Trial Outcomes & Findings for Vandetanib to Treat Advanced Kidney Cancer (NCT NCT01372813)

Last Updated: 2015-10-23

Results Overview

Clinical response is the best response recorded from the start of treatment until disease progression. Clinical response is assessed by the Response Evaluation in Solid Tumors (RECIST) criteria. A partial response (PR) is at least a 30% decrease in the sum of the longest diameter (LD) of target lesions, taking as a reference the baseline sum LD. A complete response (CR) is the disappearance of all target lesions.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

3 participants

Primary outcome timeframe

12 months

Results posted on

2015-10-23

Participant Flow

Trial only accrued 3 participants.

Participant milestones

Participant milestones
Measure	Clear Cell Renal Carcinoma Patients Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Overall Study STARTED	3
Overall Study COMPLETED	3
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Vandetanib to Treat Advanced Kidney Cancer

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Clear Cell Renal Carcinoma Patients n=3 Participants Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Age, Categorical <=18 years	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	3 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants
Age, Continuous	58.8 years STANDARD_DEVIATION 5.43 • n=5 Participants
Sex: Female, Male Female	1 Participants n=5 Participants
Sex: Female, Male Male	2 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	3 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants
Region of Enrollment United States	3 participants n=5 Participants

PRIMARY outcome

Timeframe: 12 months

Outcome measures

Outcome measures
Measure	Clear Cell Renal Carcinoma Patients n=3 Participants Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Number of Participants With a Clinical Response (Partial Response (PR) + Clinical Response (CR))	0 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Not enough samples for meaningful analysis.

Plasma VEGFR and VEGFR2 would have been measured using the (enzyme-linked immunosorbent assay)ELISA at baseline and specified timepoints following initiation of therapy.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Not enough samples for meaningful analysis.

CEP cell concentrations are calculated as a percentage of the total number of mononuclear cells or as the number of cells/microliter of whole blood after an evaluation of a minimum of 10\^5 cellular events, and preferably 10\^6 cellular events.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Progression free survival is defined as the time from initiation of treatment to either progression or death. RECIST evaluates tumor response. Changes in only the largest diameter (unidimensional measurement) of the tumor lesions are used in the RECIST criteria. For detailed information about RECIST, see the protocol Link module.

Outcome measures

Outcome measures
Measure	Clear Cell Renal Carcinoma Patients n=3 Participants Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Progression-free Survival as Defined by the Response Evaluation Criteria in Solid Tumors (RECIST) Criteria	55 Days Interval 51.0 to 111.0

SECONDARY outcome

Timeframe: 11.5 months

Here are the number of participants with adverse events. For the detailed list of adverse events see the adverse event module.

Outcome measures

Outcome measures
Measure	Clear Cell Renal Carcinoma Patients n=3 Participants Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Number of Participants With Adverse Events	3 Participants

SECONDARY outcome

Timeframe: 12 months

Population: Not enough samples for meaningful analysis.

CEC cell concentrations are calculated as a percentage of the total number of mononuclear cells or as the number of cells/microliter of whole blood after an evaluation of a minimum of 10\^5 cellular events, and preferably 10\^6 cellular events.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Flow dynamics within specific tumor sites will be evaluated based on the results of the DCE-MRI obtained first without contrast enhancement and then after contrast enhancement. The parameter to be measured is the forward contrast transfer rate (Ktrans), the reverse contrast transfer rate (Kep), and/or the extravascular extracellular space volume fraction (Ve). Flow dynamics are a measure of blood flow changes in the tumor and are determined using the parameters previously defined (Ktrans, Kep, etc.).

Outcome measures

Outcome measures
Measure	Clear Cell Renal Carcinoma Patients n=2 Participants Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Number of Participants With Vandetanib (ZD6474) Effects on Tumor Vascular Flow and Permeability Using Dynamic Contrast Enhanced Magnetic Resonance Imaging (DCE-MRI)	0 Participants with changes

SECONDARY outcome

Timeframe: 12 months

Population: Not enough samples for meaningful analysis.

Components of the VEGF and EGFR pathways were to be evaluated using Western blot analysis at baseline and specified timepoints following initiation of therapy when tumor tissue was available.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Not enough samples for meaningful analysis.

Tumor tissue sections were to be stained with hematoxylin and eosin (H and E) and endothelial cell markers at baseline and specified timepoints following initiation of therapy (when tumor tissue was available)

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: 12 months

Population: Not enough samples for meaningful analysis.

If an adequate number of responses were seen, the relation of these responses to the presence/absence of inactivating VHL mutations in tumor tissue would have been assessed.

Outcome measures

Outcome data not reported

Adverse Events

Clear Cell Renal Carcinoma Patients

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Clear Cell Renal Carcinoma Patients n=3 participants at risk Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Gastrointestinal disorders Diarrhea	33.3% 1/3 • Number of events 1 • 11.5 months

Other adverse events

Other adverse events
Measure	Clear Cell Renal Carcinoma Patients n=3 participants at risk Clear cell renal cancer is a highly vascular tumor characterized by mutations in the von Hippel-Lindau (VHL) gene in the majority of patients, an alteration that leads to overexpression vascular endothelial growth factor (VEGF) as well as other genes such as transforming growth factor-alpha, platelet derived growth factor and glucose transporter 1. Patients received ZD6474 300 mg/day by mouth daily on days 1-28.
Investigations ALT, SGPT (serum glutamic pyruvic transaminase)	33.3% 1/3 • Number of events 1 • 11.5 months
Metabolism and nutrition disorders Albumin, serum-low (hypoalbuminemia)	33.3% 1/3 • Number of events 1 • 11.5 months
Investigations Alkaline phosphatase	33.3% 1/3 • Number of events 1 • 11.5 months
Investigations Bicarbonate, serum-low	33.3% 1/3 • Number of events 1 • 11.5 months
Investigations Creatinine	33.3% 1/3 • Number of events 1 • 11.5 months
Gastrointestinal disorders Dry mouth/salivary gland (xerostomia)	33.3% 1/3 • Number of events 1 • 11.5 months
Metabolism and nutrition disorders Glucose, serum-high (hyperglycemia)	33.3% 1/3 • Number of events 1 • 11.5 months
Blood and lymphatic system disorders Hemoglobin	33.3% 1/3 • Number of events 1 • 11.5 months
Vascular disorders Hypertension	33.3% 1/3 • Number of events 1 • 11.5 months
Metabolism and nutrition disorders Magnesium, serum-high (hypermagnesemia)	33.3% 1/3 • Number of events 1 • 11.5 months
Metabolism and nutrition disorders Magnesium, serum-low (hypomagnesemia)	33.3% 1/3 • Number of events 1 • 11.5 months
Gastrointestinal disorders Nausea	33.3% 1/3 • Number of events 2 • 11.5 months
Nervous system disorders Neurology - Other (Specify, lightheadedness)	33.3% 1/3 • Number of events 1 • 11.5 months
Musculoskeletal and connective tissue disorders Pain::Neck	33.3% 1/3 • Number of events 1 • 11.5 months
Metabolism and nutrition disorders Phosphate, serum-low (hypophosphatemia)	33.3% 1/3 • Number of events 1 • 11.5 months
Investigations Prolonged QTc interval	33.3% 1/3 • Number of events 1 • 11.5 months
Skin and subcutaneous tissue disorders Rash: acne/acneiform	33.3% 1/3 • Number of events 1 • 11.5 months

Additional Information

Marston Linehan, M.D.

National Cancer Institute, National Institutes of Health

Phone: 301-496-6353

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place