Phase I Trial of Vandetanib (ZD6474, Zactima) and Fulvestrant (Faslodex) as Third-Line Treatment of Advanced Non-Small Cell Lung Cancer
Overview
- Phase
- Phase 1
- Intervention
- ZD6474 (vandetanib)
- Conditions
- Carcinoma, Non Small Cell Lung
- Sponsor
- University of Wisconsin, Madison
- Primary Endpoint
- Toleration of combination of fulvestrant/vandetanib
- Status
- Withdrawn
- Last Updated
- 10 years ago
Overview
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.
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.
Investigators
Eligibility 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
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
Arms & Interventions
Vandetanib plus fulvestrant
vandetanib by mouth once daily for 28 days plus fulvestrant intra-muscular injection each cycle
Intervention: ZD6474 (vandetanib)
Vandetanib plus fulvestrant
vandetanib by mouth once daily for 28 days plus fulvestrant intra-muscular injection each cycle
Intervention: Faslodex (Fulvestrant)
Outcomes
Primary Outcomes
Toleration of combination of fulvestrant/vandetanib
Time Frame: Monthly
Secondary Outcomes
- Response rate to combination of fulvestrant/vandetanib(End of trial)
- Safety of combination of fulvestrant/vandetanib(Monthly)