A Phase 1/2 interventional study of Vandetanib in Medullary Thyroid Carcinoma, Multiple Endocrine Neoplasia Type 2A and Multiple Endocrine Neoplasia Type 2B, sponsored by National Cancer Institute (NCI). Completed at 1 site in United States. Open to participants aged 5 Years to 18 Years. Per ClinicalTrials.gov, last updated 2020-12-22.
Sponsored by National Cancer Institute (NCI) · Phase 1/2, Interventional, and Treatment
Background:
Objectives:
Eligibility:
-Children and adolescents 5 to 18 years of age with MTC whose tumor cannot be surgically removed or has grown back after treatment or has metastasized (spread beyond the thyroid gland).
Design:
BACKGROUND:
Hereditary medullary thyroid carcinoma (MTC), which is a rare calcitonin-producing tumor arising from the parafollicular C cells of the thyroid, is often a manifestation of multiple endocrine neoplasia (MEN) types 2A and 2B and can be detected in children as young as five years in MEN 2A and one year in those with MEN 2B
MEN results from an activating mutation in the rearranged during transfection (RET) proto-oncogene resulting in a constitutively activated receptor tyrosine kinase (RTK)
Vandetanib is an orally bioavailable multi-RTK inhibitor that blocks the mutant RET gene product and has anti-tumor activity in adults with hereditary MTC
OBJECTIVES:
To assess the activity of vandetanib in children and adolescents with hereditary MTC using Response Evaluation Criteria in Solid Tumors (RECIST) (primary endpoint), tumor biomarkers and tumor-related diarrhea
To assess the safety and tolerance of vandetanib in children and adolescents at a dose equivalent to the recommended dose in adults
To assess the pharmacokinetics of vandetanib at steady state in children and adolescents
Secondary objectives include monitoring progression-free and overall survival, assessing RET, epidermal growth factor receptor (EGFR), Vascular endothelial growth factor (VEGFR) and somatostatin receptor expression in archival tumor tissue, assessing changes in deoxyribonucleic acid (DNA) mutations in RET in tumor tissue vs germ line in PBMC and after treatment; assessing gene expression and gains/losses of DNA in tumor tissue at baseline, during treatment and at the time of progression; establishment of pediatric MTC cell lines sensitive and resistant cells lines in vitro
ELIGIBILITY:
Children and adolescents 5 to 18 years of age (inclusive) with unresectable, recurrent or metastatic hereditary medullary thyroid carcinoma
Measurable disease by RECIST (Response Evaluation Criteria in Solid Tumors)
DESIGN:
Vandetanib will be administered as a once daily dose, continuously (1 cycle equals 28 days) at a dose of 150 mg,m(2), per day
To ensure the safety of the adult dose in children and adolescents, a limited intra-patient dose escalation will be performed in the initial cohort of patients, with older patients (13 to18 yrs) being studied before younger patients (5 to12 yrs)
Patients wil be enrolled at a dose of 100mg, m(2), per day (180 mg per day in adults) for two 28 day cycles and escalated to 150 mg, m(2), per day (270 mg, per day in adults) on cycle 3, if dose limiting toxicity was not observed at the lower dose. If the 150mg, m(2), per day dose level is tolerable on cycles 3 and 4, all subsequent patients will be enrolled at this dose level
Pharmacokinetics of vandetanib will be studied at steady state at the end of cycle 2 and trough levels will be obtained prior to the second dose on cycle 1, and on day 1 of cycles 2-5.
Responsible of measurable tumors will be assessed by RECIST. Biomarker and clinical response will also be monitored. Twenty one patients will be studied to determine if the response rate in children and adolescents with hereditary MTC is consistent with the 28 percent objective response rate in adults
6,741 studies on the registry are indexed under Carcinoma; 1,161 are open to participants now.
This study's enrollment of 17 is below the median of 45 across 5,170 interventional studies indexed under Carcinoma.
Browse Carcinoma studies →National Cancer Institute (NCI) is the lead sponsor of 3,506 studies on the registry; 334 are open to participants now.
Of its 402 completed or terminated interventional studies of FDA-regulated products, 365 (91%) have results posted.
Counted across the registry records on this site, refreshed daily.
Age: Participants must be 5 to 18 years of age, inclusive. The first cohort of 3 to 6 participants enrolled on the trial will be at least 13 years of age.
Diagnosis: Hereditary (Multiple endocrine neoplasia, type 2A (MEN 2A) or Multiple endocrine neoplasia, type 2B (MEN 2B) medullary thyroid carcinoma (histologically confirmed) that is unresectable, recurrent or metastatic. Participants must have previously had a characteristic germline mutation in the rearranged during transfection (RET) proto-oncogene documented. Results of the germline mutation testing will be obtained from the referring institution.
Participants must have measurable disease as defined in Response Evaluation Criteria in Solid Tumors (RECIST) as the presence of at least one lesion that can be accurately measured in at least one dimension with longest diameter of at least 20 mm using conventional techniques or at least 10 mm with spiral computed tomography (CT) scan. Superficial (easily palpable) lymph nodes will be considered measurable.
Participants must be able to take one of the oral formulations of vandetanib.
Prior therapy: There are no standard chemotherapy regimens known to be effective for medullary thyroid carcinoma (MTC). Therefore, previously untreated participants are eligible if their tumor(s) are not surgically resectable.
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 polyethylene glycol (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 for Adverse Events (CTCAE) v.3.0) level prior to enrollment.
Performance Status: Lansky (for participants 10 years of age or younger) or Karnofsky (for participants older than 10 years) performance score greater than 50
Concomitant Medications:
Participants who have previously had a thyroidectomy should be on thyroid hormone replacement therapy.
Hematological Function: The peripheral absolute neutrophil count must be at least 1,500 micro liters and the platelet count must be at least 100,000 micro liters within 72 hours prior to enrollment.
Coagulation: Prothrombin Time (PT) and Partial Thromboplastin Time (PTT) must not be more than 1.5 x ULN within 72 hours prior to enrollment. PT and PTT should drawn by venipuncture, rather than from a central venous catheter when feasible.
Hepatic Function:
Bilirubin must not be more than 1.5 x ULN and the aspartate aminotransferase (AST) and alanine aminotransferase (ALT) must not be more than 2.5 x ULN within 72 hours prior to enrollment. AST and ALT may be up to 5 x ULN within 72 hours prior to enrollment in participants with hepatic metastases.
Renal Function: Participants must have an age-adjusted normal serum creatinine or a creatinine clearance of at least 60 ml/min/1.73 m\^2.
Birth Control: Participants of child-bearing or child-fathering potential must be willing to use a medically effective form of birth control, which includes abstinence, while taking vandetanib and for 2 months after the last dose.
Negative pregnancy test for women of childbearing potential.
Informed Consent: Participants who are 18 years of age or legal guardians of participants who are younger than 18 years must sign an informed consent for the Pediatric Oncology Branch (POB) Screening Protocol prior to participating in studies required to determine eligibility for this trial. After confirmation of eligibility, participants or legal guardians of minor participants must sign an informed consent document for this trial, indicating that they are aware of the investigational nature of the proposed treatment, the risks and benefits of participating and the alternatives to participating.
EXCLUSION CRITERIA:
Pregnant or breast feeding females because the anti-angiogenic properties of vandetanib may be harmful to the developing fetus or nursing infant.
Participants with pheochromocytoma as evidenced by elevated plasma free metanephrines.
Electrolytes: Participants with a serum potassium less than 3.5 mmol/L or a serum calcium or magnesium below the lower limits of normal. Correction of these electrolyte abnormalities with supplements is allowed.
Cardiac:
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)
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 QTc (Bazett's correction) longer than 480 msec on electrocardiogram (ECG). ECGs should be performed after correction of electrolyte abnormalities. Participants with a prolonged QTc should have a repeat ECG at least 24 hour after the first, and the mean of the 2 QTcs should not exceed 480 msec.
Participants who experienced QTc prolongation with other medications requiring discontinuation of that medication.
Participants receiving a medication that has a known risk of QTc prolongation within 14 days (28 days for levomethadyl) of enrollment.
Hypertension: Diastolic blood pressure above the 95% for age on at least 2 of 3 measurements with an appropriate-size cuff or patients who are currently taking anti-hypertensive therapy.
Other clinically severe or uncontrolled systemic illness that could compromise the participants ability to tolerate vandetanib or could compromise study procedures or endpoints.
Vandetanib administered as a once daily dose, continuously (1 cycle = 28 days) at a dose of 150 mg/m\^2/day.
Drug: Vandetanib
once daily continuously (28 day cycles)
Also known as: Caprelsa
Maximum Tolerated Dose (MTD)
The MTD is the highest dose of Vandetanib tolerated at which a participant experienced a dose limiting toxicity (DLT) during the first two cycles of drug.
Time frame: During Cycle 1 and Cycle 2, approximately 56 days
Overall Percentage of Participants With an Objective Response Defined as a Complete Response (CR) or Partial Response (PR)
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive Disease is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
Time frame: Patients were evaluated for response after every 2 cycles x 4 (prior to cycles 1, 3, 5, 7, and 9) and then after every 4 cycles X 1 (prior to cycle 13) and then every 6 cycles (prior to cycle 19, 25, 31, etc). Response was followed for an median of 59 mon
Number of Participants With an Increase or Decrease in Carcinoembryonic Antigen (CEA) Biomarker Response
Blood was collected from participants and measured with an Axsym Analyzer then Immulite CEA method and assessed by the following response criteria. Partial Response (PR) is a ≥50% decrease in the CEA level relative to the baseline level, confirmed with a repeat CEA level at least 4 weeks apart. Progression (P) is a ≥50% increase in the CEA relative to the prior value on 2 consecutive measurements at least 4 weeks apart. The patient must have been taking vandetanib for 4 weeks prior to the first measurements and must have continued to take the drug through the time that the second measurement was drawn. Stable (S) is a \<50% increase or decrease in CEA level relative to the baseline level.
Time frame: Every 2 cycles x 4 (prior to cycles 1, 3, 5, 7 and 9), prior to cycle 13, and then every 6 cycles (prior to cycle 19, 25, 31, etc). Patients were followed for response for a median of 59 months.
Percent Change in Calcitonin (CTN) Biomarker Response After Cycle 1
Blood was collected from participants and measured with an Chemiluminescence immunoassay. Calcitonin upper limit of normal is \<10 pg/mL. A decline in CTN is defined as a ≥50% increase (e.g. tumor growth or progression) in the CTN level after treatment in cycle 1.
Time frame: Cycle 1 (28 days)
Area Under the Concentration Time Curve (AUC 0-24h)
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
Time frame: Cycle 1, Pre-dose and then 1, 2, 4, 6, 8, 10 and 24 hour post dose.
Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0)
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). 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.
Time frame: Date treatment consent signed to date off study, approximately 142 months and 8 days.
Number of Participants With a Dose Limiting Toxicity (DLT)
Hematologic Dose-Limiting Toxicity (H-DLT) is: Neutrophil count below 1,000/μL (grade 3) on 2 consecutive measurements drawn at least 72 hours apart OR a single neutrophil count below 500/μL (grade 4); Platelet count below 50,000/μL (grade 3) on 2 consecutive measurements drawn at least 72 hours apart OR a single platelet count below 25,000/μL (grade 4); A platelet transfusion administered when platelet count is below 50,000/μL is dose limiting thrombocytopenia, unless the transfusion is being administered for perioperative coverage; Grade 3 or 4 decrease in hemoglobin that can be corrected to at least 8.0 g/dl (grade 2) by transfusion of red blood cells is not a dose-limiting toxicity. Grade 3 or 4 hemolysis is a dose-limiting toxicity if it is judged to be vandetanib-related. Non-Hematologic Dose-Limiting Toxicity is any grade 3 or higher non-hematologic toxicity, with some exceptions such as Grade 3 nausea that is controlled by symptomatic treatment with anti-emetics.
