromophobe cell carcinoma(yes or no), Bellini's collecting duct carcinoma(yes or no), medullary cell carcinoma (yes or no), sarcomatoid contingent (yes or no), and other (yes or no). | Baseline (at inclusion Visit) | |
| Primary | Number of Participants Categorized According to Tumor, Node, Metastasis (TNM) Classification | In this outcome measure, participants were categorized according to TNM classification. TNM classification included: T class (1, 2, 3, 4), N (0,1,2, x) and M class (0, 1). TNM system is based on size of primary tumor (T), amount of spread to lymph nodes (N) and presence of metastases (M). T1: tumor (less than or equal to) <=20 millimeters (mm), T2: tumor >20 mm to <=50 mm, T3: >50 mm, T4: tumor invading other structures. N0: no lymph node metastases, N1: metastases to ipsilateral level I, II axillary lymph nodes, NX: Regional lymph nodes cannot be assessed. M0: no clinical/radiographic evidence of distant metastases, M1: distant detectable metastases as determined by clinical and radiographic means and/or histologically proven >0.2 mm. | Baseline (at inclusion Visit) | |
| Primary | Tumour Size | Tumour size of participants was reported in this outcome measure. | Baseline (at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Fuhrman Nuclear Grade | In this outcome measure, participants were categorized according to Fuhrman nuclear grade. The grades were classified as: grade 1, 2, 3, and 4. The four-tiered Fuhrman grading evaluates nuclear size, nuclear shape and presence of nucleolar prominence. Grade 1: small (=10 micrometer [mcm]) nuclear diameter, round/uniform nuclear shape and absent/inconspicuous nucleoli; Grade 2: large (=15 mcm) nuclear diameter, irregular outline nuclear shape and visible at *400 magnification nucleoli; Grade 3: larger (=20 mcm) nuclear diameter, obvious irregular outline nuclear shape and visible and prominent at *100 magnification nucleoli; Grade 4: grade 3 plus bizarre multilobed nuclei +/- spindle cells. | Baseline (at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Presence of Necrosis, Pulmonary Embolism and Sarcomatoid Component | In this outcome measure, participants were categorized according to presence of necrosis, pulmonary embolism and sarcomatoid component. | Baseline (at Inclusion Visit) | |
| Primary | Time to Initiation of Sunitinib From Diagnosis of Metastatic Renal Cell Carcinoma (mRCC) | Diagnosis of mRCC to Sunitinib Initiation (at Inclusion Visit) | ||
| Primary | Number of Participants Categorized According to Location of Metastases | In this outcome measure, participants were categorized according to location of metastases at different body parts (lung, bones, liver, adrenal gland, pancreas, brain and lymph nodes). Participant can have more than 1 location of metastases. | At initiation of sunitinib (at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Type of Lymph Nodes as Metastatic Site | In this outcome measure, participants were categorized according to type of lymph nodes as metastatic site. | At initiation of sunitinib (at Initiation Visit) | |
| Primary | Number of Participants Categorized According to Recurrence at Nephrectomy Site | In this outcome measure, participants were categorized according to recurrence at nephrectomy site were reported. | At initiation of sunitinib (at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Recurrence at Other Site | In this outcome measure, participants were categorized according to recurrence at any other site than nephrectomy site were reported. | At initiation of sunitinib (at Inclusion Visit) | |
| Primary | Number of Metastatic Sites | In this outcome measure, median of metastatic sites were reported. | At initiation of sunitinib (at Initiation Visit) | |
| Primary | Number of Participants Categorized According to Memorial Sloan-Kettering Cancer Center (MSKCC) Prognostic Classification | In this outcome measure, participants were categorized according MSKCC prognostic classification. MSKCC criteria had 5 risk factors: Karnofsky performance status (KPS) <80% (ability to perform ordinary tasks, 0 [dead] -100 [normal]); time from diagnosis to start of systemic therapy <12 months; hemoglobin | At initiation of sunitinib (at Inclusion Visit) |
| |
| Primary | Time to Achieve Complete Remission (CR) After Sunitinib Initiation: mRCC Participants With CR | In this outcome measure, time taken by participants to achieve the complete remission after sunitinib initiation were reported. As per Response Evaluation Criteria in Solid Tumors (RECIST) version (v) 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to size of <10 millimeter (mm). | From initiation of sunitinib till CR (data collected at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Method of Achieving CR: mRCC Participants With CR | In this outcome measure, participants were categorized according to the method of achieving the CR. Different methods included: treatment combined with local treatment and medical treatment alone. As per RECIST version 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | From initiation of sunitinib till CR (data collected at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Type of Medical Treatment Alone: mRCC Participants With CR | In this outcome measure, participants were categorized according to the type of medical treatment alone as method of achieving the CR. Medical treatment alone included: surgery, radiotherapy, radiofrequency, cryoablation and