Clinical trial NCT00937417: S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors
Official title: Phase I Study of the Pharmacokinetics and Pharmacodynamics of ZD6474 in Combination With Docetaxel in Advanced Solid Tumors
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
Conditions: Breast Cancer
Head and Neck Cancer
Lung Cancer
Prostate Cancer
Unspecified Adult Solid Tumor, Protocol Specific
Keywords: unspecified adult solid tumor, protocol specific
recurrent non-small cell lung cancer
stage IV non-small cell lung cancer
stage IV breast cancer
recurrent squamous cell carcinoma of the hypopharynx
stage IV squamous cell carcinoma of the hypopharynx
recurrent squamous cell carcinoma of the larynx
recurrent verrucous carcinoma of the larynx
stage IV squamous cell carcinoma of the larynx
stage IV verrucous carcinoma of the larynx
recurrent adenoid cystic carcinoma of the oral cavity
recurrent mucoepidermoid carcinoma of the oral cavity
recurrent squamous cell carcinoma of the lip and oral cavity
recurrent verrucous carcinoma of the oral cavity
recurrent basal cell carcinoma of the lip
stage IV adenoid cystic carcinoma of the oral cavity
stage IV basal cell carcinoma of the lip
stage IV mucoepidermoid carcinoma of the oral cavity
stage IV squamous cell carcinoma of the lip and oral cavity
stage IV verrucous carcinoma of the oral cavity
recurrent metastatic squamous neck cancer with occult primary
recurrent lymphoepithelioma of the nasopharynx
recurrent squamous cell carcinoma of the nasopharynx
stage IV lymphoepithelioma of the nasopharynx
stage IV squamous cell carcinoma of the nasopharynx
recurrent lymphoepithelioma of the oropharynx
recurrent squamous cell carcinoma of the oropharynx
stage IV lymphoepithelioma of the oropharynx
stage IV squamous cell carcinoma of the oropharynx
recurrent esthesioneuroblastoma of the paranasal sinus and nasal cavity
recurrent inverted papilloma of the paranasal sinus and nasal cavity
recurrent midline lethal granuloma of the paranasal sinus and nasal cavity
recurrent squamous cell carcinoma of the paranasal sinus and nasal cavity
stage IV esthesioneuroblastoma of the paranasal sinus and nasal cavity
stage IV inverted papilloma of the paranasal sinus and nasal cavity
stage IV midline lethal granuloma of the paranasal sinus and nasal cavity
stage IV squamous cell carcinoma of the paranasal sinus and nasal cavity
recurrent salivary gland cancer
stage IV salivary gland cancer
anaplastic thyroid cancer
stage IV follicular thyroid cancer
insular thyroid cancer
stage IV papillary thyroid cancer
recurrent thyroid cancer
thyroid gland medullary carcinoma
recurrent prostate cancer
hormone-resistant prostate cancer
recurrent breast cancer
stage IV prostate cancer
male breast cancer
Lead sponsor: SWOG Cancer Research Network
Sponsor class: NETWORK
Collaborators: name: National Cancer Institute (NCI)
First posted: 2009-07-13
Enrollment: 0
Sex: ALL
Minimum age (years): 18
Maximum age (years): 120
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: Pharmacodynamic parameters (percent inhibition of pERK, pKDR, and pEGFR)
timeFrame: 6 months
Secondary outcomes:
measure: Correlation of pharmacokinetic profile with pharmacodynamic data and treatment-related toxicities
timeFrame: 6 months
measure: Association between scientific correlates (microvessel density, cell death, circulating endothelial cells, ERK and pERK, and serum proteomics) and treatment outcomes and other patient characteristics
timeFrame: 6 months
measure: Objective tumor response and clinically stable disease in patients with measurable disease at baseline
timeFrame: 6 months
Other outcomes:
Locations:
Study officials:
affiliation: Cancer Therapy and Research Center, Texas
name: Monica Mita, MD
role: STUDY_CHAIR
References: