A Trial of ZD6474 (Zactima), Paclitaxel, Carboplatin, 5-Fluorouracil, and XRT Followed by Surgery

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01183559
Recruitment Status : Unknown
Verified February 2011 by Fox Chase Cancer Center.
Recruitment status was:  Recruiting
First Posted : August 17, 2010
Last Update Posted : February 10, 2011
Information provided by:
Fox Chase Cancer Center

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

Condition or disease Intervention/treatment Phase
Cancer of the Esophagus, Gastroesophageal Junction or Stomach Drug: ZD6474 (Zactima) Phase 1

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 12 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Induction Therapy for Locally Advanced, Resectable Cancer of the Esophagus, GE Junction and Gastric Cancer: A Phase I Trial of ZD6474 (Zactima), Paclitaxel, Carboplatin, 5-Fluorouracil, and XRT Followed by Surgery (IRUSZACT0064)
Study Start Date : August 2008

Intervention Details:
    Drug: ZD6474 (Zactima)
    Other Names:
    • Paclitaxel
    • Carboplatin
    • 5-FU
    • Radiation therapy

Primary Outcome Measures :
  1. Maximum tolerated dose [ Time Frame: Within 4 weeks of initiation of chemo/radiation therapy ]
    To determine the maximum tolerated dose (MTD) of ZD6474 given concurrently with 5- FU, paclitaxel, carboplatin, and radiation therapy followed by esophagectomy.

Secondary Outcome Measures :
  1. Safety and tolerability [ Time Frame: WIthin 4 weeks of initiation of chemo/radiation therapy ]
    To determine the safety and tolerability of ZD 6474 when given in combination with cytotoxic chemotherapy and radiation therapy

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

Inclusion criteria:

  • Histologically documented carcinoma of the esophagus, gastroesophageal junction, or stomach for which chemo/radiation therapy is appropriate.
  • Potentially resectable esophageal, GE junction carcinoma, or stomach carcinoma
  • ECOG PS = 0-2
  • No evidence of distant metastases
  • Age 18 or greater
  • Signed informed consent
  • Willingness to practice adequate contraception in women of childbearing potential. Contraception must be continued for one month following discontinuation of the study drugs. Female patients of childbearing potential (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.

Exclusion criteria:

  • 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 (see Appendix A) 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 (CTCAE grade 3) 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 (see Appendix B)
  • 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.
  • Uncontrollable diarrhea that may affect the ability of the patient to absorb ZD 6474 or tolerate side-effects.

Laboratory results:

  • Adequate bone marrow function as defined by granulocyte count < 1500/mm3 and platelet count < 100,000
  • Serum bilirubin >1.5x the upper limit of reference range (ULRR)
  • Serum creatinine >1.5 x ULRR or creatinine clearance < 50 mL/minute (calculated by Cockcroft-Gault formula.)
  • Potassium < 4.0 mmol/L despite supplementation; serum calcium (ionized or adjusted for albumin,) or magnesium out of normal range despite supplementation.
  • Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) > 2.5 X ULRR

Information from the National Library of Medicine

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 identifier (NCT number): NCT01183559

Contact: Igor Astsaturov, M.D., Ph.D. 215-728-2500

United States, Pennsylvania
Fox Chase Cancer Center Recruiting
Philadelphia, Pennsylvania, United States, 19111
Contact: Igor Astsaturov, M.D., Ph.D.    215-728-2500   
Principal Investigator: Walter Scott, M.D.         
Sponsors and Collaborators
Fox Chase Cancer Center
Principal Investigator: Igor Astsaturov,, M.D., Ph.D. Fox Chase Cancer Center

Responsible Party: Igor Astsaturov, M.D., Fox Chase Cancer Center Identifier: NCT01183559     History of Changes
Obsolete Identifiers: NCT00462033
Other Study ID Numbers: FCCC IRB 07-017
First Posted: August 17, 2010    Key Record Dates
Last Update Posted: February 10, 2011
Last Verified: February 2011

Additional relevant MeSH terms:
Esophageal Neoplasms
Gastrointestinal Neoplasms
Digestive System Neoplasms
Neoplasms by Site
Head and Neck Neoplasms
Digestive System Diseases
Esophageal Diseases
Gastrointestinal Diseases
Albumin-Bound Paclitaxel
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action
Antimetabolites, Antineoplastic
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs