Phase II Trial of Vandetanib in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors
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|ClinicalTrials.gov Identifier: NCT02015065|
Recruitment Status : Active, not recruiting
First Posted : December 19, 2013
Last Update Posted : December 14, 2018
-Some people with wild-type gastrointestinal stromal tumors (WT-GIST) have a deficiency in one of their proteins called 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.
-To test whether the study drug will benefit people with WT-GIST.
-Adults and children 3 years old and older with WT-GIST.
- 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 (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 physicial exam and blood tests.
|Condition or disease||Intervention/treatment||Phase|
|GIST||Drug: Vandetanib||Phase 2|
- Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract, resistant to cytotoxic chemotherapy and radiation therapy. KIT and PDGFRA mutations have been identified as tumor initiating events in 85% of adult patients with GIST, but 85% of GISTs in pediatric patients lack KIT and PDGFRA mutations (wild-type) and imatinib is not as effective in eliciting objective responses.
- Recent work in the Pediatric and Wild-Type (wt) GIST Clinic at the NCI led to the identification of succinate dehydrogenase (SDH) germline mutations in 12% patients with wt-GIST (6/34). SDH protein expression evaluated using immunohistochemistry (IHC) was markedly decreased or absent in 18/18 patients with pediatric wt-GIST. Thus the majority of wt-GIST are SDH-deficient. Vandetanib (ZACTIMA; ZD6474; AstraZeneca) is an oral small molecule antineoplastic drug that inhibits VEGFR2, EGFR, and RET-dependent signaling. Preliminary preclinical data demonstrate marked growth inhibition of SDH-mutant/deficient renal cell carcinoma cell lines when treated with vandetanib.
-Primary: To assess the clinical activity (radiographic response RECIST v1.1) of vandetanib in children and adults with wt-GIST using RECIST (v1.1).
-Adults and children with measurable localized or metastatic wt-GIST confirmed in a CLIA laboratory will be eligible for trial participation. Patients must have measurable disease by RECISTv1.1 and adequate organ function.
- This phase II trial will determine whether daily oral vandetanib is active in patients with wt-GIST. Vandetanib activity will be assessed primarily by radiographic response of measurable disease using RECISTv1.1.
- Vandetanib will be administered orally once daily continuously in the absence of toxicity or disease progression, using a 28-day cycle.
- Patients will be carefully monitored for toxicity and response. A small, optimal two-stage phase II design with a target response rate of 25% will be used. Nine evaluable patients will be enrolled initially. If 1 or more of the first 9 have a response, then accrual would continue until a total of 24 patients have enrolled. If there are 3 or more responses in 24 (12.5% or more) patients, then this would be sufficiently interesting activity to warrant further study.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||9 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||Phase II Trial of Vandetanib (ZD6474, Caprelsa(R) in Children and Adults With Wild-Type Gastrointestinal Stromal Tumors|
|Study Start Date :||December 14, 2013|
|Actual Primary Completion Date :||May 4, 2016|
|Estimated Study Completion Date :||August 31, 2023|
Adults and children with measurable localized or metastatic wt-GIST
Vandetanib administered orally once per day continuously using a 28 day cycle until disease progression or unacceptable toxicity
- Clinical activity-radiographic response. [ Time Frame: Every 3-6 cycles (1 cycle = 28 days) ]Efficacy
- To assess the safety and toxicity of vandetanib. [ Time Frame: Every cycle (28 days) ]
- To evaluate overall and progression free survival [ Time Frame: At time of death ]
- To evaluate the utility of FDG-PET in disease characterization and response evaluation in patients >/= 15 years of age [ Time Frame: Day 3-6 in the first cycle ]
- To assess SDH expression, RET, EGFR, VEGFR and somatostatin receptor expression on archival tissue [ Time Frame: By end of study ]
- To describe health related quality of life in patients >/= 8 years of age [ Time Frame: At start of therapy, 3 months and at off treatment ]
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02015065
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Brigitte C Widemann, M.D.||National Cancer Institute (NCI)|