A Phase I/II Study of Sunitinib in Young Patients with Advanced Gastrointestinal Stromal Tumor

• Register: EUCTR
• Last refreshed on: 2 August 2021
• Main ID: EUCTR2011-002008-33-ES
• Date of registration: 16/01/2012
• Prospective Registration: Yes
• Primary sponsor: Pfizer, S.L.U.
• Public title: A Phase I/II Study of Sunitinib in Young Patients with Advanced Gastrointestinal Stromal Tumor
• Scientific title: A PHASE I/II STUDY OF SUNITINIB IN YOUNG PATIENTS WITH ADVANCED GASTROINTESTINAL STROMAL TUMOR
• Date of first enrolment: 03/04/2012
• Target sample size: 30
• Recruitment status: Not Recruiting
• URL: https://www.clinicaltrialsregister.eu/ctr-search/search?query=eudract_number:2011-002008-33
• Study type: Interventional clinical trial of medicinal product
• Study design: Controlled: no; Randomised: no; Open: no; Single blind: no; Double blind: no; Parallel group: no; Cross over: no; Other: no; If controlled, specify comparator, Other Medicinial Product: no; Placebo: no; Other: no
• Phase: Human pharmacology (Phase I): yes Therapeutic exploratory (Phase II): yes Therapeutic confirmatory - (Phase III): no Therapeutic use (Phase IV): no

Countries of recruitment

Argentina, Austria, Brazil, Canada, Chile, Czech Republic, Egypt, France, Germany, Hungary, Italy, Jordan, Mexico, Norway, Poland, Portugal, Slovakia, Spain, Turkey, United Kingdom, United States

Contacts

• Name: Clincal Trials.gov Call Center
• Affiliation: Pfizer Inc.

• Name: Clincal Trials.gov Call Center
• Affiliation: Pfizer Inc.

Key inclusion & exclusion criteria

Inclusion criteria:
Patient eligibility should be reviewed and documented by an appropriately qualified member of the investigator?s study team before patients are included in the study.
Patients must meet all of the following inclusion criteria to be eligible for enrollment into the study:
1. Histological diagnosis of GIST;
2. KIT genotype (consent for testing sufficient if previous disease progression/intolerance to imatinib);
3. Patients with KIT mutant GIST must have demonstrated either disease progression or intolerance to imatinib mesylate;
4. Age 6 - <21 years;
5. Unresectable without major morbidity, metastatic or recurrent GIST;
6. Measurable (per Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1) or evaluable disease;
7. Resolution of all acute toxic effects of prior cancer treatment, radiotherapy or surgical procedure to NCI CTCAE v4.0 grade ?1;
8. ECOG Performance Status 0-2 (for patients ?11 years of age) or Lansky ?50% (for patients <11 years);
9. Adequate organ function determined within 14 days prior to enrollment, defined by:
? Peripheral absolute neutrophil count (ANC) ?1000/µL without growth factor support;
? Platelet count ?100,000/µL (transfusion independent, defined as not receiving platelet transfusions within a 7 days prior to enrollment);
? Hemoglobin ?10 g/dL;
? Total bilirubin ?1.5 x upper limit of normal (ULN) for age;
? ALT (SGPT) ?110 U/L;
? Serum albumin ?2.0 g/dL;
? Serum amylase and lipase <1.5 x ULN;
? Serum creatinine based on age/gender as follows:
Age Maximum Serum Creatinine
(mg/dL)
Male Female
6 to <10 years 1 1
10 to <13 years 1.2 1.2
13 to <16 years 1.5 1.4
?16 years 1.7 1.4
The threshold creatinine values in this table were derived from the Schwartz formula for estimating GFR (Schwartz et al. J. Peds, 106:522, 1985) utilizing child length and stature data published by the CDC.
? Blood Pressure (BP) < the 95th percentile for age, height and gender
? Cardiac shortening fraction or ejection fraction greater than the lower limit of normal (LLN) (institutional norm).
10. Evidence of a personally signed and dated informed consent (and where applicable, assent) document indicating that the patient (or a legally acceptable representative) has been informed of all pertinent aspects of the study;
11. Patients (including legal guardian for minors) who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.

Male and female patients of childbearing potential who are sexually active must agree to use a highly effective method of contraception throughout the study and for 30 days after the last after the last sunitinib treatment. A patient is of childbearing potential if, in the opinion of the investigator, he/she is biologically capable of having children and is sexually active
Are the trial subjects under 18? yes
Number of subjects for this age range: 15
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 15
F.1.3 Elderly (>=65 years) no
F.1.3.1 Number of subjects for this age range

