Clinical trial NCT01396148: A Study of Sunitinib In Young Patients With Advanced Gastrointestinal Stromal Tumor
Official title: A PHASE I/II STUDY OF SUNITINIB IN YOUNG PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Gastrointestinal Stromal Tumors
Keywords: Children and young adults with GIST
sunitinib malate
pharmacokinetics
tumor response
overall survival
tumor KIT mutation status
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2011-07-18
Enrollment: 6
Sex: ALL
Minimum age (years): 6
Maximum age (years): 20
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Primary purpose: TREATMENT

Brief summary: 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.


Eligibility criteria: Inclusion Criteria:

* Histological diagnosis of GIST.
* Patients must have demonstrated either disease progression or intolerance to imatinib mesylate, have non-mutant Stem Cell Factor Receptor gene (KIT) GIST, or cannot obtain imatinib in their country
* Measurable by Response Evaluation Criterion in Solid Tumors (RECIST) or evaluable disease.

Exclusion Criteria:

* Current treatment with another investigational agent.
* Prior sunitinib treatment.
* Prior therapy with known risk for cardiovascular complications.

Primary outcomes:
measure: Estimated Steady-State Maximum Plasma Concentration (Cmax,ss) of Sunitinib and Its Metabolite
timeFrame: 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
measure: 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
timeFrame: 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
measure: Estimated Oral Clearance (CL/F) of Sunitinib and Its Metabolite
timeFrame: 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
measure: Maximum Observed Plasma Concentration (Cmax) of Sunitinib and Its Metabolite
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
measure: Time to Reach Maximum Observed Plasma Concentration (Tmax) for Sunitinib and Its Metabolite
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
measure: Area Under the Plasma Concentration-Time Curve From Time Zero to 8 Hours Post Dose AUC(0-8) for Sunitinib and Its Metabolite
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
Secondary outcomes:
measure: Number of Participants With Treatment-Emergent Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)
measure: 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
timeFrame: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)
measure: Number of Participants With Treatment-Related Adverse Events (AEs) and Serious Adverse Events (SAEs)
timeFrame: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)
measure: Number of Participants With Clinically Significant Laboratory Abnormalities
timeFrame: Baseline up to end of study (up to Cycle 18, each cycle was of 42 days)
measure: Number of Participants With Objective Response
timeFrame: 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)
measure: Duration of Response
timeFrame: 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)
measure: Progression-Free Survival
timeFrame: 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)
measure: Overall Survival
timeFrame: Baseline until death or discontinuation from the study whichever occurred first (maximum duration: up to Cycle 18; each cycle was of 42 days)
measure: Number of Participants With Adverse Events Based on National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) for Pharmacokinetic (PK) Subgroups
timeFrame: Cycle 1 Day 28 up to Cycle 3 (each cycle 42 days)
measure: Pearson Correlation Coefficient Between Percent Change From Baseline in Laboratory Parameters With Total Drug (Sunitinib + SU012662) Concentration
timeFrame: Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)
measure: Pearson Correlation Coefficient Between Percent Change From Baseline in Vital Sign Results With Total Drug (Sunitinib + SU012662) Concentration
timeFrame: Baseline, Day 28 of Cycle 1, Cycle 2 and Cycle 3 (each cycle was of 42 days)
measure: Number of Participants With Stable Disease (SD), Partial Response (PR), Complete Response (CR) and Progressive Disease (PD) for PK Sub-groups
timeFrame: 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)
measure: Progression Free Survival for PK Subgroups
timeFrame: 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)
measure: Pearson Correlation Coefficient Between Progression Free Survival With Total Drug (Sunitinib + SU012662) Concentration
timeFrame: 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
measure: 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
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
measure: Estimated Sunitinib Plasma Concentration at Which 50% of the Maximum Effect (EC50) for Each Selected Safety Endpoint (e.g., Absolute Neutrophil Count) Was Observed
timeFrame: Cycle 1 Day 1: pre-dose, 2, 4, 6, and 8 hours post-dose
Other outcomes:
Locations:
city: Los Angeles
country: United States
facility: Children's Center for Cancer and Blood Diseases, Children's Hospital Los Angeles
state: California
city: Boston
country: United States
facility: Children's Hospital Boston
state: Massachusetts
city: Boston
country: United States
facility: Dana-Farber Cancer Institute
state: Massachusetts
city: Brno
country: Czechia
facility: Fakultni nemocnice Brno
city: Brno
country: Czechia
facility: FN Brno
city: Brno
country: Czechia
facility: Masarykuv onkologicky ustav
city: Marseille cedex 5
country: France
facility: CHU de La Timone, Hopital enfants
city: Marseille cedex 5
country: France
facility: Hopital d'Enfants de la Timone
city: Marseille cedex 5
country: France
facility: Hopital de la Timone
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: 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.
citation: 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.