Trial Outcomes & Findings for Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors (NCT NCT02015065)

NCT ID: NCT02015065

Last Updated: 2020-03-30

Results Overview

Clinical activity will be assessed primarily by radiographic response of measurable disease using the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1. Complete Response is disappearance of all target lesions. Any pathological lymph nodes must have reduction in short axis to \<10 mm. Partial Response is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameters. Progressive Disease is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study); (Note: the appearance of one or more new lesions is also considered progressions). Stable Disease is neither sufficient shrinkage to qualify for Partial Response nor sufficient increase to qualify for Progressive Disease, taking as reference the smallest sum diameters while on study.

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

9 participants

Primary outcome timeframe

Every 3 cycles x4 and then every 6 cycles (1 cycle = 28 days) until removal from protocol therapy, an average of 12 months.

Results posted on

2020-03-30

Participant Flow

Due to lack of efficacy no participants were enrolled in Dose Level 150mg/m\^2 Vandetanib Pediatric Arm/Group.

Participant milestones

Participant milestones
Measure	200 mg Vandetanib Adult Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Overall Study STARTED	2	5	2
Overall Study COMPLETED	1	3	1
Overall Study NOT COMPLETED	1	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	200 mg Vandetanib Adult Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Overall Study Death on study	1	2	1

Baseline Characteristics

Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	200 mg Vandetanib Adult n=2 Participants Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=5 Participants Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric n=2 Participants Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.	Total n=9 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	2 Participants n=5 Participants	2 Participants n=4 Participants
Age, Categorical Between 18 and 65 years	2 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	7 Participants n=4 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants
Age, Continuous	24.5 years STANDARD_DEVIATION 3.0 • n=5 Participants	34.3 years STANDARD_DEVIATION 13.17 • n=7 Participants	13.2 years STANDARD_DEVIATION 2.12 • n=5 Participants	27.42 years STANDARD_DEVIATION 13.11 • n=4 Participants
Sex: Female, Male Female	1 Participants n=5 Participants	4 Participants n=7 Participants	2 Participants n=5 Participants	7 Participants n=4 Participants
Sex: Female, Male Male	1 Participants n=5 Participants	1 Participants n=7 Participants	0 Participants n=5 Participants	2 Participants n=4 Participants
Race/Ethnicity, Customized Not meeting definition for Hispanic or Latino	2 Participants n=5 Participants	5 Participants n=7 Participants	1 Participants n=5 Participants	8 Participants n=4 Participants
Race/Ethnicity, Customized Mexican, Puerto Rican, Cuban, Central or So. Amer.	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized Black or African American	1 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	1 Participants n=4 Participants
Race/Ethnicity, Customized White	1 Participants n=5 Participants	5 Participants n=7 Participants	0 Participants n=5 Participants	6 Participants n=4 Participants
Race/Ethnicity, Customized Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants	1 Participants n=4 Participants
Region of Enrollment United States	2 Participants n=5 Participants	5 Participants n=7 Participants	2 Participants n=5 Participants	9 Participants n=4 Participants

PRIMARY outcome

Timeframe: Every 3 cycles x4 and then every 6 cycles (1 cycle = 28 days) until removal from protocol therapy, an average of 12 months.

Outcome measures

Outcome measures
Measure	200 mg Vandetanib Adult n=2 Participants Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=5 Participants Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric n=2 Participants Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Number of Participants With a Clinical Activity-radiographic Response Complete Response	0 Participants	0 Participants	0 Participants
Number of Participants With a Clinical Activity-radiographic Response Partial Response	0 Participants	0 Participants	0 Participants
Number of Participants With a Clinical Activity-radiographic Response Stable Disease	1 Participants	2 Participants	1 Participants
Number of Participants With a Clinical Activity-radiographic Response Progressive Disease	1 Participants	3 Participants	1 Participants

SECONDARY outcome

Timeframe: Date treatment consent signed to date off study, approximately 32 months and 1 day.

The count of participants with serious and non-serious adverse events was assessed by the Common Terminology Criteria in Adverse Events (CTCAE v4.0). A non-serious adverse event is any untoward medical occurrence. A serious adverse event is an adverse event or suspected adverse reaction that results in death, a life threatening adverse drug experience, hospitalization, disruption of the ability to conduct normal life functions, congenital anomaly/birth defect or important medical events that jeopardize the patient or subject and may require medical or surgical intervention to prevent one of the previous outcomes mentioned.

