Clinical Trial Evaluating the Combination of Vandetanib and Dasatinib During and After Radiation Therapy (RT) in Children With Newly Diagnosed Diffuse Intrinsic Pontine Glioma (DIPG)

Diffuse Intrinsic Pontine Glioma Clinical Trial

Official title:

Phase I Study of the Combination of Vandetanib and Dasatinib Administered During and After Radiation Therapy in Children With Diffuse Intrinsic Pontine Glioma

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00996723
• Other study ID #: SJBG09
• Secondary ID: NCI-2011-01152
• Status: Completed
• Phase: Phase 1
• First received: October 15, 2009
• Last updated: April 3, 2015
• Start date: October 2009
• Est. completion date: June 2014

Study information

• Verified date: April 2015
• Source: St. Jude Children's Research Hospital
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial Summary

This is a Phase I clinical trial evaluating the combination of vandetanib and dasatinib during and after radiation therapy (RT) in children with newly diagnosed diffuse intrinsic pontine glioma (DIPG).

Description:

This trial will estimate the maximum safe dose of vandetanib and dasatinib which can be administered during the 6 weeks of local RT in children with newly diagnosed DIPG.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: June 2014
• Est. primary completion date: April 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Months to 21 Years

Eligibility

Inclusion Criteria:

1. Age must be = 18 months and < 21 years

2. Diagnosis of DIPG or high-grade glioma originating from the brainstem.

3. Lansky (for research participants = 16 years) or Karnofsky (for research participants > 16 years) performance score = 40 at the time of study enrollment

4. Adequate organ function at the time of study enrollment as follows:

• Bone marrow: ANC = 1,000/µL, platelet count = 100,000/µL (transfusion independent), hemoglobin concentration = 8g/dL (may be transfused)

• Renal: Serum creatinine concentration < 2x the institutional normal values for age or GFR > 70ml/min/1.73m2

• Hepatic: Total bilirubin concentration < 1.5x the institutional upper limit of normal for age; SGPT < 5x the institutional upper limit of normal; albumin = 2 g/dL

5. Electrocardiogram (EKG) with an average QTc interval < 450 msec. If a research participant has QTc interval = 450 msec on screening EKG, the screening EKG may be repeated twice (at least 24 hours apart). The average QTc interval from the three screening EKGs must be < 450 msec in order for the research participant to be eligible for the study. Research participants with abnormal serum electrolytes and a QTc interval = 450 msec should have a repeat EKG repeated once the concentration of serum electrolyte is corrected

6. Female research participants of childbearing age must not be pregnant (confirmed by serum or urine pregnancy test within 1 week of treatment start) or breast-feeding.

7. Female research participants of childbearing age and male research participants of child fathering potential must agree to use safe contraceptive methods

Exclusion Criteria:

1. Metastatic disease

2. Use of enzyme-inducing anticonvulsants

3. Research participants who received any other type of anticancer treatment

4. Research participants with uncontrolled infection

5. Research participants with any concomitant significant medical illness that in the investigator's opinion cannot be adequately controlled with appropriate therapy, or that would impair the evaluation of side effects related to this treatment, alter drug metabolism or the tolerance to this treatment

6. QTc interval prolongation with other medications that required discontinuation of that medication

7. Research participants with any history of cardiac arrhythmias or congenital long QT syndrome

8. Use of any concomitant medication that may cause QT interval prolongation and/or induce Torsades de Pointes

9. Hypertension defined as systolic and/or diastolic blood pressure > 95th percentile for age, height and gender, or blood pressure > 140/90 for research participants = 18 years of age. If hypertension is detected, blood pressure values < 95th in two separate occasions need to be documented before registration. Body surface = 1.8m2 for research participants enrolled on dosage levels 2, 3, and 4

Study Design

Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Diffuse Intrinsic Pontine Glioma
• Glioma

Intervention

Drug:
• vandetanib and dasatinib
Two oral investigational agents (vandetanib [VEGFR2, RET, and EGFR inhibitor] and dasatinib [bcr-abl, PDGFRA and B, src, lck, yes, and c-kit inhibitor] will be administered during and after local RT, which is the only standard therapy for children with DIPG.

Locations

Country	Name	City	State
United States	St. Jude Children's Research Hospital	Memphis	Tennessee

Sponsors (4)

Lead Sponsor	Collaborator
St. Jude Children's Research Hospital	AstraZeneca, The Cure Starts Now Foundation, Tyler's Treehouse

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	To estimate the maximum tolerated dose (MTD) of the combination of vandetanib and dasatinib administered concurrently with RT in pediatric research participants with newly diagnosed DIPG		April 2012	Yes
Secondary	To determine the toxicities associated with the chronic use of vandetanib and dasatinib		July 2012	Yes
Secondary	To characterize the pharmacokinetics of vandetanib and dasatinib in pediatric research participants		July 2012	No
Secondary	To evaluate the influence of specific polymorphisms (e.g., CYP3A4/5) on the pharmacokinetics of vandetanib and dasatinib administered in combination		July 2012	No
Secondary	To explore the association between plasma angiogenic factors and response to current therapy		July 2012	No
Secondary	To evaluate the pharmacodynamics of dasatinib in target receptors and pathways in peripheral mononuclear cells		July 2012	No
Secondary	To describe the research participants' and parents' perspective of the quality of life of children with newly diagnosed DIPG enrolled on this phase I trial		July 2012	No
Secondary	To describe the quality of life of parents of pediatric research participants with newly diagnosed DIPG enrolled on this phase I trial		July 2012	No

External Links

•   Clinical Trials Open at St. Jude
•   St. Jude Children's Research Hospital