Trial of ZD6474 and Faslodex in Non-Small Cell Lung Cancer
Primary Purpose
Carcinoma, Non Small Cell Lung
Status
Withdrawn
Phase
Phase 1
Locations
Study Type
Interventional
Intervention
ZD6474 (vandetanib)
Faslodex (Fulvestrant)
Sponsored by
About this trial
This is an interventional treatment trial for Carcinoma, Non Small Cell Lung focused on measuring non small cell lung cancer, vandetanib, ZD6474, fulvestrant, faslodex, phase 1
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
- 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)
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
Vandetanib plus fulvestrant
Arm Description
vandetanib by mouth once daily for 28 days plus fulvestrant intra-muscular injection each cycle
Outcomes
Primary Outcome Measures
Toleration of combination of fulvestrant/vandetanib
Secondary Outcome Measures
Response rate to combination of fulvestrant/vandetanib
Safety of combination of fulvestrant/vandetanib
Full Information
NCT ID
NCT01004419
First Posted
October 28, 2009
Last Updated
September 30, 2015
Sponsor
University of Wisconsin, Madison
Collaborators
AstraZeneca, University of Pittsburgh
1. Study Identification
Unique Protocol Identification Number
NCT01004419
Brief Title
Trial of ZD6474 and Faslodex in Non-Small Cell Lung Cancer
Official Title
Phase I Trial of Vandetanib (ZD6474, Zactima) and Fulvestrant (Faslodex) as Third-Line Treatment of Advanced Non-Small Cell Lung Cancer
Study Type
Interventional
2. Study Status
Record Verification Date
September 2015
Overall Recruitment Status
Withdrawn
Why Stopped
Support for investigational products has been withdrawn.
Study Start Date
November 2009 (undefined)
Primary Completion Date
November 2010 (Anticipated)
Study Completion Date
May 2011 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University of Wisconsin, Madison
Collaborators
AstraZeneca, University of Pittsburgh
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Carcinoma, Non Small Cell Lung
Keywords
non small cell lung cancer, vandetanib, ZD6474, fulvestrant, faslodex, phase 1
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
Vandetanib plus fulvestrant
Arm Type
Experimental
Arm Description
vandetanib by mouth once daily for 28 days plus fulvestrant intra-muscular injection each cycle
Intervention Type
Drug
Intervention Name(s)
ZD6474 (vandetanib)
Other Intervention Name(s)
ZD6474, Zactima
Intervention Description
vandetanib (100 mg or 200 mg or 300 mg) by mouth once daily for 28 days
Intervention Type
Drug
Intervention Name(s)
Faslodex (Fulvestrant)
Other Intervention Name(s)
Faslodex
Intervention Description
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.
Primary Outcome Measure Information:
Title
Toleration of combination of fulvestrant/vandetanib
Time Frame
Monthly
Secondary Outcome Measure Information:
Title
Response rate to combination of fulvestrant/vandetanib
Time Frame
End of trial
Title
Safety of combination of fulvestrant/vandetanib
Time Frame
Monthly
10. Eligibility
Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
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)
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Tien Hoang, M.D.
Organizational Affiliation
University of Wisconsin, Madison
Official's Role
Principal Investigator
12. IPD Sharing Statement
Learn more about this trial
Trial of ZD6474 and Faslodex in Non-Small Cell Lung Cancer
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