S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors

Sponsor

Southwest Oncology Group (Other)

Overall Status

Withdrawn

CT.gov ID

NCT00937417

Collaborator

National Cancer Institute (NCI) (NIH)

Enrollment

Arm

Duration (Months)

Study Details

Study Description

Brief Summary

RATIONALE: Vandetanib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth and by blocking blood flow to the tumor. Drugs used in chemotherapy, such as docetaxel, work in different ways to stop the growth of tumor cells, either by killing the cells or by stopping them from dividing. Giving vandetanib together with docetaxel may kill more tumor cells.

PURPOSE: This phase I trial is studying the side effects and best dose of vandetanib given together with docetaxel in treating patients with advanced solid tumors.

Condition or Disease	Intervention/Treatment	Phase
Breast Cancer Head and Neck Cancer Lung Cancer Prostate Cancer Unspecified Adult Solid Tumor, Protocol Specific	Drug: docetaxel Drug: vandetanib Genetic: proteomic profiling Other: laboratory biomarker analysis Other: pharmacological study	Phase 1

Detailed Description

OBJECTIVES:

Primary

To investigate the differential biological effects in tumor tissues through pharmacodynamic endpoints (percent inhibition of pERK, pKDR, and pEGFR) and their correlation with pharmacokinetics of vandetanib in combination with docetaxel in patients with advanced solid tumors.
To correlate the pharmacodynamic endpoints with the pharmacokinetics of this combination regimen in these patients.
To recommend an optimal biological dose of this combination regimen for further testing.

Secondary

To correlate the pharmacokinetics with safety profiles of two dose levels of vandetanib when given in combination with docetaxel.
To investigate scientific correlates, including serum proteomics and microvessel density (CD31) and cell death (TUNEL) using tumor tissue biopsy samples taken at baseline and during treatment.
To determine the objective response in patients with measurable disease at baseline.

OUTLINE: This is a multicenter study.

Patients receive docetaxel IV over 1 hour on day 1 and oral vandetanib once daily on days 1-21. Courses repeat every 21 days in the absence of disease progression or unacceptable toxicity. After 6 weeks of treatment, patients who experience clinical benefit but poor tolerance to docetaxel may continue treatment with vandetanib alone.

Plasma samples are collected periodically for pharmacokinetic analysis, measurement of vandetanib trough levels, serum biomarker analysis, and serum proteomics. Tumor tissue samples are collected at baseline and once between days 36-38 for pharmacodynamic analysis.

After completion of study treatment, patients are followed up for up to 28 days.

Study Design

Study Type:

Interventional

Actual Enrollment :

0 participants

Allocation:

N/A

Intervention Model:

Single Group Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Phase I Study of the Pharmacokinetics and Pharmacodynamics of ZD6474 in Combination With Docetaxel in Advanced Solid Tumors

Study Start Date :

Sep 1, 2008

Anticipated Primary Completion Date :

Sep 1, 2009

Anticipated Study Completion Date :

Sep 1, 2009

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Arm 1 vandetanib and docetaxel	Drug: docetaxel Drug: vandetanib Genetic: proteomic profiling Other: laboratory biomarker analysis Other: pharmacological study

Arm

Intervention/Treatment

Experimental: Arm 1

vandetanib and docetaxel

Drug: docetaxel

Drug: vandetanib

Genetic: proteomic profiling

Other: laboratory biomarker analysis

Other: pharmacological study

Outcome Measures

Primary Outcome Measures

Pharmacodynamic parameters (percent inhibition of pERK, pKDR, and pEGFR) [6 months]

Secondary Outcome Measures

Correlation of pharmacokinetic profile with pharmacodynamic data and treatment-related toxicities [6 months]
Association between scientific correlates (microvessel density, cell death, circulating endothelial cells, ERK and pERK, and serum proteomics) and treatment outcomes and other patient characteristics [6 months]
Objective tumor response and clinically stable disease in patients with measurable disease at baseline [6 months]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 120 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

DISEASE CHARACTERISTICS:

Histologically or cytologically confirmed advanced solid tumor, including, but not limited to the following:
Non-small cell lung cancer
Metastatic breast cancer
Hormone-refractory prostate cancer
Locally recurrent or metastatic head and neck cancer (including thyroid origin)
Disease for which no standard therapy exists
Tumor amenable to biopsy
Measurable or non-measurable disease
Brain metastases allowed provided patient has undergone brain irradiation (whole brain or gamma knife) AND the metastases have been clinically and radiologically stable for ≥ 6 weeks after completion of irradiation
Patients requiring corticosteroids or anticonvulsants for brain metastases must be on a stable or decreasing dose of corticosteroids and seizure free for ≥ 28 days before study enrollment

PATIENT CHARACTERISTICS:

Zubrod performance status 0-1
ANC ≥ 1,500/mm^3
Platelet count ≥ 100,000/mm^3
SGOT or SGPT ≤ 2.5 times upper limit of normal (ULN)
Bilirubin ≤ 1.5 times ULN
PT/INR ≤ 1.1 times normal
Serum creatinine ≤ 1.8 times ULN OR measured or estimated creatinine clearance > 50 mL/min
Not pregnant or nursing
Negative pregnancy test
Fertile patients must use effective contraception during and for ≥ 3 months after completion of study treatment
Willing to undergo two tumor biopsies and blood and tissue sample submission for correlative laboratory studies
No clinically significant cardiovascular event, including any of the following:
Myocardial infarction or cerebrovascular accident within the past 3 months
Unstable angina pectoris
NYHA class II-IV heart disease within the past 3 months
Symptomatic congestive heart failure
Serious cardiac arrhythmia
No history of cardiac disease that, in the investigator's opinion, increases the risk of ventricular arrhythmia
No history of arrhythmia that is symptomatic or requires treatment (CTCAE grade 3), including any of the following:
Multifocal premature ventricular contractions (PVCs)
Bigeminy or trigeminy
Ventricular tachycardia
Uncontrolled atrial fibrillation
Medically controlled atrial fibrillation allowed
No asymptomatic sustained ventricular tachycardia
No history of or evidence of any of the following on ECG:
History of QTc prolongation as a result from other medication that required discontinuation of that medication
Congenital long QT syndrome
First degree relative with unexplained sudden death under 40 years of age
Presence of left bundle branch block
QTc with Bazett's correction that is unmeasurable or ≥ 480 msec on screening ECG
No uncontrolled hypertension, defined as consistent systolic BP > 160 mm Hg or consistent diastolic BP > 100 mm Hg despite medical management
No intractable nausea or vomiting
No concurrent active diarrhea that may affect the ability to absorb or tolerate vandetanib
No gastrointestinal (GI) tract disease resulting in malabsorption syndrome or a requirement for IV alimentation
No uncontrolled inflammatory GI disease (e.g., Crohn's disease or ulcerative colitis)
No history of allergic reactions attributed to docetaxel or compounds of similar chemical or biological composition to vandetanib, including other quinazoline compounds (e.g., gefitinib or erlotinib)
No history of deep venous thrombosis or pulmonary embolism requiring therapeutic anticoagulation
No known HIV positivity
No other concurrent uncontrolled illness, including, but not limited to the following:
Ongoing or serious active infection
Psychiatric illness or social situation that would limit compliance with study requirements
Prior or concurrent malignancies of other histologies within the past 5 years allowed

PRIOR CONCURRENT THERAPY:

See Disease Characteristics
Recovered from prior therapy (i.e., ≤ grade 2 alopecia and ≤ grade 1 toxicity from all other adverse events)
Prior docetaxel as monotherapy or in combination with other chemotherapeutic agents allowed provided there is potential clinical benefit present, in the investigator's opinion, from the combination of docetaxel and vandetanib
No prior vandetanib
No prior surgical procedures affecting absorption
More than 14 days since prior drugs with a short half-life (e.g., sorafenib or sunitinib) (approval by study coordinator required)
More than 28 days since prior major surgery, chemotherapy, or radiotherapy
More than 28 days since prior investigational agents
More than 2 weeks since prior and no concurrent medications associated with a risk of causing Torsades de Pointes
No concurrent therapeutic anticoagulation (coumadin, warfarin, or low-molecular weight heparin)
Low-dose anticoagulation for indwelling catheter maintenance allowed
No concurrent medication that may cause QTc prolongation
No other concurrent chemotherapy, hormonal therapy, radiotherapy, immunotherapy, or any other type of therapy for the treatment of cancer, except for the following:
Luteinizing hormone-releasing hormone agonists
Bisphosphonates