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

This study has been terminated.
(Support for investigational products has been withdrawn.)
Sponsor:
Collaborators:
AstraZeneca
University of Pittsburgh
Information provided by:
University of Wisconsin, Madison
ClinicalTrials.gov Identifier:
NCT01004419
First received: October 28, 2009
Last updated: March 8, 2010
Last verified: March 2010
  Purpose

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 Intervention Phase
Carcinoma, Non Small Cell Lung
Drug: ZD6474 (vandetanib)
Drug: Faslodex (Fulvestrant)
Phase 1

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: 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

Resource links provided by NLM:


Further study details as provided by University of Wisconsin, Madison:

Primary Outcome Measures:
  • Toleration of combination of fulvestrant/vandetanib [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Response rate to combination of fulvestrant/vandetanib [ Time Frame: End of trial ] [ Designated as safety issue: No ]
  • Safety of combination of fulvestrant/vandetanib [ Time Frame: Monthly ] [ Designated as safety issue: Yes ]

Estimated Enrollment: 24
Study Start Date: November 2009
Estimated Study Completion Date: May 2011
Estimated Primary Completion Date: November 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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)
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01004419

Locations
United States, Wisconsin
University of Wisconsin - Madison
Madison, Wisconsin, United States, 53792
Sponsors and Collaborators
University of Wisconsin, Madison
AstraZeneca
University of Pittsburgh
Investigators
Principal Investigator: Tien Hoang, M.D. University of Wisconsin, Madison
  More Information

No publications provided

Responsible Party: Tien Hoang, M.D., University of Wisconsin - Madison
ClinicalTrials.gov Identifier: NCT01004419     History of Changes
Other Study ID Numbers: H-2008-0009, CO 07505
Study First Received: October 28, 2009
Last Updated: March 8, 2010
Health Authority: United States: Food and Drug Administration

Keywords provided by University of Wisconsin, Madison:
non small cell lung cancer
vandetanib
ZD6474
fulvestrant
faslodex
phase 1

Additional relevant MeSH terms:
Carcinoma, Non-Small-Cell Lung
Lung Neoplasms
Bronchial Neoplasms
Carcinoma, Bronchogenic
Lung Diseases
Neoplasms
Neoplasms by Site
Respiratory Tract Diseases
Respiratory Tract Neoplasms
Thoracic Neoplasms
Estradiol
Fulvestrant
Antineoplastic Agents
Antineoplastic Agents, Hormonal
Estrogen Antagonists
Estrogen Receptor Modulators
Estrogens
Hormone Antagonists
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists
Pharmacologic Actions
Physiological Effects of Drugs
Therapeutic Uses

ClinicalTrials.gov processed this record on October 23, 2014