Trial Outcomes & Findings for A Trial of ZD6474, Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery (NCT NCT01183559)

Last Updated: 2021-01-22

Results Overview

To determine the maximum tolerated dose (MTD) of Vandetanib given concurrently with chemotherapy and radiation therapy followed by surgery (esophagectomy)evaluated by the frequency, severity and duration of adverse events that occur during treatment and for four weeks following surgery as measured by serial blood tests, electrocardiograms and physical assessments

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

9 participants

Primary outcome timeframe

Within 4 weeks of initiation of chemo/radiation therapy

Results posted on

2021-01-22

Participant Flow

Recruitment Details: Patients were accrued between March 2009 and August 2010 at Fox Chase Cancer Center outpatient medical oncology clinics.

Resectable stage II-III esophageal and GE junction carcinomas;staging by CT and PET scans, endoscopic ultrasound. Patients with a history or presence of ventricular dysfunction, ventricular or atrial arrhythmias; heart block; congestive heart failure; recent myocardial infarction,unstable angina, or uncontrolled hypertension were excluded

Participant milestones

Participant milestones
Measure	Vandetanib All patients were treated with vandetanib with dose escalation from 100 mg (dose level 1) to 200 mg (dose level 2) orally daily for the duration of radiation therapy
Overall Study STARTED	9
Overall Study COMPLETED	9
Overall Study NOT COMPLETED	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

A Trial of ZD6474, Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Vandetanib n=9 Participants All patients were treated with vandetanib with dose escalation from 100 mg (dose level 1) to 200 mg (dose level 2) orally daily for the duration of radiation therapy
Age, Continuous Years	58 years n=93 Participants
Sex: Female, Male Female	0 Participants n=93 Participants
Sex: Female, Male Male	9 Participants n=93 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=93 Participants
Race (NIH/OMB) Asian	0 Participants n=93 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=93 Participants
Race (NIH/OMB) Black or African American	0 Participants n=93 Participants
Race (NIH/OMB) White	9 Participants n=93 Participants
Race (NIH/OMB) More than one race	0 Participants n=93 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=93 Participants
Tumor site type Middle third	1 Participants n=93 Participants
Tumor site type Lower third	6 Participants n=93 Participants
Tumor site type GE junction	2 Participants n=93 Participants
Primary Site of Disease Esophagus	2 Participants n=93 Participants
Primary Site of Disease Gastroesophageal junction	7 Participants n=93 Participants

PRIMARY outcome

Timeframe: Within 4 weeks of initiation of chemo/radiation therapy

Outcome measures

Outcome measures
Measure	Vandetanib n=9 Participants All patients were treated with Vandetanib 100 mg QD (6 patients) or 200 mg daily (3 patients) orally daily during the conventional 3D-guided conformal radiation therapy plus chemotherapy with carboplatin (AUC 5) on days 1 and 29, paclitaxel 50 mg/m2 i.v. weekly on days 1, 8, 15, 22, 29; and continuous infusion of 5-fluorouracil at 225 mg/m2 for 96 hours Monday-Friday during the radiation.
Maximum Tolerated Dose of Vandetanib	100 milligrams

SECONDARY outcome

Timeframe: Within 4 weeks of initiation of chemo/radiation therapy

To determine the safety and tolerability of Vandetanib when given in combination with chemotherapy and radiation therapy as evaluated by serial blood tests, electrocardiograms, and physical assessments during therapy and for four weeks following surgery

Outcome measures

Outcome measures
Measure	Vandetanib n=9 Participants All patients were treated with Vandetanib 100 mg QD (6 patients) or 200 mg daily (3 patients) orally daily during the conventional 3D-guided conformal radiation therapy plus chemotherapy with carboplatin (AUC 5) on days 1 and 29, paclitaxel 50 mg/m2 i.v. weekly on days 1, 8, 15, 22, 29; and continuous infusion of 5-fluorouracil at 225 mg/m2 for 96 hours Monday-Friday during the radiation.
The Number of Participants With Adverse Events	2 Participants

Adverse Events

Vandetanib

Serious events: 1 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Vandetanib n=9 participants at risk All patients were treated with vandetanib with dose escalation from 100 mg (dose level 1) to 200 mg (dose level 2) orally daily for the duration of radiation therapy
Gastrointestinal disorders Aortic-enteric fistula	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death

Other adverse events

Other adverse events
Measure	Vandetanib n=9 participants at risk All patients were treated with vandetanib with dose escalation from 100 mg (dose level 1) to 200 mg (dose level 2) orally daily for the duration of radiation therapy
Gastrointestinal disorders Anorexia	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Investigations ALT-SGPT	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Investigations AST-SGPT	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Investigations Leukocyte, total WBC	22.2% 2/9 • Number of events 2 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Psychiatric disorders Mood alteration, Depression	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Investigations Neutrophills, ANC/AGC	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Gastrointestinal disorders Pain, upper abdomen	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Investigations Sodium, serum low (hyponatremia)	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Nervous system disorders Syncope	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Gastrointestinal disorders Mucositis	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death
Gastrointestinal disorders Stomach-Bronchial fistula	11.1% 1/9 • Number of events 1 • From initiation of Vandetanib therapy through 6 months Adverse events evaluated for severity and relationship to therapy using a grading system in which Grade 3 = severe, Grade 4 = life-threatening or disabling and Grade 5 = death

Additional Information

Igor Astsaturov, MD, PhD, Assistant Professor, Medical Oncology

Phone: 215 728-3135

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place