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Trial of ZD6474 and Faslodex in Non-Small Cell Lung Cancer

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: NCT01004419
Recruitment Status : Withdrawn (Support for investigational products has been withdrawn.)
First Posted : October 30, 2009
Last Update Posted : October 2, 2015
University of Pittsburgh
Information provided by (Responsible Party):
University of Wisconsin, Madison

Brief Summary:
The purpose of this study is to evaluate the safety and tolerability of vandetanib and fulvestrant; to find the maximum tolerated dose of these two drugs; and to evaluate response rate and assess toxicity of this combination.

Condition or disease Intervention/treatment Phase
Carcinoma, Non Small Cell Lung Drug: ZD6474 (vandetanib) Drug: Faslodex (Fulvestrant) Phase 1

Detailed Description:

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.

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Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 0 participants
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: Phase I Trial of Vandetanib (ZD6474, Zactima) and Fulvestrant (Faslodex) as Third-Line Treatment of Advanced Non-Small Cell Lung Cancer
Study Start Date : November 2009
Estimated Primary Completion Date : November 2010
Estimated Study Completion Date : May 2011

Resource links provided by the National Library of Medicine

Arm Intervention/treatment
Experimental: Vandetanib plus fulvestrant
vandetanib by mouth once daily for 28 days plus fulvestrant intra-muscular injection each cycle
Drug: ZD6474 (vandetanib)
vandetanib (100 mg or 200 mg or 300 mg) by mouth once daily for 28 days
Other Name: ZD6474, Zactima

Drug: Faslodex (Fulvestrant)
Fulvestrant 500 mg intra-muscular injection on Day 1 and 250 mg Day 15 of cycle 1 Cycles 2 and beyond: Fulvestrant 500 mg intra-muscular injection on Day 1, every 28 days.
Other Name: Faslodex

Primary Outcome Measures :
  1. Toleration of combination of fulvestrant/vandetanib [ Time Frame: Monthly ]

Secondary Outcome Measures :
  1. Response rate to combination of fulvestrant/vandetanib [ Time Frame: End of trial ]
  2. Safety of combination of fulvestrant/vandetanib [ Time Frame: Monthly ]

Information from the National Library of Medicine

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

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 radiotherapy
  • 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 inhibitor
  • 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)

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): NCT01004419

Sponsors and Collaborators
University of Wisconsin, Madison
University of Pittsburgh
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Principal Investigator: Tien Hoang, M.D. University of Wisconsin, Madison

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Responsible Party: University of Wisconsin, Madison Identifier: NCT01004419    
Other Study ID Numbers: H-2008-0009
CO 07505
First Posted: October 30, 2009    Key Record Dates
Last Update Posted: October 2, 2015
Last Verified: September 2015
Keywords provided by University of Wisconsin, Madison:
non small cell lung cancer
phase 1
Additional relevant MeSH terms:
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Lung Neoplasms
Carcinoma, Non-Small-Cell Lung
Respiratory Tract Neoplasms
Thoracic Neoplasms
Neoplasms by Site
Lung Diseases
Respiratory Tract Diseases
Carcinoma, Bronchogenic
Bronchial Neoplasms
Antineoplastic Agents, Hormonal
Antineoplastic Agents
Estrogen Receptor Antagonists
Estrogen Antagonists
Hormone Antagonists
Hormones, Hormone Substitutes, and Hormone Antagonists
Physiological Effects of Drugs