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

NCT02015065 | Completed Phase 2 Results FDA Drug

• 2 other identifiers: 13020813-C-0208
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

Background:

• Some people with wild-type gastrointestinal stromal tumors (WT-GIST) have a deficiency in one of their proteins called succinate dehydrogenase (SDH). Vandetanib is a cancer drug that has been approved to treat thyroid cancer and has been used with some success in other tumors that have a similar loss of SDH. Researchers want to see if this drug can also decrease tumor growth in people with WT-GIST. Objectives:
• To test whether the study drug will benefit people with WT-GIST. Eligibility:
• Adults and children 3 years old and older with WT-GIST. Design:
• Researchers will test participants tumor tissue to confirm it is the wild type of GIST.
• Participants will be screened with a medical history, physical exam, and blood tests. They will also have electrical recording of the heart (Eastern Cooperative Oncology Group (ECOG)) and scans of the tumor.
• Participants will take the study drug in 28-day cycles. Their doctor will decide how many cycles they can complete.
• They will take the study drug once every day and record it in a diary.
• On Day 14, they will also visit their doctor to look for side effects.
• Before cycles 2, 3 and 4, participants will have a physical exam, urine tests, blood pressure check, and blood tests. These tests will then be done periodically for as long as they are in the study.
• Before cycle 4, scans will be done to check the size of the cancer. Most of these will be repeated every 3-6 cycles.
• When they stop taking the study drug, participants will return to the clinic for a physical exam and blood tests.

Conditions

GIST

Keywords

GIST; Small Molecule; Mesenchymal Tumor; Receptor Tyrosine Kinase; Survival

Outcome Measures

Primary Outcomes (1)

• Number of Participants With a Clinical Activity-radiographic Response

  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.

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

Secondary Outcomes (4)

• Count of Participants With Serious and Non-serious Adverse Events

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

• Percentage of Participants Overall Survival

  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.

• Progression Free-Survival

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

• Maximum Standardized Uptake Value (SUVmax) on Fluorodeoxyglucose Positron Emission Tomography (FDG-PET)

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

Study Arms (2)

Vandetanib in Children

EXPERIMENTAL

Children with measurable localized or metastatic wt-GIST

Drug: Vandetanib

Vandetanib in Adults

EXPERIMENTAL

Adults with measurable localized or metastatic wt-GIST

Drug: Vandetanib

Interventions

Vandetanib DRUG

Vandetanib administered orally once per day continuously using a 28 day cycle until disease progression or unacceptable toxicity

Vandetanib in Adults; Vandetanib in Children

Eligibility Criteria

• Age: 3 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Age:
• greater than or equal to 3 years of age and Body Surface Area (BSA) greater than or equal to 0.5 m(2)
• Diagnosis
• Histologically or cytologically confirmed Gastrointestinal Stromal Tumors (GIST) by the Laboratory of Pathology, National Cancer Institute (NCI).
• Absence of Kit and platelet derived growth factor receptor alpha (PDGFRA) mutation confirmed in a Clinical Laboratory Improvement Amendments (CLIA) certified laboratory.
• Participants must have measurable disease as defined in Response Evaluation Criteria in Solid Tumors (RECIST (v1.1) as the presence of at least one lesion not previously irradiated, that can be accurately measured at baseline greater than or equal to 10mm in the longest diameter (except lymph nodes which must have short axis greater than or equal to 15 mm) with computed tomography (CT) or magnetic resonance imaging (MRI) and which is suitable for accurate repeated measurements.
• Prior therapy:
• There are no standard chemotherapy regimens known to be effective for wt-GIST. Therefore, previously untreated participants are eligible if their tumor(s) are measurable.
• Participants must be at least 4 weeks from prior surgical procedures and surgical incisions must be healed.
• Participants must have had their last fraction of external beam radiation therapy at least 4 weeks prior to enrollment.
• Participants must have had their last dose of cytotoxic chemotherapy at least 28 days prior to enrollment, their last dose of biological therapy, such as biological response modifiers (e.g., cytokines), immunomodulatory agents, vaccines, differentiating agents, used to treat their cancer at least 7 days prior to enrollment, their last dose of a monoclonal antibody at least 30 days prior to enrollment, and their last dose of any investigational agent at least 30 days prior to enrollment.
• Participants must have received their last dose of short acting colony stimulating factor, such as filgrastim or sargramostim at least 72 hours prior to enrollment and their last dose of long-acting colony stimulating factors, such as PEG-filgrastim at least 7 days prior to enrollment.
• Participants must have recovered from the acute toxic effects of prior therapy to a grade 1 (Common Terminology Criteria in Adverse Events (CTCAE v.4.0)) level prior to enrollment (does not apply to alopecia).
• Performance Status: Lansky (for participants 10 years of age or younger) or Karnofsky (for participants older than 10 years) performance score greater than 50
• Patients must have normal organ and marrow function as defined below:

You may not qualify if:

• Presence of any of the following will prevent a subject from participation:
• Pregnant or breast feeding females because vandetanib may be harmful to the developing fetus or nursing infant and has been found to be embryotoxic, fetotoxic and teratogenic in rats.
• Subjects who are receiving any other investigational agents or who have received an investigational agent within 28 days prior to enrollment (does not apply to participation in survival follow up), or who have previous exposure to vandetanib.
• Presence of hypertension: Diastolic blood pressure above the 95% for age in children (Appendix 2) and \> 160 mmHg systolic or \>100 mmHg diastolic in adults on at least 2 of 3 measurements with an appropriate-size cuff who are unable to achieve blood pressure control with optimal anti-hypertensive therapy. Patients who are treated with antihypertensive medications with good response are eligible.
• History of Cardiac Disorder:
• Participants with a history of arrhythmia (multifocal premature ventricular contractions, bigeminy, trigeminy, ventricular tachycardia, uncontrolled atrial fibrillation, left bundle branch block) that is symptomatic or requires treatment (except for controlled atrial fibrillation).
• History of any significant cardiac event (e.g. myocardial infarction), superior vena cava syndrome, New York Heart Association (NYHA) classification of heart disease greater than or equal 2 within 12 weeks before starting treatment, or presence of cardiac disease that in the opinion of the Investigator increases the risk of ventricular arrhythmia.
• Participants with a history of congenitally prolonged corrected QT interval (QTc), a first degree relative with unexplained sudden death under 40 years of age, or a measured QTcB (Bazetts correction) longer than 480 msec on electrocardiography (ECG). ECGs should be performed after correction of electrolyte abnormalities. Participants with a prolonged QTcB should have a repeat ECG twice, at least 24 hour apart, and the average of the 3 QTcBs should not exceed 480 msec. History of QT prolongation associated with other medications that required discontinuation of that medication.
• Participants receiving a medication that has a known risk of QTc prolongation or is associated with Torsades de Pointes or any prohibited medications, concomitantly or within 14 days (28 days for levomethadyl) of enrollment.
• Impairment of gastrointestinal function or gastrointestinal disease that may significantly alter the absorption of vandetanib as evidenced by uncontrolled nausea, vomiting or diarrhea and/or current need for parenteral support with iron or Vitamin B.
• Other clinically severe or uncontrolled systemic illness or any concurrent condition that in the view of the principal investigator could compromise the participant's ability to tolerate vandetanib or could compromise study procedures or endpoints, including interstitial lung disease, drug-induced interstitial disease, radiation pneumonitis which required steroid treatment or any evidence of clinically active interstitial lung disease.
• Unstable brain metastases or spinal cord compression that requires treatment, unless the treatment ended at least 4 weeks before starting treatment and the condition has been stable without steroid treatment for at least 10 days.
• Major surgery (includes surgery that carries significant risk of blood loss, extended periods of general anesthesia, or requires at least an overnight hospital admission) within 28 days before starting treatment.
• Involvement in the planning and/or conduct of the study.
• Previous enrollment in the present study.

Sponsors & Collaborators

• National Cancer Institute (NCI): lead

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Interventions

vandetanib

Results Point of Contact

• Title: Dr. Brigitte Widemann
• Organization: National Cancer Institute

widemanb@nih.gov

240-760-6203

Study Officials

• Brigitte C Widemann, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: December 14, 2013
• First Posted: December 19, 2013
• Study Start: December 14, 2013
• Primary Completion: May 4, 2016
• Study Completion: December 10, 2019
• Last Updated: March 30, 2020
• Results First Posted: July 23, 2019

Record last verified: 2020-03

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)