metastasectomy. Only those categories in which at least 1 participant had data were reported. Participant could have received more than 1 type of medical treatment. As per RECIST version 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | From initiation of sunitinib till CR (data collected at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Treatment Combined With Local Treatment: mRCC Participants With CR | In this outcome measure, participants were categorized according to the type of treatment Combined With local treatment alone as method of achieving the CR. Type of treatment combined with local treatment included: surgery, surgery + radiotherapy + radiofrequency + metastasectomy, metastasectomy, metastasectomy + other, radiofrequency + metastasectomy + other and radiotherapy. As per RECIST version 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | From initiation of sunitinib till CR (data collected at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Radiological Assessment of the CR: mRCC Participants With CR | In this outcome measure, participants were categorized according to radiological assessment of the CR. It included: disappearance of all known target lesions, disappearance of all non-target lesions, no new lesions and all target and non-target lymph nodes. Only those categories with at least 1 participant as result are reported. As per RECIST version 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | From initiation of sunitinib till CR (data collected at Inclusion Visit) | |
| Primary | Number of Participants Categorized According to Therapeutic Strategy After CR: mRCC Participants With CR | In this outcome measure, participants were categorized according to therapeutic strategy after CR. As per RECIST version 1.1 criteria: CR = disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumour marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). It included discontinuation and continuation of sunitinib treatment. | After achieving CR with sunitinib treatment (data collected at Inclusion Visit) | |
| Primary | Number of Participants With Disease Evolution (DE) at Month 12 Follow-up Visit: mRCC Participants With CR | DE included:complete response, progression, stabilization and not assessed. Disease progression (PD):per RECIST v1.1: at least 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study.In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm.Appearance of 1 or more new lesions was also considered progression. CR:disappearance of all target lesions.Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm.Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis) and stable disease (SD): absence of sufficient reduction for a partial response (PR): at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters or absence of a sufficient increase for PD, taking as reference the sum of lowest diameters during study. | Month 12 follow-up visit | |
| Primary | Number of Participants With Ongoing Sunitinib Treatment at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants with ongoing sunitinib treatment were reported. | Month 12 follow-up study visit | |
| Primary | Number of Participants With Ongoing Sunitinib Treatment According to Dose and Regimen at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants with ongoing sunitinib treatment according to dose (25, 37.5 and 50 mg) and regimen (4/2 [4 weeks dosing then 2 weeks off] and 2/1 [4 weeks dosing then 2 weeks off]) were reported. | Month 12 follow-up study visit | |
| Primary | Number of Participants Who Discontinued Sunitinib Temporarily at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants who temporarily discontinued sunitinib were reported. | Month 12 follow-up study visit | |
| Primary | Number of Participants Categorized According to Number of Temporary Discontinuations of Sunitinib Treatment at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants were categorized according to number (1 and 2) of temporary discontinuations of sunitinib. | Month 12 follow-up study visit | |
| Primary | Number of Instances When Different Types of Reason Led to Temporary Discontinuation of Sunitinib Treatment at Month 12 Follow up Visit: mRCC Participants With CR | In this outcome measure, number of instances when different types of reasons led to temporary discontinuations like intolerance, local treatment and other reasons were reported. Participant could have temporarily discontinued sunitinib treatment more than once. | Month 12 follow-up study visit | |
| Primary | Number of Instances When Participants Resumed Sunitinib Treatment After Temporary Discontinuation at Month 12: mRCC Participants With CR | In this outcome measure, number of instances when participants resumed sunitinib treatment were reported. Participant could have temporarily discontinued sunitinib treatment more than once and likewise resumed treatment more than once. | Month 12 follow-up study visit | |
| Primary | Duration of Temporary Discontinuation of Sunitinib Treatment at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, duration of temporary discontinuation of sunitinib treatment were reported. | Month 12 follow-up study visit | |
| Primary | Number of Participants Who Discontinued Sunitinib Permanently at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, number of participants who permanently discontinued sunitinib were reported. | Month 12 follow-up study visit | |