Outcome measures

Outcome measures
Measure	200 mg Vandetanib Adult n=2 Participants Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=5 Participants Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric n=2 Participants Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Count of Participants With Serious and Non-serious Adverse Events	2 Participants	5 Participants	2 Participants

SECONDARY outcome

Timeframe: Overall survival was computed using the number of months from the date of on study to the date of death, an average of 12 months.

Overall survival is defined as the date of on-study to the date of death from any cause or last follow up.

Outcome measures

Outcome measures
Measure	200 mg Vandetanib Adult n=2 Participants Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=5 Participants Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric n=2 Participants Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Percentage of Participants Overall Survival	50 percentage of participants Interval 0.6 to 91.0	60 percentage of participants Interval 12.6 to 88.2	50 percentage of participants Interval 0.6 to 91.0

SECONDARY outcome

Timeframe: Patients will be evaluated approximately 60 days after last dose of investigational drug until removal of protocol therapy, an average of 12 months.

Progression free survival is defined as the time interval from start of treatment to documented evidence of disease progression. Disease progression was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and is at least a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5 mm. (Note: the appearance of one or more new lesions is also considered progressions).

Outcome measures

Outcome measures
Measure	200 mg Vandetanib Adult n=1 Participants Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=5 Participants Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric n=2 Participants Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Progression Free-Survival	4 Months Interval 0.6 to 91.0	5.1 Months Interval 1.8 to 22.5	13.4 Months Interval 2.7 to 24.1

SECONDARY outcome

Timeframe: Baseline and at a subsequent PET performed on or about day 3-6 of cycle 1

Population: Data were only collected from patients \>/= 15 years of age.

The maximum standardized uptake value (SUVmax) was used to measure the uptake of FDG-PET by the Gastrointestinal Tumors.

Outcome measures

Outcome measures
Measure	200 mg Vandetanib Adult n=1 Participants Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=3 Participants Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Maximum Standardized Uptake Value (SUVmax) on Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Baseline	22.4 g/mL Interval 22.4 to 22.4	21.4 g/mL Interval 15.6 to 30.7	—
Maximum Standardized Uptake Value (SUVmax) on Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) Day 3-6 of cycle 1	22.0 g/mL Interval 22.0 to 22.0	12.4 g/mL Interval 7.5 to 19.3	—

Adverse Events

200 mg Vandetanib Adult

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

300 mg Vandetanib Adult

Serious events: 4 serious events

Other events: 5 other events

Deaths: 2 deaths

Dose Level 100mg/m^2 Vandetanib Pediatric

Serious events: 0 serious events

Other events: 2 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	200 mg Vandetanib Adult n=2 participants at risk Initially patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If vandetanib was tolerated at 200mg daily the dose was increased to 300mg daily. Because of excessive toxicity at the 300mg daily dose the study was amended to maintain a dose of 200mg daily in patients 18 years and older after cycle 3.	300 mg Vandetanib Adult n=5 participants at risk Patients 18 years and older at the time of enrollment on this study will start vandetanib at a fixed dose of 200 mg once daily (QD) for cycles 1, 2, and 3. One cycle = 28 days. If Vandetanib was well tolerated: Cycles ≥4: 300 mg/dose	Dose Level 100mg/m^2 Vandetanib Pediatric n=2 participants at risk Patients younger than 18 years of age at the time of enrollment were started at a dose of 100 mg/m\^2 based on a dosing nomogram with a planned increase in the dose to 150mg/m\^2/day after the third cycle if the drug was tolerated. One cycle = 28 days.
Gastrointestinal disorders Abdominal pain	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	20.0% 1/5 • Number of events 1 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.
Vascular disorders Hypertension	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	20.0% 1/5 • Number of events 1 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.
Nervous system disorders Seizure	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	20.0% 1/5 • Number of events 1 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.
Gastrointestinal disorders Stomach pain	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	20.0% 1/5 • Number of events 1 • Date treatment consent signed to date off study, approximately 32 months and 1 day.	0.00% 0/2 • Date treatment consent signed to date off study, approximately 32 months and 1 day.

Other adverse events

Additional Information

Dr. Brigitte Widemann

National Cancer Institute

Phone: 240-760-6203

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place