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| ID | Type | Description | Link |
|---|---|---|---|
| 2011-002008-33 | EudraCT Number |
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Children and young adults with gastrointestinal stromal tumors (GIST) will be treated with sunitinib. The safety (including pharmacokinetics) and tolerability of sunitinib will be studied in these patients. In addition, tumor responses and overall survival will be assessed.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Children with GIST | Experimental | children ages 6yrs-<18yrs |
|
| Young adults with GIST | Experimental | young adults ages 18yrs-<21 yrs |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| sunitinib malate dose escalation | Drug | sunitinib starting dose will be 15mg/m^2 daily on a 4 weeks on/2 weeks off schedule (Schedule 4/2). |
|
| Measure | Description | Time Frame |
|---|---|---|
| Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite | Estimated steady-state maximum plasma concentration (Cmax,ss) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported. | pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1 |
| Estimated Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose AUC(0-24) of Sunitinib and Its Metabolite | Estimated area under the plasma concentration versus time curve from time zero to 24 hours post dose (AUC24) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported. | pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1 |
| Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite | SU012662 is the metabolite of Sunitinib. Oral clearance (CL/F) is a quantitative measure of the rate at which a drug substance is removed from the blood (CL) normalized by the oral bioavailability of the drug (F). Summarized data for all time points was reported. | pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1 |
| Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite | SU012662 is the metabolite of Sunitinib. | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
| Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite | SU012662 is the metabolite of Sunitinib. | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
| Measure | Description | Time Frame |
|---|---|---|
| Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant 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 were events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious adverse events (AEs) and SAEs. |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Pfizer CT.gov Call Center | Pfizer | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles | Los Angeles | California | 90027 | United States | ||
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33852135 | Derived | Wang E, DuBois SG, Wetmore C, Verschuur AC, Khosravan R. Population Pharmacokinetics of Sunitinib and its Active Metabolite SU012662 in Pediatric Patients with Gastrointestinal Stromal Tumors or Other Solid Tumors. Eur J Drug Metab Pharmacokinet. 2021 May;46(3):343-352. doi: 10.1007/s13318-021-00671-7. Epub 2021 Apr 14. | |
| 31006038 |
| Label | URL |
|---|---|
| To obtain contact information for a study center near you, click here. | View source |
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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.
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| ID | Title | Description |
|---|---|---|
| FG000 | Sunitinib | Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met. |
| Title | Milestones | Reasons Not Completed | ||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
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The full analysis set (FAS) included all enrolled participants regardless of what treatment, if any, was received.
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| ID | Title | Description |
|---|---|---|
| BG000 | Sunitinib | Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met. |
| Units | Counts |
|---|---|
| Participants |
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| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite | Estimated steady-state maximum plasma concentration (Cmax,ss) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported. | The PK population included all treated participants with at least one PK observation. | Posted | Mean | Standard Deviation | nanograms per milliliter (ng/mL) | pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1 |
|
Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)
Same event may appear as both an AE and SAE. However, what is presented are distinct events. An event may be categorized as serious in one participant and as non-serious in another, or a participant may have experienced both a serious and non-serious event.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | Sunitinib | Participants received Sunitinib capsules orally at a dose based on body surface area (BSA) (minimum dose of 15 milligram/ meter square [mg/m^2] up to a maximum dose of 30 mg/m^2) once daily, from Day 1 to 28 in each treatment cycle of 42 days (up to a maximum of 18 cycles) until completion of study treatment, disease progression, unacceptable toxicity, required a treatment rest (greater than [>4] weeks), withdrawal of participant consent, or if other withdrawal criteria were met. |
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| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Anaemia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Pfizer ClinicalTrials.gov Call Center | Pfizer, Inc. | 1-800-718-1021 | ClinicalTrials.gov_Inquiries@pfizer.com |
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| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot | Yes | No | No | Study Protocol | Jul 31, 2017 | Feb 9, 2018 | Prot_000.pdf |
| SAP | No | Yes | No | Statistical Analysis Plan | Jul 15, 2011 | Feb 9, 2018 | SAP_001.pdf |
| ID | Term |
|---|---|
| D046152 | Gastrointestinal Stromal Tumors |
| ID | Term |
|---|---|
| D009372 | Neoplasms, Connective Tissue |
| D018204 | Neoplasms, Connective and Soft Tissue |
| D009370 | Neoplasms by Histologic Type |
| D009369 | Neoplasms |
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| ID | Term |
|---|---|
| D000077210 | Sunitinib |
| ID | Term |
|---|---|
| D011758 | Pyrroles |
| D001393 | Azoles |
| D006573 | Heterocyclic Compounds, 1-Ring |
| D006571 | Heterocyclic Compounds |
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| sunitinib malate | Drug | sunitinib 50mg daily on Schedule 4/2 |
|
| Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite |
AUC(0-8) was defined as area under the plasma concentration time-curve from time zero to 8 hours post dose. SU012662 is the metabolite of Sunitinib. |
| Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
| Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
| Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0 | An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Treatment-emergent events are events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported. | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
| Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant 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 included both non-serious adverse events (AEs) and SAEs. | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
| Number of Participants With Clinically Significant Laboratory Abnormalities | Criteria for clinically significant laboratory abnormalities: Hemoglobin (Hb), hematocrit: less than (<) 0.8*lower limit of normal (LLN), platelet: <75 or greater than (>) 700*10^3/millimeter (mm)^3*upper limit of normal (ULN), leukocyte: <2.5 or >17.5*10^3/mm^3*ULN; total bilirubin 1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase: >3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN ;blood urea nitrogen, creatinine: >1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, calcium: <0.9*LLN or >1.1*ULN, albumin, total protein <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, creatine kinase >2.0*ULN; urine (red blood cell, white blood cell >6/high power field). | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
| Number of Participants With Objective Response | Objective response in participants was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30 percentage (%) decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
| Duration of Response | Duration of response was defined as time (in months) from the first documentation of objective tumor response (confirmed CR or PR) to the first documentation of disease progression or death due to any cause. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
| Progression-Free Survival | Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
| Overall Survival | Overall survival was defined as time (in months) from enrollment to the date of death due to any cause. Analysis was performed using Kaplan-Meier method. | Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
| Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE version 4.0, Grade1= asymptomatic or mild symptoms, Grade 2= Moderate;local or noninvasive intervention indicated; Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Participants with any of the Grade 1 to Grade 5 AEs were reported. The PK evaluable participants were divided into 2 PK subgroups on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure). | Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days) |
| Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration | Pearson correlation coefficient between percent change from baseline in laboratory parameters with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Laboratory parameters included absolute neutrophil count, platelet count, lymphocyte count and hemoglobin. | Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days) |
| Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration | Pearson correlation coefficient between percent change from baseline in vital sign results with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Vital signs included systolic blood pressure and diastolic blood pressure. | Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days) |
| Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups | SD:when there is no sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR: as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. CR: disappearance of all lesions (target and non-target). PD:at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants with SD, PR, CR and PD responses were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure). | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first(maximum duration: up to Cycle 18; each cycle was of 42 days) |
| Progression Free Survival for PK Subgroups | Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The PK evaluable participants were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure). | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
| Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration | Pearson correlation coefficient between Progression Free Survival (PFS) with total drug (Sunitinib + SU012662) concentration at Day 28 of Cycle 1 was calculated. PFS was defined as time (in months) from date of enrolment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days |
| Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Efficacy Parameter (e.g., Sum of Largest Diameters for Target Tumors) Was Observed | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
| Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
| Children's Hospital Boston |
| Boston |
| Massachusetts |
| 02115 |
| United States |
| Dana-Farber Cancer Institute | Boston | Massachusetts | 02215 | United States |
| Fakultni nemocnice Brno | Brno | 613 00 | Czechia |
| FN Brno | Brno | 625 00 | Czechia |
| Masarykuv onkologicky ustav | Brno | 656 33 | Czechia |
| CHU de La Timone, Hopital enfants | Marseille | 13385 | France |
| Hopital d'Enfants de la Timone | Marseille | 13385 | France |
| Hopital de la Timone | Marseille | 13385 | France |
| Verschuur AC, Bajciova V, Mascarenhas L, Khosravan R, Lin X, Ingrosso A, Janeway KA. Sunitinib in pediatric patients with advanced gastrointestinal stromal tumor: results from a phase I/II trial. Cancer Chemother Pharmacol. 2019 Jul;84(1):41-50. doi: 10.1007/s00280-019-03814-5. Epub 2019 Apr 20. |
| years |
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| Sex: Female, Male | Count of Participants | Participants |
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| Race/Ethnicity, Customized | Number | participants |
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| Primary | Estimated Area Under the Plasma Concentration Versus Time Curve From Time Zero to 24 Hours Post Dose AUC(0-24) of Sunitinib and Its Metabolite | Estimated area under the plasma concentration versus time curve from time zero to 24 hours post dose (AUC24) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported. | The PK population included all treated participants with at least one PK observation. | Posted | Mean | Standard Deviation | nanogram*hour per milliliter (ng*hr)/mL | pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1 |
|
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|
| Primary | Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite | SU012662 is the metabolite of Sunitinib. Oral clearance (CL/F) is a quantitative measure of the rate at which a drug substance is removed from the blood (CL) normalized by the oral bioavailability of the drug (F). Summarized data for all time points was reported. | The PK population included all treated participants with at least one PK observation. | Posted | Mean | Standard Deviation | Liters per hour (L/hr) | pre-dose on Day 1, Day 12-18 and Day 25-29 of Cycle 1,2, 3 and 2, 4, 6, 8 hours post-dose on Day 1 Cycle 1 |
|
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| Primary | Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite | SU012662 is the metabolite of Sunitinib. | The PK population included all treated participants with at least one PK observation. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms per milliliter (ng/mL) | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
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| Primary | Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite | SU012662 is the metabolite of Sunitinib. | The PK population included all treated participants with at least one PK observation. | Posted | Median | Full Range | hours | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
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| Primary | Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite | AUC(0-8) was defined as area under the plasma concentration time-curve from time zero to 8 hours post dose. SU012662 is the metabolite of Sunitinib. | The PK population included all treated participants with at least one PK observation. | Posted | Geometric Mean | Geometric Coefficient of Variation | nanograms*hour per milliliter (ng*hr)/mL | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
|
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE was an AE resulting in any of the following outcomes or deemed significant 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 were events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. AEs included both non-serious adverse events (AEs) and SAEs. | The as-treated population included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
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| Secondary | Number of Participants With Treatment-Emergent Adverse Events (AEs) Greater Than or Equal to (>=) Grade 3, Based on National Cancer Institute (NCI) Common Terminology Criteria (CTC) for AEs (CTCAE), Version 4.0 | An AE is any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE, Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Treatment-emergent events are events between first dose of study drug and up to end of study (up to Cycle 18) that were absent before treatment or that worsened relative to pretreatment state. Number of participants with AEs of any of the Grade 3 or above (Grade 4, 5) were reported. | The as-treated population included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
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| Secondary | Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs) | An AE was any untoward medical occurrence attributed to study drug in a participant who received study drug. An SAE was an AE resulting in any of the following outcomes or deemed significant 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 included both non-serious adverse events (AEs) and SAEs. | The as-treated population included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
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| Secondary | Number of Participants With Clinically Significant Laboratory Abnormalities | Criteria for clinically significant laboratory abnormalities: Hemoglobin (Hb), hematocrit: less than (<) 0.8*lower limit of normal (LLN), platelet: <75 or greater than (>) 700*10^3/millimeter (mm)^3*upper limit of normal (ULN), leukocyte: <2.5 or >17.5*10^3/mm^3*ULN; total bilirubin 1.5*ULN, aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyl transferase: >3.0*ULN, total protein, albumin: <0.8*LLN or >1.2*ULN ;blood urea nitrogen, creatinine: >1.3*ULN, uric acid >1.2*ULN; sodium <0.95*LLN or >1.05*ULN, potassium, calcium: <0.9*LLN or >1.1*ULN, albumin, total protein <0.8*LLN or >1.2*ULN; glucose <0.6*LLN or >1.5*ULN, creatine kinase >2.0*ULN; urine (red blood cell, white blood cell >6/high power field). | The as-treated population included all enrolled participants who received at least 1 dose of study drug. | Posted | Number | participants | Baseline up to end of study (up to Cycle 18, each cycle was of 42 days) |
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| Secondary | Number of Participants With Objective Response | Objective response in participants was defined as the number of participants with confirmed complete response (CR) or partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30 percentage (%) decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. | The full analysis set included all enrolled participants regardless of what treatment, if any, was received. | Posted | Number | participants | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
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| Secondary | Duration of Response | Duration of response was defined as time (in months) from the first documentation of objective tumor response (confirmed CR or PR) to the first documentation of disease progression or death due to any cause. Confirmed response were those that persisted on repeat imaging study for at least 4 weeks after initial documentation of response. CR was defined as disappearance of all lesions (target and non-target). PR was defined as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | Analysis was performed on a subset of FAS which included participants who had a confirmed CR or PR. Since, none of the participants had confirmed CR or PR, hence duration of response was not analyzed. | Posted | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
|
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| Secondary | Progression-Free Survival | Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | The full analysis set included all enrolled participants regardless of what treatment, if any, was received. | Posted | Median | 95% Confidence Interval | months | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
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| Secondary | Overall Survival | Overall survival was defined as time (in months) from enrollment to the date of death due to any cause. Analysis was performed using Kaplan-Meier method. | The full analysis set included all enrolled participants regardless of what treatment, if any, was received. | Posted | Median | 95% Confidence Interval | months | Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
|
|
|
| Secondary | Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups | An AE was any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. As per NCI CTCAE version 4.0, Grade1= asymptomatic or mild symptoms, Grade 2= Moderate;local or noninvasive intervention indicated; Grade 3 events =medically significant but not immediately life-threatening, unacceptable or intolerable events, significantly interrupting usual daily activity, require systemic drug therapy/other treatment, Grade 4 events =participant to be in imminent danger of death. Grade 5 events =death. Participants with any of the Grade 1 to Grade 5 AEs were reported. The PK evaluable participants were divided into 2 PK subgroups on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure). | The PK subgroup analysis set included all treated participants with at least 1 PK observation. | Posted | Number | participants | Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days) |
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|
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| Secondary | Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration | Pearson correlation coefficient between percent change from baseline in laboratory parameters with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Laboratory parameters included absolute neutrophil count, platelet count, lymphocyte count and hemoglobin. | The PK population included all treated participants with at least one PK observation. | Posted | Number | correlation coefficient | Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days) |
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| Secondary | Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration | Pearson correlation coefficient between percent change from baseline in vital sign results with total drug (Sunitinib + SU012662) concentration were calculated on Day 28 of Cycles 1, 2, and 3. Vital signs included systolic blood pressure and diastolic blood pressure. | The PK population included all treated participants with at least one PK observation. | Posted | Number | correlation coefficient | Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days) |
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| Secondary | Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups | SD:when there is no sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum diameters while on study. PR: as at least 30% decrease in the sum of the longest dimensions of target lesions taking as a reference the baseline sum longest dimensions, with non-target lesions not increased or absent. CR: disappearance of all lesions (target and non-target). PD:at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). Participants with SD, PR, CR and PD responses were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure). | The PK population included all treated participants with at least 1 PK observation. | Posted | Number | participants | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first(maximum duration: up to Cycle 18; each cycle was of 42 days) |
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| Secondary | Progression Free Survival for PK Subgroups | Progression free survival was defined as time (in months) from date of enrollment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). The PK evaluable participants were assessed according to 2 PK subgroups created on Day 28 of Cycle 1: those with total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) value less than (<) the median Ctrough value(lower exposure) and those with total drug (sunitinib + SU012662) Ctrough values greater than or equal to (>=) the median Ctrough value(higher exposure). | The PK population included all treated participants with at least one PK observation. | Posted | Median | 95% Confidence Interval | months | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days) |
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| Secondary | Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration | Pearson correlation coefficient between Progression Free Survival (PFS) with total drug (Sunitinib + SU012662) concentration at Day 28 of Cycle 1 was calculated. PFS was defined as time (in months) from date of enrolment to the first documentation of disease progression or to death (due to any cause), whichever occurred first. Progression was defined as at least a 20% increase in the sum of diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). | The PK population included all treated participants with at least one PK observation. | Posted | Number | correlation coefficient | Baseline until disease progression or discontinuation from the study, or death, whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days |
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| Secondary | Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Efficacy Parameter (e.g., Sum of Largest Diameters for Target Tumors) Was Observed | Due to low number of enrolled participants (n=6), there was insufficient data to perform any type of pharmacokinetic/pharmacodynamic modeling to obtain EC50 values, hence data is not reported. | Posted | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
|
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| Secondary | Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed | Due to low number of enrolled participants (n=6), there was insufficient data to perform any type of pharmacokinetic/pharmacodynamic modeling to obtain EC50 values, hence data is not reported. | Posted | Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose |
|
|
| 0 |
| 6 |
| 0 |
| 6 |
| 6 |
| 6 |
| Leukopenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Lymphopenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Neutropenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Thrombocytopenia | Blood and lymphatic system disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Palpitations | Cardiac disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hypothyroidism | Endocrine disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Vision blurred | Eye disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Abdominal pain | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Constipation | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Diarrhoea | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Dyspepsia | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Impaired gastric emptying | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Intra-abdominal haemorrhage | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Lip discolouration | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Nausea | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Sensitivity of teeth | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Vomiting | Gastrointestinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Asthenia | General disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Chest pain | General disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Fatigue | General disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hepatic haematoma | Hepatobiliary disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Ear infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Folliculitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Herpes simplex | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Nasopharyngitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Otitis media | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Sinusitis | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Tooth infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Upper respiratory tract infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Viral infection | Infections and infestations | MedDRA v20.0 | Non-systematic Assessment |
|
| Alanine aminotransferase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Amylase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Aspartate aminotransferase increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Blood alkaline phosphatase | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Blood phosphorus increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Blood uric acid increased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Eosinophil count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Lymphocyte count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Neutrophil count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Weight decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| White blood cell count decreased | Investigations | MedDRA v20.0 | Non-systematic Assessment |
|
| Decreased appetite | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hyperglycaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hyperkalaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hypermagnesaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hypocalcaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hypoglycaemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hypophosphataemia | Metabolism and nutrition disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Back pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Muscle spasms | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Musculoskeletal stiffness | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Myalgia | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Neck pain | Musculoskeletal and connective tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Migraine | Nervous system disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Insomnia | Psychiatric disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Epistaxis | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Nasal congestion | Respiratory, thoracic and mediastinal disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Acne | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Alopecia | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Erythema | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Hair colour changes | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Palmar-plantar erythrodysaesthesia syndrome | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Pruritus | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
| Rash | Skin and subcutaneous tissue disorders | MedDRA v20.0 | Non-systematic Assessment |
|
Pfizer has the right to review disclosures, requesting a delay of less than 60 days. Investigator will postpone single center publications until after disclosure of pooled data (all sites), less than 12 months from study completion/termination at all participating sites. Investigator may not disclose previously undisclosed confidential information other than study results.
| D005770 | Gastrointestinal Neoplasms |
| D004067 | Digestive System Neoplasms |
| D004066 | Digestive System Diseases |
| D005767 | Gastrointestinal Diseases |
| D007211 |
| Indoles |
| D006574 | Heterocyclic Compounds, 2-Ring |
| D000072471 | Heterocyclic Compounds, Fused-Ring |
| Diarrhoea |
|
| Fatigue |
|
| Palmar-Plantar Erythrodysaesthesia Syndrome |
|
| Neutropenia |
|
| Thrombocytopenia |
|
| Lymphopenia |
|
| Hypertension |
|
| Anaemia |
|
| Title | Measurements |
|---|---|
|
| Platelet Count: Cycle 1 Day 28 |
|
| Platelet Count: Cycle 2 Day 28 |
|
| Platelet Count: Cycle 3 Day 28 |
|
| Lymphocyte Count: Cycle 1 Day 28 |
|
| Lymphocyte Count: Cycle 2 Day 28 |
|
| Lymphocyte Count: Cycle 3 Day 28 |
|
| Hemoglobin: Cycle 1 Day 28 |
|
| Hemoglobin: Cycle 2 Day 28 |
|
| Hemoglobin: Cycle 3 Day 28 |
|
| Title | Measurements |
|---|---|
|
| Diastolic Blood Pressure: Cycle 1 Day 28 |
|
| Diastolic Blood Pressure: Cycle 2 Day 28 |
|
| Diastolic Blood Pressure: Cycle 3 Day 28 |
|
| Complete Response |
|
| Progressive Disease |
|