| Primary | Number of Participants Categorized According to Reasons for Permanent Discontinuations of Sunitinib Treatment at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants were categorized according to reasons for permanent discontinuation of sunitinib. | Month 12 follow-up visit | |
| Primary | Duration of Treatment With Sunitinib Since Complete Remission at Month 12 Follow-up Visit: mRCC Participants With CR | In this outcome measure, duration of treatment with sunitinib since complete remission was reported. | Month 12 follow-up study visit | |
| Primary | Number of Participants With Disease Evolution at Month 24 Follow-up Visit: mRCC Participants With CR | DE included: CR, PD, SD and not assessed. PD: per RECIST v1.1: at least a 20% increase in sum of diameters of target lesions, taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm. Appearance of one or more new lesions was also considered progression. CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis).SD: absence of sufficient reduction for PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters or absence of a sufficient increase for PD, taking as reference the sum of lowest diameters during study. | Month 24 follow-up study visit | |
| Primary | Number of Participants With Ongoing Sunitinib Treatment at Month 24 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants with ongoing sunitinib treatment were reported. | Month 24 follow-up study visit | |
| Primary | Number of Participants Who Discontinued Sunitinib Temporarily at Month 24 Follow-up Visit: mRCC Participants With CR | In this outcome measure, number of participants who temporarily discontinued sunitinib were reported. | Month 24 follow-up study visit | |
| Primary | Number of Participants Who Resumed Treatment at Month 24 Follow-up Visit: mRCC Participants With CR | In this outcome measure, participants who resumed sunitinib were reported. | Month 24 follow-up study visit | |
| Primary | Number of Days of Temporary Discontinuation of Sunitinib Treatment at Month 24 Follow-up Visit: mRCC Participants With CR | Month 24 follow-up study visit | ||
| Primary | Number of Participants Who Discontinued Sunitinib Permanently at Month 24 Follow-up Visit: mRCC Participants With CR | Month 24 follow-up study visit | ||
| Primary | Number of Participants Categorized According to Reasons for Permanent Discontinuations of Sunitinib Treatment at Month 24 Follow-up Visit: mRCC Participants With CR | Month 24 follow-up study visit | ||
| Primary | Duration of Treatment With Sunitinib Since Complete Remission at Month 24 Follow-up Visit: mRCC Participants With CR | CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | Month 24 follow-up study visit | |
| Primary | Time to Progression With Sunitinib Treatment From Complete Remission: mRCC Participants With CR | CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). PD: =>20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of longest dimensions since treatment start or appearance of =>1 new lesions. | From achieving CR with Sunitinib treatment (before inclusion in the study, participants recruited for 3 years) to Visit at progression (during study); [post inclusion follow-up in the study was maximum of 39.8 months for Cases] | |
| Primary | Duration of Additional Treatment With Sunitinib Since Complete Remission: mRCC Participants With CR | CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | From complete remission (before inclusion in the study, participants recruited for 3 years) till discontinuation of additional treatment during this study; [post inclusion follow-up in the study was maximum of 39.8 months for Cases] | |
| Primary | Number of Participants Categorized According to Types of Progression: mRCC Participants With CR | As per RECIST version 1.1, PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. | Study visit at progression; post inclusion follow-up in the study was maximum of 39.8 months for Cases | |
| Primary | Number of Participants Categorized According to Site of Progression: mRCC Participants With CR | As per RECIST version 1.1, PD was defined as at least a 20% increase in sum of diameters of target lesions, taking as reference the smallest sum on study. In addition to relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. The appearance of one or more new lesions was also considered progression. | Study visit at progression; post inclusion follow-up in the study was maximum of 39.8 months for Cases | |
| Primary | Number of Participants Categorized According to Location of Metastases: mRCC Participants With CR | In this outcome measure, participants were categorized according to location of metastases at different body parts (lung, bones, liver, adrenal glands, pancreas, brain, lymph nodes, recurrence at nephrectomy site and other). Participant could have more than 1 location of metastases. | Study visit at progression; post inclusion follow-up in the study was maximum of 39.8 months for Cases | |
| Primary | Number of Participants Categorized According to Type of Lymph Nodes as Metastatic Site: mRCC Participants With CR | In this outcome measure, participants were categorized according to type of lymph nodes as metastatic site were reported. | Study visit at progression; post inclusion follow-up in the study was maximum of 39.8 months for Cases | |
| Primary | Number of Participants Categorized According to Number of Metastatic Sites: mRCC Participants With CR | In this outcome measure, participants were categorized according to number of metastatic sites (1, 2 and 3). | Study visit at progression; post inclusion follow-up in the study was maximum of 39.8 months for Cases | |
