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

NCT01183559 | Completed Phase 1 Results DMC

• 1 other identifier: FCCC IRB 07-017
• Study Type: interventional
• Target: 9
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of the study is to determine the most tolerable and safe dose of ZD6474 (Zactima, Vandetanib) when given with standard chemotherapy, radiation therapy and surgery in patients with cancer of the esophagus

Conditions

Cancer of the Esophagus; Adenocarcinoma of the Gastroesophageal Junction; Cancer of the Stomach

Outcome Measures

Primary Outcomes (1)

• Maximum Tolerated Dose of Vandetanib

  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

  Within 4 weeks of initiation of chemo/radiation therapy

Secondary Outcomes (1)

• The Number of Participants With Adverse Events

  Within 4 weeks of initiation of chemo/radiation therapy

Study Arms (1)

Vandetanib

OTHER

Vandetanib 100 mg (6 patients) or 200 mg (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.

Drug: Vandetanib; Drug: 5 Fluorouracil (FU); Drug: Carboplatin; Drug: Paclitaxel; Radiation: External Beam Radiation Therapy (RT)

Interventions

Vandetanib DRUG

Vandetanib 100mg orally escalating to doses of 200 mg daily 7 days a week until completion of radiation therapy

Also known as: ZD6474, Zactima

Vandetanib

5 Fluorouracil (FU) DRUG

5-FU 225 mg/m2/day continuous infusion over96 hours during radiation therapy

Also known as: 5-FU

Vandetanib

Carboplatin DRUG

Carboplatin AUC=5 days 1 and 29 during radiation therapy

Vandetanib

Paclitaxel DRUG

Paclitaxel 50 mg/m2 days 1, 8, 15, 22, 29 during radiation therapy

Also known as: Taxol

Vandetanib

External Beam Radiation Therapy (RT) RADIATION

External Beam Radiation Therapy(XRT)to a total dose of 4,500 centiGray (cGy) (180 cGy fractions daily) Monday through Friday for five weeks

Also known as: XRT, RT

Vandetanib

Eligibility Criteria

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

You may qualify if:

• Histologically documented carcinoma of the esophagus, gastroesophageal junction, or stomach for which chemo/radiation therapy is appropriate.
• Potentially resectable esophageal, Gastroesophageal junction carcinoma, or stomach carcinoma
• Eastern Cooperative Oncology Group Performance Status = 0-2
• No evidence of distant metastases
• Age 18 or greater
• Signed informed consent
• Willingness to practice adequate contraception in women of childbearing potential (WOCBP). Contraception must be continued for one month following discontinuation of the study drugs. Females who are WOCBP must have negative pregnancy test within 7 days of the first treatment. WOCBP includes any female who has experienced menarche and who has not undergone successful surgical sterilization (hysterectomy, bilateral tubal ligation, or bilateral oophorectomy) or is postmenopausal (defined as amenorrhea \>=12 consecutive months, or women on hormone replacement therapy (HRT) with documented plasma follicle-stimulating hormone (FSH) level \>35 mIU/mL). Even women who are using oral, implanted, or injectable contraceptive hormones or mechanical products (diaphragm, condoms, spermicides) to prevent pregnancy or practicing abstinence or where partner is sterile (e.g. vasectomy), should be considered to be WOCBP. Should a woman become pregnant or suspect she is pregnant while participating in this study, she should inform her treating physician immediately.

You may not qualify if:

• Previous radiation therapy to chest or upper abdomen.
• Evidence of severe or uncontrolled systemic disease or any concurrent condition which in the Investigator's opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
• Impaired cardiac function at baseline, including any of the following:
• Clinically significant cardiac event such as myocardial infarction; New York Heart Association (NYHA) classification of heart disease \>2 within 3 months before registration; or presence of cardiac disease that, in the opinion of the Investigator, increases the risk of ventricular arrhythmia.
• Inadequate pulmonary and cardiac function to tolerate surgery (see section 12): left ventricular ejection fraction \<45% and/or a positive stress test; or Forced Expiratory Volume (FEV1) of \<1.1 liters.
• History of arrhythmia (multifocal premature ventricular contractions (PVCs), bigeminy, trigeminy, ventricular tachycardia, or uncontrolled atrial fibrillation) which is symptomatic or requires treatment or asymptomatic sustained ventricular tachycardia. Atrial fibrillation, controlled on medication is not excluded.
• Previous history of QTc prolongation as a result from other medication that required discontinuation of that medication.
• Congenital long QT syndrome, or 1st degree relative with unexplained sudden death under 40 years of age.
• Presence of left bundle branch block (LBBB).
• QTc with Bazett's correction that is unmeasurable, or \>or= 480 msec on screening ECG. If a patient has QTc \>or= 480 msec on screening ECG, the screen ECG may be repeated twice (at least 24 hours apart). The average QTc from the three screening ECGs must be \<480 msec in order for the patient to be eligible for the study).
• Any concomitant medication that may cause QTc prolongation, induce Torsades de Pointes or induce CYP3A4 function
• Hypertension not controlled by medical therapy (systolic blood pressure greater than 160 mm Hg or diastolic blood pressure greater than 100 mm Hg)
• Women who are currently pregnant or breast feeding.
• Previous or current malignancies within the last 5 years, with the exception of cervical carcinoma in situ and adequately treated basal cell or squamous cell carcinoma of the skin
• Receipt of any investigational agents within 30 days prior to commencing study treatment.

Sponsors & Collaborators

• Fox Chase Cancer Center: lead
• AstraZeneca: collaborator

Study Sites (1)

Fox Chase Cancer Center

Philadelphia, Pennsylvania, 19111, United States

Location

MeSH Terms

Conditions

Esophageal Neoplasms; Stomach Neoplasms

Interventions

vandetanib; Fluorouracil; Carboplatin; Paclitaxel

Condition Hierarchy (Ancestors)

Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Head and Neck Neoplasms; Digestive System Diseases; Esophageal Diseases; Gastrointestinal Diseases; Stomach Diseases

Intervention Hierarchy (Ancestors)

Uracil; Pyrimidinones; Pyrimidines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Coordination Complexes; Organic Chemicals; Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Diterpenes; Terpenes

Limitations and Caveats

Study closed due to reaching the stated endpoint of determination of the phase II recommended and tolerated dose of Vandetanib

Results Point of Contact

• Title: Igor Astsaturov, MD, PhD, Assistant Professor, Medical Oncology
• Organization: Igor Astsaturov, MD, PhD, Assistant Professor, Medical Oncology

Igor.Astsaturov@fccc.edu

215 728-3135

Study Officials

• Igor Astsaturov,, M.D., Ph.D.

  Fox Chase Cancer Center

  PRINCIPAL INVESTIGATOR

Publication Agreements

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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 13, 2010
• First Posted: August 17, 2010
• Study Start: August 7, 2008
• Primary Completion: November 1, 2010
• Study Completion: August 1, 2011
• Last Updated: January 22, 2021
• Results First Posted: January 22, 2021

Record last verified: 2021-01

Locations

US (1)