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Phase I Trial of Vandetanib (ZD6474, Zactima) and Fulvestrant (Faslodex) as Third-Line Treatment of Advanced Non-Small Cell Lung Cancer

Phase 1
18 Years
Not Enrolling
Carcinoma, Non Small Cell Lung

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Trial Information

Phase I Trial of Vandetanib (ZD6474, Zactima) and Fulvestrant (Faslodex) as Third-Line Treatment of Advanced Non-Small Cell Lung Cancer

Current treatment for metastatic non-small cell lung cancer (NSCLC) is inadequate, with a
median survival of 8-12 months. Second-line therapy options include cytotoxic agents or
molecularly-targeted agents such as erlotinib. Nevertheless, only 7-9% of patients will
respond to standard second-line treatment. Treatment-related side effects from cytotoxic
drugs and declining performance status in patients with progressing disease are significant
issues in this patient population. Novel approaches with molecularly-targeted agents are
clearly needed.

The combination of vandetanib and fulvestrant addresses the potential to interfere with
multiple interdependent growth-stimulatory pathways simultaneously. Recent work has
revealed cross-talk between epidermal growth factor receptor (EGFR) and estrogen receptor
(ER) pathways. This clinical trial will evaluate the clinical interaction of the EGFR
inhibitor, vandetanib, in combination with the ER down-regulator, fulvestrant.

Inclusion Criteria:

- Pathologically/histologically confirmed non-small cell lung cancer (NSCLC), advanced
(stage IIIB w/ effusion or IV).

- Performance status of 0, 1, or 2

- Brain metastases must be clinically stable after treatment with surgery and/or

- Must have received two prior systemic anti-cancer regimens for recurrent/ metastatic
disease, including one platinum-containing regimen

- Prior radiotherapy, chemotherapy and/or treatment with investigational agents is
allowed provided that the patient has recovered from the treatment-related side
effects to grade ≤1, and that at least 3 weeks has passed since the last dose

- Required laboratory values demonstrating adequate bone marrow, kidney, liver, and
blood clotting function.

- Negative pregnancy test for women of childbearing potential within 7 days prior to
study entry

- Life expectancy of 3 months or more

- Must tolerate intramuscular injections

- No prior or concurrent use of estrogen replacement therapy

- No concurrent use of cytotoxic, immunologic, hormonal, or investigational agent
intended for the antitumor treatment of NSCLC

Exclusion Criteria:

- Prior therapy with any anti-EGFR therapy such as gefitinib (IRESSA), erlotinib
(TARCEVA), vandetanib (ZD6474, ZACTIMA), or fulvestrant (FASLODEX), or an aromatase

- Clinically significant cardiac event such as myocardial infarction, superior vena
cava syndrome, New York Heart Association (NYHA) classification of heart disease ≥ 2
within 3 months before entry

- 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

- Presence of left bundle branch block

- Congenital long QT syndrome, or 1st degree relative with unexplained sudden death
under 40 years of age

- History of QTc prolongation as a result from other medications that required
discontinuation of that medication

- QTc with Bazett's correction that is unmeasurable, or ≥ 480 msec on screening ECG

- Potassium <4.0 mmol/L despite supplementation, or potassium above the CTCAE grade 1
upper limit

- Serum calcium above the CTCAE grade 1 upper limit

- Magnesium below the normal range despite supplementation, or above the CTCAE grade 1
upper limit

- Hypertension not controlled by medical therapy (systolic blood pressure greater than
160 mm Hg or diastolic blood pressure greater than 100 mm Hg)

- Diagnosis of active interstitial lung disease

- Currently active diarrhea that may affect drug absorption

- Previous or current malignancies of other histologies within the last 5 years, with
the exception of cervical carcinoma in situ and basal cell or squamous cell carcinoma
of the skin

- Concomitant use of medications that are potent inducers of CYP3A4 are not allowed
within 2 weeks of study or during the study

- Any unresolved toxicity greater than CTC grade 1 from previous anti-cancer therapy

- Major surgery within 4 weeks, or incompletely healed surgical incision

- Women who are currently pregnant or breast feeding

- History of bleeding diathesis (ie, disseminated intravascular coagulation [DIC],
clotting factor deficiency)

- History of hypersensitivity to active or inactive excipients of fulvestrant (ie
castor oil or Mannitol)

Type of Study:


Study Design:

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

Toleration of combination of fulvestrant/vandetanib

Outcome Time Frame:


Safety Issue:


Principal Investigator

Tien Hoang, M.D.

Investigator Role:

Principal Investigator

Investigator Affiliation:

University of Wisconsin, Madison


United States: Food and Drug Administration

Study ID:




Start Date:

November 2009

Completion Date:

May 2011

Related Keywords:

  • Carcinoma, Non Small Cell Lung
  • non small cell lung cancer
  • vandetanib
  • ZD6474
  • fulvestrant
  • faslodex
  • phase 1
  • Carcinoma
  • Carcinoma, Non-Small-Cell Lung
  • Lung Neoplasms



University of Wisconsin - MadisonMadison, Wisconsin  53792