Time frame: up to Cycle 3 (each Cycle is 28 days)
| Milestone | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg |
|---|---|---|---|---|---|---|---|---|---|
| Started | 5 | 1 | 5 | 1 | 1 | 1 | 1 | 1 | 1 |
| Completed | 2 | 0 | 0 | 1 | 0 | 0 | 1 | 0 | 0 |
| Not completed | 3 | 1 | 5 | 0 | 1 | 1 | 0 | 1 | 1 |
| Withdrew: Transferred to another protocol | 2 | 1 | 3 | 0 | 1 | 0 | 0 | 0 | 0 |
| Withdrew: Getting vandetanib via the rems program | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| Withdrew: Disease progression on study | 0 | 0 | 2 | 0 | 0 | 1 | 0 | 0 | 0 |
The MTD is the highest dose of Vandetanib tolerated at which a participant experienced a dose limiting toxicity (DLT) during the first two cycles of drug.
| mg/m^2/day | All Participants |
|---|---|
| Maximum Tolerated Dose (MTD) | 100 |
Response was assessed by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete Response is disappearance of all target lesions. Partial Response is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as reference the baseline sum LD. Stable Disease is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking as reference the smallest sum LD since the treatment started. Progressive Disease is at least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.
| percentage of participants | All Participants |
|---|---|
| Overall Percentage of Participants With an Objective Response Defined as a Complete Response (CR) or Partial Response (PR) | 59 (33 to 82) |
Blood was collected from participants and measured with an Axsym Analyzer then Immulite CEA method and assessed by the following response criteria. Partial Response (PR) is a ≥50% decrease in the CEA level relative to the baseline level, confirmed with a repeat CEA level at least 4 weeks apart. Progression (P) is a ≥50% increase in the CEA relative to the prior value on 2 consecutive measurements at least 4 weeks apart. The patient must have been taking vandetanib for 4 weeks prior to the first measurements and must have continued to take the drug through the time that the second measurement was drawn. Stable (S) is a \<50% increase or decrease in CEA level relative to the baseline level.
| Participants | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg |
|---|---|---|---|---|---|---|---|---|---|
| <50% decrease/<50% increase | 1 | 0 | 1 | 1 | 0 | 0 | 0 | 0 | 0 |
| >50% increase | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 |
| ≥50% decrease | 3 | 1 | 3 | 0 | 1 | 0 | 1 | 0 | 1 |
| Not Evaluable (NE) | 1 | 0 | 0 | 0 | 0 | 1 | 0 | 1 | 0 |
Blood was collected from participants and measured with an Chemiluminescence immunoassay. Calcitonin upper limit of normal is \<10 pg/mL. A decline in CTN is defined as a ≥50% increase (e.g. tumor growth or progression) in the CTN level after treatment in cycle 1.
| percent change in calcitonin | All Participants |
|---|---|
| Percent Change in Calcitonin (CTN) Biomarker Response After Cycle 1 | -59 (-84 to -34) |
The AUC is a measure of the serum concentration of the drug over time. It is used to characterize drug absorption.
| mcg*h/mL | All Participants |
|---|---|
| Area Under the Concentration Time Curve (AUC 0-24h) | 16 (13.5 to 23.3) |
Here is the number of participants with serious and non-serious adverse events assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0). 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.
| Participants | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg |
|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With Serious and Non-serious Adverse Events Assessed by the Common Terminology Criteria for Adverse Events (CTCAE v3.0) | 5 | 1 | 5 | 1 | 1 | 1 | 1 | 1 | 1 |
Hematologic Dose-Limiting Toxicity (H-DLT) is: Neutrophil count below 1,000/μL (grade 3) on 2 consecutive measurements drawn at least 72 hours apart OR a single neutrophil count below 500/μL (grade 4); Platelet count below 50,000/μL (grade 3) on 2 consecutive measurements drawn at least 72 hours apart OR a single platelet count below 25,000/μL (grade 4); A platelet transfusion administered when platelet count is below 50,000/μL is dose limiting thrombocytopenia, unless the transfusion is being administered for perioperative coverage; Grade 3 or 4 decrease in hemoglobin that can be corrected to at least 8.0 g/dl (grade 2) by transfusion of red blood cells is not a dose-limiting toxicity. Grade 3 or 4 hemolysis is a dose-limiting toxicity if it is judged to be vandetanib-related. Non-Hematologic Dose-Limiting Toxicity is any grade 3 or higher non-hematologic toxicity, with some exceptions such as Grade 3 nausea that is controlled by symptomatic treatment with anti-emetics.
| Participants | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg |
|---|---|---|---|---|---|---|---|---|---|
| Number of Participants With a Dose Limiting Toxicity (DLT) | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Collected over Date treatment consent signed to date off study, approximately 142 months and 8 days.. Non-serious events are listed at a 0% frequency threshold.
| Group | Deaths | Serious | Other |
|---|---|---|---|
| Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | 0/5 (0%) | 2/5 (40%) | 5/5 (100%) |
| Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Vandetanib 100 mg/m^2 | 0/5 (0%) | 1/5 (20%) | 4/5 (80%) |
| Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | 0/1 (0%) | 1/1 (100%) | 1/1 (100%) |
| Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | 0/1 (0%) | 0/1 (0%) | 1/1 (100%) |
| Event | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg |
|---|---|---|---|---|---|---|---|---|---|
| Pain::GallbladderHepatobiliary disorders | 0/5 | 0/1 | 0/5 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders | 0/5 | 0/1 | 1/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| AnorexiaGastrointestinal disorders | 0/5 | 0/1 | 1/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Carbon monoxide diffusion capacity (DL(co))Respiratory, thoracic and mediastinal disorders | 1/5 | 0/1 | 0/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| DehydrationGastrointestinal disorders | 0/5 | 0/1 | 1/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Gastritis (including bile reflux gastritis)Gastrointestinal disorders | 0/5 | 0/1 | 1/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Gastrointestinal - Other (Gastroenteritis)Gastrointestinal disorders | 0/5 | 0/1 | 1/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Liver dysfunction/failure (clinical)Hepatobiliary disorders | 1/5 | 0/1 | 0/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Obstruction, GI::GallbladderGastrointestinal disorders | 1/5 | 0/1 | 0/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Pain::Abdomen NOSGastrointestinal disorders | 1/5 | 0/1 | 0/5 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| Event | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg |
|---|---|---|---|---|---|---|---|---|---|
| ALT, SGPT (serum glutamic pyruvic transaminase)Metabolism and nutrition disorders | 4/5 | 0/1 | 3/5 | 1/1 | 1/1 | 1/1 | 1/1 | 1/1 | 1/1 |
| AST, SGOT(serum glutamic oxaloacetic transaminase)Metabolism and nutrition disorders | 3/5 | 1/1 | 3/5 | 0/1 | 0/1 | 1/1 | 0/1 | 1/1 | 1/1 |
| Albumin, serum-low (hypoalbuminemia)Metabolism and nutrition disorders | 2/5 | 1/1 | 3/5 | 1/1 | 0/1 | 1/1 | 0/1 | 0/1 | 0/1 |
| Alkaline phosphataseMetabolism and nutrition disorders | 5/5 | 1/1 | 3/5 | 1/1 | 0/1 | 1/1 | 0/1 | 1/1 | 0/1 |
| Allergic rhinitis (including sneezing, nasal stuffiness, postnasal drip)Immune system disorders | 3/5 | 1/1 | 0/5 | 1/1 | 1/1 | 0/1 | 1/1 | 0/1 | 0/1 |
| Allergy/ImmunologyImmune system disorders | 0/5 | 0/1 | 0/5 | 1/1 | 0/1 | 0/1 | 0/1 | 0/1 | 0/1 |
| AnorexiaGastrointestinal disorders | 3/5 | 1/1 | 3/5 | 1/1 | 1/1 | 1/1 | 0/1 | 0/1 | 0/1 |
| Bicarbonate, serum-lowMetabolism and nutrition disorders | 3/5 | 1/1 | 3/5 | 0/1 | 1/1 | 0/1 | 0/1 | 1/1 | 0/1 |
| Bruising (in absence of Grade 3 or 4 thrombocytopenia)Skin and subcutaneous tissue disorders | 0/5 | 0/1 | 1/5 | 0/1 | 0/1 | 1/1 | 0/1 | 0/1 | 0/1 |
| CPK (creatine phosphokinase)Metabolism and nutrition disorders | 2/5 | 0/1 | 0/5 | 0/1 | 1/1 | 0/1 | 0/1 | 1/1 | 0/1 |
| Age, Categorical(Participants) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| <=18 years | 5 | 1 | 5 | 1 | 1 | 1 | 1 | 1 | 1 | 17 |
| Between 18 and 65 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| >=65 years | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Age, Continuous(years) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Mean | 15.14 ± 2.07 | 15.4 ± 0 | 12.52 ± 2.81 | 16.7 ± 0 | 12.1 ± 0 | 17.3 ± 0 | 13.2 ± 0 | 11.3 ± 0 | 16.8 ± 0 | 14.50 ± 2.44 |
| Sex: Female, Male(Participants) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Female | 4 | 1 | 3 | 1 | 0 | 0 | 0 | 0 | 0 | 9 |
| Male | 1 | 0 | 2 | 0 | 1 | 1 | 1 | 1 | 1 | 8 |
| Ethnicity (NIH/OMB)(Participants) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Hispanic or Latino | 2 | 0 | 1 | 1 | 0 | 0 | 0 | 1 | 0 | 5 |
| Not Hispanic or Latino | 3 | 1 | 4 | 0 | 1 | 1 | 1 | 0 | 1 | 12 |
| Unknown or Not Reported | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Race (NIH/OMB)(Participants) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| American Indian or Alaska Native | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Asian | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Native Hawaiian or Other Pacific Islander | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Black or African American | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 1 | 1 |
| White | 5 | 1 | 4 | 1 | 1 | 1 | 1 | 1 | 0 | 15 |
| More than one race | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Unknown or Not Reported | 0 | 0 | 1 | 0 | 0 | 0 | 0 | 0 | 0 | 1 |
| Region of Enrollment(participants) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| United States | 5 | 1 | 5 | 1 | 1 | 1 | 1 | 1 | 1 | 1 |
| Baseline Performance Status(scores on a scale) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Median | 100 (90 to 100) | 80 (80 to 80) | 80 (80 to 100) | 80 (80 to 80) | 100 (100 to 100) | 90 (90 to 90) | 100 (100 to 100) | 100 (100 to 100) | 100 (100 to 100) | 100 (80 to 100) |
| Calcitonin (CTN) at Enrollment(pg/mL) | Vandetanib: First 100 mg/m^2, Then 150 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 67mg | Vandetanib 100 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 100mg | Vandetanib:First 100mg/m^2, Then 63mg, 42, 21, 42, & 21mg/m^2 | Vandetanib: First 100 mg/m^2, Then 70 mg/m^2 | Vandetanib: First 100mg/m^2, Then 150mg/m^2, Followed by 200mg | Vandetanib:First 100mg/m^2, Then 150mg, 100, 150, 100, 150mg | Vandetanib: First 150mg/m^2, Then 100mg/m^2, Followed by 150mg | Total |
|---|---|---|---|---|---|---|---|---|---|---|
| Patient 1 | 0 | 18,300 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 2 | 67,100 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 3 | 0 | 0 | 4,500 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 4 | 0 | 0 | 25,900 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 5 | 0 | 0 | 18,900 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 6 | 0 | 0 | 0 | 4,600 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 7 | 0 | 0 | 0 | 0 | 0 | 2,000 | 0 | 0 | 0 | 0 |
| Patient 8 | 0 | 0 | 0 | 0 | 3,500 | 0 | 0 | 0 | 0 | 0 |
| Patient 9 | 500 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 10 | 0 | 0 | 57,800 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 11 | 0 | 0 | 0 | 0 | 0 | 0 | 13,300 | 0 | 0 | 0 |
| Patient 12 | 6,900 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 13 | 24,200 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 14 | 21,400 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
| Patient 15 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 800 | 0 | 0 |
| Patient 16 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 47.700 | 0 |
| Patient 17 | 0 | 0 | 16,064 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
1 further baseline measures are reported on the registry.
Documents are hosted by the registry — open the source record to download them.
Plan to share: Yes — We wish to share IPD via two citations.
Supporting information: Study protocol, Sap, Icf
This study is completed, as verified in Dec 2020. You cannot join it, but the record below documents what was studied.
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