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Cancer of the EsophagusPhase 1NCT01183559

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

A Phase 1 study testing Vandetanib, 5 Fluorouracil (FU) and Carboplatin in people with Cancer of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Fox Chase Cancer Center at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 years and older
What is being tested?
Vandetanib, 5 Fluorouracil (FU) and Carboplatin
Could I receive a placebo?
No, everyone receives an active treatment
How many people
9 participants
Where
1 siteUnited States
Study dates
7 Aug 2008to Aug 2011
Phase
Phase 1
Are there results?
Yes, posted in the registrySummary in the doctors' view

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 years and older
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 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.

Who cannot join

  • 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.
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  • 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.
  • 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/mm^3 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

Trial locations and contacts

1 site in 1 country.

United States1 site

  • Fox Chase Cancer Center

    Philadelphia, Pennsylvania, 19111

Other trials in United States

About this study

Official title: Induction Therapy for Locally Advanced, Resectable Cancer of the Esophagus, Gastroesophageal (GE) Junction and Gastric Cancer: A Phase I Trial of ZD6474 (Zactima, Vandetanib), Paclitaxel, Carboplatin, 5-Fluorouracil, and Radiation Therapy Followed by Surgery

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

Read the detailed description

Epidermal Growth Factor Receptor (EGFR) is known to be an important prognostic factor for patients with esophageal cancer-overexpression is associated with a worse prognosis. Review of the literature demonstrates presence of EGFR expression in up 90% of cases of esophageal cancer. Additionally, Vascular Endothelial Growth factor (VEGF) is commonly overexpressed in esophageal cancer (especially adenocarcinoma) and is linked to the transition from Barrett's esophagus to invasive adenocarcinoma. Esophageal cancers with overexpression of VEGF are associated with a worse prognosis and poorer response to conventional chemoradiation.

Therefore, we feel it would be valuable to add an inhibitor of EGFR and VEGFR to the therapy of esophageal cancer to increase the rate of pathologic complete response and thus improve overall survival. In current trials of ZD6474 in combination with chemotherapy, the dose has been 300mg. We will perform a phase I trial in which we will dose-escalate ZD6474 to determine if this drug is tolerable in combination with cytotoxic chemotherapy and external beam radiation therapy. This would be the first trial in humans in which f these three modalities would be combined. We will determine the maximum tolerated dose of ZD6474 in this small trial and then hope to perform a larger phase II trial, perhaps in the context of the Radiation Therapy Oncology Group (RTOG).

Being tested
Vandetanib, 5 Fluorouracil (FU), Carboplatin, Paclitaxel, External Beam Radiation Therapy (RT)
Medical subject headings
Esophageal Neoplasms, Stomach Neoplasms

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • VandetanibDrug

    Also called ZD6474, Zactima

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

  • 5 Fluorouracil (FU)Drug

    Also called 5-FU

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

  • CarboplatinDrug

    Carboplatin AUC=5 days 1 and 29 during radiation therapy

  • PaclitaxelDrug

    Also called Taxol

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

  • External Beam Radiation Therapy (RT)Radiation

    Also called XRT, RT

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

Study groups in NCT01183559
Study groupRoleWhat they receive
VandetanibOtherVandetanib 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.
Receives: Drug: Vandetanib; Drug: 5 Fluorouracil (FU); Drug: Carboplatin; Drug: Paclitaxel; Radiation: External Beam Radiation Therapy (RT)

What is being measured

The primary outcome is the main question the study is designed to answer.

  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

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

Secondary outcomes (1)

  1. The Number of Participants With Adverse Events

    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

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

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted17 Aug 2010 (estimated)
  2. Study start7 Aug 2008
  3. Primary completionNov 2010
  4. Study completionAug 2011

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
9 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01183559
Sponsor's protocol ID
FCCC IRB 07-017
Status last verified
Jan 2021
First submitted
13 Aug 2010
Last updated
22 Jan 2021
Data monitoring committee
Yes

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Vandetanib, 5 Fluorouracil (FU) and Carboplatin in people with Cancer of the Esophagus and Adenocarcinoma of the Gastroesophageal Junction, run by Fox Chase Cancer Center at 1 site in United States.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 7 inclusion and 22 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 22 Jan 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Yes. Results are posted in the registry (first posted 22 Jan 2021). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Maximum Tolerated Dose of Vandetanib (time frame: Within 4 weeks of initiation of chemo/radiation therapy). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT01183559.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jan 2021.

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