S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors

April 20, 2017 updated by: Southwest Oncology Group

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

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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 Type

Interventional

Phase

  • Phase 1

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 120 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
Pharmacodynamic parameters (percent inhibition of pERK, pKDR, and pEGFR)
Time Frame: 6 months
6 months

Secondary Outcome Measures

Outcome Measure
Time Frame
Correlation of pharmacokinetic profile with pharmacodynamic data and treatment-related toxicities
Time Frame: 6 months
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
Time Frame: 6 months
6 months
Objective tumor response and clinically stable disease in patients with measurable disease at baseline
Time Frame: 6 months
6 months

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Southwest Oncology Group

Collaborators

National Cancer Institute (NCI)

Investigators

  • Study Chair: Monica Mita, MD, Cancer Therapy and Research Center, Texas

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

September 1, 2008

Primary Completion (Anticipated)

September 1, 2009

Study Completion (Anticipated)

September 1, 2009

Study Registration Dates

First Submitted

July 10, 2009

First Submitted That Met QC Criteria

July 10, 2009

First Posted (Estimate)

July 13, 2009

Study Record Updates

Last Update Posted (Actual)

April 24, 2017

Last Update Submitted That Met QC Criteria

April 20, 2017

Last Verified

April 1, 2017

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • S0716
  • SWOG-S0716

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

No

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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