Exclusion criteria:
Patients presenting with any of the following will not be included in the study:
1. Current treatment with another investigational agent and/or systemic anti-cancer therapy within 4 weeks before starting sunitinib treatment;
2. Prior sunitinib treatment;
3. Prior therapy with known risk for cardiovascular complications, eg, prior radiation therapy that included the heart (cardiac silhouette) and/or craniospinal radiation;
Patients with prior anthracycline exposure may be included if the total cumulative exposure was ?150mg/m2;
4. Concomitant treatment with any drug having proarrhythmic potential (terfenadine, quinidine, procainamide, disopyramide, sotalol, probucol, bepridil, haloperidol, risperidone, indapamide and flecainide);
5. Prior diagnosis of cardiac disease, including, but not limited to:
? Ongoing cardiac dysrhythmias of NCI CTCAE v4.0 ? grade 2, atrial fibrillation of any grade;
? QTc interval >450 msec for males or >470 msec for females;
? Hypertension that cannot be controlled by medications;
? Any of the following within the 12 months prior to starting study treatment: congestive heart failure, cerebrovascular accident including transient ischemic attack or pulmonary embolism.
6. Grade ?3 hemorrhage within 4 weeks prior to study entry;
7. Current treatment with therapeutic doses of coumarin derivative anticoagulants such as warfarin or anti vitamin K agents;
8. Concurrent administration of strong cytochrome P450-3A (CYP3A4) inhibitor(s) and/or inducer(s) within 7 and 12 days prior to study entry, respectively;
9. Prior radiation to >25% of the bone marrow;
10. Patients with history of allergic reaction attributed to sunitinib or any component of sunitinib capsules;
11. Pregnant females; breastfeeding females; males and females of childbearing potential; males and females of childbearing potential not using highly effective contraception or not agreeing to continue highly effective contraception for 30 days after last dose of investigational product; males and females of childbearing potential not using two (2) methods of highly effective contraception or not agreeing to continue two (2) methods of highly effective contraception for 30 days after last dose of investigational product;
12. Active infection, or receiving antiretroviral therapy for HIV disease;
13. Patients who are investigational site staff members or relatives of those site staff members or patients who are Pfizer employees directly involved in the conduct of the trial;
14. Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the patient inappropriate for entry into this study.


Age minimum:
Age maximum:
Gender:
Female: yes
Male: yes

Health Condition(s) or Problem(s) studied

Therapeutic area: Diseases [C] - Cancer [C04]

Pediatric Gastro Intestinal Stromal Tumor (GIST)
MedDRA version: 14.1 Level: LLT Classification code 10062427 Term: Gastrointestinal stromal tumor System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)

Intervention(s)

Trade Name: Sutent
Pharmaceutical Form: Capsule
INN or Proposed INN: Sunitinib malate
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Other descriptive name: SU011248 L-Malate; SU010398; PHA-290940AD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 25-

Trade Name: Sutent
Pharmaceutical Form: Capsule
INN or Proposed INN: Sunitinib malate
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Other descriptive name: SU011248 L-Malate; SU010398; PHA-290940AD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 12.5-

Product Name: Sutent
Pharmaceutical Form: Capsule
INN or Proposed INN: Sunitinib malate
CAS Number: 341031-54-7
Current Sponsor code: SU011248
Other descriptive name: SU011248 L-Malate; SU010398; PHA-290940AD
Concentration unit: mg milligram(s)
Concentration type: equal
Concentration number: 6.25-

Primary Outcome(s)

Secondary Objective: - To investigate whether doses greater than the established pediatric MTD are tolerated in chemotherapy naive pediatric patients with GIST;
- To investigate the safety and tolerability of sunitinib in children and young adults with GIST;
- To investigate the anti tumor activity of sunitinib in children and young adults with GIST;
- To explore PK pharmacodynamic relationships with respect to safety and efficacy in children and young adults with GIST.

Main Objective: To characterize the plasma PK profile of sunitinib and its active metabolite SU012662 in children and young adults with advanced (defined as unresectable without major morbidity, metastatic or recurrent) GIST.

Primary end point(s): Pharmacokinetic parameters of sunitinib and its main active metabolite (SU012662) including total plasma exposure (AUC24) and oral clearance (CL/F).

Timepoint(s) of evaluation of this end point: Descriptive statistics for observed and dose-corrected (where appropriate) PK data will be reported for all patients with at least one PK observation by presenting the population size, arithmetic mean, standard deviation, percent coefficient of variation (CV%), median, minimum, maximum values at the end of the study.

Secondary Outcome(s)

Secondary end point(s): -Type, incidence, severity (graded by the National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events [CTCAE], Version 4.0 [v4.0]), timing, seriousness, and relatedness of adverse events and laboratory abnormalities;
-Objective response rate, duration of response, PFS and OS at 2 years after study enrollment;
-Pharmacokinetic pharmacodynamic relationships with respect to safety and efficacy in pediatric GIST

Timepoint(s) of evaluation of this end point: At the end of the study.

Secondary ID(s)

2011-002008-33-HU

A6181196

Source(s) of Monetary Support

Pfizer Inc., 235 East 42nd Street, New York, NY 10017

Ethics review

Status: Approved
Approval date: 15/03/2012
Contact:

Results

• Results available: Yes
• Date Posted: 25/02/2018
• Date Completed: 21/08/2017
• URL: https://www.clinicaltrialsregister.eu/ctr-search/trial/2011-002008-33/results