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

• Status: Withdrawn
• Trial end date: 2011-05-01
• Target enrollment: 0
• Participant gender: All

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.

• Phase: Phase 1
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Wisconsin, Madison
• Collaborators: AstraZeneca; University of Pittsburgh
• Treatments: Estradiol; Fulvestrant

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)