| Primary | Number of Participants Who Received Systemic Treatment After Progression: mRCC Participants With CR | In this outcome measure, participants who received systemic treatment after progression were reported. | After progression, during follow up period maximum of 39.8 months for Cases | |
| Primary | Number of Participants Categorized According to Type of Systemic Treatment Received After Progression: mRCC Participants With CR | In this outcome measure, participants who received systemic treatment after progression were categorized according to type of treatment. Different types of treatment were tyrosine kinase inhibitor- sunitinib restart, radiotherapy and other systemic treatment. Participant could have more than 1 type of treatment. | After progression, during follow up period maximum of 39.8 months for Cases | |
| Primary | Number of Participants With Best Objective Response After Progression: mRCC Participants With CR | Participants with best objective response after progression were evaluated here. It included complete, partial, stabilized and not applicable. PD per RECIST v1.1: at least a 20% increase in sum of diameters of target lesions,taking as reference smallest sum on study. In addition to relative increase of 20%, sum must also demonstrate an absolute increase of at least 5mm. Appearance of one or more new lesions was also considered progression. CR:disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis) & SD: absence of sufficient reduction for a PR: at least 30% decrease in sum of diameters of target lesions, taking as reference baseline sum diameters or absence of a sufficient increase for PD, taking as reference the sum of lowest diameters during study. | At the end of study visit follow-up (during follow up period maximum of 39.8 months for Cases) | |
| Primary | Duration of Treatment With First Line Sunitinib Till Progression: mRCC Participants With CR | CR: disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10 mm. Disappearance of all non-target lesions and normalization of tumor marker level. All lymph nodes must be non-pathological in size (<10 mm short axis). | Sunitinib initiation (before inclusion, participants recruited for 3 years) till progression (follow up period maximum of 39.8 months for Cases) | |
| Primary | Number of Participants Who Were Early Terminated: mRCC Participants With CR | Participants who terminated study early were reported in this outcome measure. | From inclusion in the study till termination (during follow up period maximum of 39.8 months for Cases) | |
| Primary | Number of Participants Who Achieved Response: mRCC Participants With CR | At initiation of sunitinib (during follow up period maximum of 39.8 months for Cases) | ||
| Primary | Number of Participants Categorized According to Number of Subsequent Treatment Lines From Progression/Post Complete Remission: mRCC Participants With CR | At initiation of sunitinib (during follow up period maximum of 39.8 months for Cases) | ||
| Primary | Number of Participants Who Died: mRCC Participants With CR | In this outcome measure, participants who died during the study were reported. | At initiation of sunitinib (during follow up period maximum of 39.8 months for Cases) | |
| Primary | Progression Free Survival: mRCC Participants With CR | PFS was based on Kaplan-Meier estimates. PFS was defined as time in months from start of treatment-to-treatment discontinuation due to disease progression as assessed by the investigator. PD: =>20% increase in sum of longest dimensions of lesions taking as a reference smallest sum of longest dimensions since treatment start or appearance of =>1 new lesions. Disease progression was determined from oncologic assessment data (where data meet the criteria for PD), or from death case report forms (CRFs). This outcome measure was analyzed by using Kaplan-Meier method. | At the end of the study (inclusion period was of 3 years and follow up period maximum of 39.8 months for Cases) | |
| Primary | Number of Participants With Adverse Events and Serious Adverse Events | An adverse event (AE) was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. A serious AE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. | During follow up period maximum of 39.8 months for Cases and 37 months for Controls | |
| Primary | Number of Participants With Adverse Events and Serious Adverse Events Possibly Related to Drug Exposure | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, possibly considered related to the study treatment. A serious AE was any untoward medical occurrence that, at any dose: resulted in death; required inpatient hospitalization or prolongation of existing hospitalization; was life-threatening; resulted in persistent or significant disability/ incapacity; congenital anomaly/birth defect and other important medical events. | During follow up period maximum of 39.8 months for Cases and 37 months for Controls | |
| Primary | Number of AEs According to Action Taken for the Study Treatment in Response to Those AEs | An AE was any untoward medical occurrence in a participant, temporally associated with the use of study treatment, whether or not considered related to the study treatment. | During follow up period maximum of 39.8 months for Cases and 37 months for Controls |