Neoplasms

Digestive System Diseases

All Conditions

Skin and Connective Tissue Diseases

Rare Diseases

Gastrointestinal Stromal Tumors

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Antineoplastic Agents

All Drugs and Chemicals

Sunitinib

Angiogenesis Inhibitors

Growth Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

sunitinib starting dose will be 15mg/m\^2 daily on a 4 weeks on/2 weeks off schedule (Schedule 4/2).

sunitinib malate dose escalation

sunitinib malate

Pfizer CT.gov Call Center

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.

A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor

A PHASE I/II STUDY OF SUNITINIB IN YOUNG PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR

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.

Estimated steady-state maximum plasma concentration (Cmax,ss) of Sunitinib and its metabolite SU012662. Summarized data for all time points was reported.

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.

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.

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.

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.

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.

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.

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).

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.

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).

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).

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.

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).

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.

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.

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).

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).

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).

Pfizer

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.

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.

Age, Continuous

Sex: Female, Male

White

Asian

Race/Ethnicity, Customized

The full analysis set (FAS) included all enrolled participants regardless of what treatment, if any, was received.

Pfizer ClinicalTrials.gov Call Center

SU012662

The PK population included all treated participants with at least one PK observation.

Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite

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 Oral Clearance (CL/F) of Sunitinib and Its Metabolite

Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite

Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite

Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite

SAEs

The as-treated population included all enrolled participants who received at least 1 dose of study drug.

Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)

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

Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)

Number of Participants With Clinically Significant Laboratory Abnormalities

Complete response

Partial response

The full analysis set included all enrolled participants regardless of what treatment, if any, was received.

Number of Participants With Objective Response

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.

Duration of Response

Progression-Free Survival

Overall Survival

Nausea

Vomiting

Diarrhoea

Fatigue

Palmar-Plantar Erythrodysaesthesia Syndrome

Neutropenia

Thrombocytopenia

Lymphopenia

Hypertension

Anaemia

Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 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) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) \< the median Ctrough value

Sunitinib: Lower Exposure

Participants who received Sunitinib capsules orally at a dose based on BSA (minimum dose of 15 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) and had total drug (sunitinib + SU012662) trough plasma concentration (Ctrough) \>= the median Ctrough value

Sunitinib: Higher Exposure

The PK subgroup analysis set included all treated participants with at least 1 PK observation.

Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups

Absolute Neutrophil Count: Cycle 1 Day 28

Absolute Neutrophil Count: Cycle 2 Day 28

Absolute Neutrophil Count: Cycle 3 Day 28

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

Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration

Systolic Blood Pressure: Cycle 1 Day 28

Systolic Blood Pressure: Cycle 2 Day 28

Systolic Blood Pressure: Cycle 3 Day 28

Diastolic Blood Pressure: Cycle 1 Day 28

Diastolic Blood Pressure: Cycle 2 Day 28

Diastolic Blood Pressure: Cycle 3 Day 28

Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration

Stable Disease

Partial Response

Complete Response

Progressive Disease

The PK population included all treated participants with at least 1 PK observation.

Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups

Progression Free Survival for PK Subgroups

Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration

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.

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

Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed

Spots Global Cancer Trial Database for A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor

Trial Identification

Conditions

Interventions

Study Description

Keywords

Eligibility

Locations

Contact Details

Useful links and downloads for this trial