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

NCT01004419 | Withdrawn Phase 1 DMC

• 2 other identifiers: H-2008-0009CO 07505
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

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.

Conditions

Carcinoma, Non Small Cell Lung

Keywords

non small cell lung cancer; vandetanib; ZD6474; fulvestrant; faslodex; phase 1

Outcome Measures

Primary Outcomes (1)

• Toleration of combination of fulvestrant/vandetanib

  Monthly

Secondary Outcomes (2)

• Response rate to combination of fulvestrant/vandetanib

  End of trial

• Safety of combination of fulvestrant/vandetanib

  Monthly

Study Arms (1)

Vandetanib plus fulvestrant

EXPERIMENTAL

vandetanib by mouth once daily for 28 days plus fulvestrant intra-muscular injection each cycle

Drug: ZD6474 (vandetanib); Drug: Faslodex (Fulvestrant)

Interventions

ZD6474 (vandetanib) DRUG

vandetanib (100 mg or 200 mg or 300 mg) by mouth once daily for 28 days

Also known as: ZD6474, Zactima

Vandetanib plus fulvestrant

Faslodex (Fulvestrant) DRUG

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.

Also known as: Faslodex

Vandetanib plus fulvestrant

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Wisconsin, Madison: lead
• AstraZeneca: collaborator
• University of Pittsburgh: collaborator

MeSH Terms

Conditions

Carcinoma, Non-Small-Cell Lung

Interventions

vandetanib; Fulvestrant

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Neoplasms; Lung Diseases; Respiratory Tract Diseases

Intervention Hierarchy (Ancestors)

Estradiol; Estrenes; Estranes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Estradiol Congeners; Gonadal Steroid Hormones; Gonadal Hormones; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Tien Hoang, M.D.

  University of Wisconsin, Madison

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: October 28, 2009
• First Posted: October 30, 2009
• Study Start: November 1, 2009
• Primary Completion: November 1, 2010
• Study Completion: May 1, 2011
• Last Updated: October 2, 2015

Record last verified: 2015-09