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Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

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ClinicalTrials.gov Identifier: NCT01582191
Recruitment Status : Recruiting
First Posted : April 20, 2012
Last Update Posted : August 2, 2019
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Tracking Information
First Submitted Date  ICMJE April 18, 2012
First Posted Date  ICMJE April 20, 2012
Last Update Posted Date August 2, 2019
Actual Study Start Date  ICMJE May 14, 2012
Estimated Primary Completion Date May 31, 2026   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: June 7, 2019)
  • Maximum tolerated dose [ Time Frame: 28 days ]
    Will be defined as the highest dose studied in which the incidence of dose limiting toxicity was less than 33%. Toxicity will be reported by type, frequency, and severity. Worst toxicity grades per patient will be tabulated for selected adverse events and laboratory measurements.
  • Anti-tumor efficacy of the combination in terms of response rate [ Time Frame: Up to 14 years ]
    The response rate will be estimated by dose level and tumor type, along with the exact 95% confidence interval. Efficacy will be evaluated by using the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 criteria described in the supplement for response. Patients with lymphoma will be measured per the World Health Organization (WHO) criteria.
  • Maximum observed serum concentration (Cmax) [ Time Frame: Days 1 and 21 of course 1 and day 1 of course 3 ]
    Will be estimated using standard non-compartmental methods
  • Pharmacodynamic (PD) parameters [ Time Frame: Up to 14 years ]
    PD biomarker concentration will be summarized by time points. The relationship between drug concentrations and PD effects will be explored graphically. Based on review of these graphs, analyses to describe the relationship may also be performed.
  • Observed trough serum concentration (Cmin) [ Time Frame: Days 1 and 21 of course 1 and day 1 of course 3 ]
    Will be estimated using standard non-compartmental methods
  • Area under the serum concentration-time curve (AUC) [ Time Frame: Days 1 and 21 of course 1 and day 1 of course 3 ]
    Will be estimated using standard non-compartmental methods
Original Primary Outcome Measures  ICMJE
 (submitted: April 19, 2012)
Maximum Tolerated Dose (MTD) of Vandetanib with Everolimus [ Time Frame: 28 days ]
Maximum tolerated dose (MTD) defined as highest dose studied in which incidence of dose limiting toxicity (DLT) less than 33%. MTD defined by DLTs that occur in first 28-day cycle (induction phase).
Change History Complete list of historical versions of study NCT01582191 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer
Official Title  ICMJE A Phase 1 Trial of Vandetanib (a Multi-Kinase Inhibitor of EGFR, VEGFR, and RET Inhibitor) in Combination With Everolimus (an mTOR Inhibitor) in Advanced Cancer
Brief Summary This phase I trial studies the side effects and best dose of vandetanib and everolimus when given together in treating patients with cancer that has spread to other places in the body. Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth.
Detailed Description

PRIMARY OBJECTIVES:

I. To determine the maximum tolerated dose (MTD) or highest dose level, and the dose-limiting toxicity (DLT) of vandetanib (a multi-kinase inhibitor of epidermal growth factor receptor [EGFR], vascular endothelial growth factor receptor [VEGFR] and ret proto-oncogene [RET] inhibitor) when used in combination with everolimus (a mammalian target of rapamycin [mTOR] inhibitor) in advanced cancer.

II. Preliminary descriptive assessment of the anti-tumor efficacy of the combination.

III. Preliminary optional assessment of the pharmacokinetic, pharmacodynamic markers of target inhibition and correlates of response.

OUTLINE: This is a dose-escalation study.

Patients receive vandetanib orally (PO) once daily (QD) and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.

After completion of study treatment patients are followed up between 14-28 days at the discretion of the treating physician.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Advanced Malignant Neoplasm
  • Metastatic Malignant Neoplasm
  • Recurrent Malignant Neoplasm
  • Refractory Malignant Neoplasm
Intervention  ICMJE
  • Drug: Everolimus
    Given PO
    Other Names:
    • 42-O-(2-Hydroxy)ethyl Rapamycin
    • Afinitor
    • Certican
    • RAD 001
    • RAD001
    • Votubia
    • Zortress
  • Other: Laboratory Biomarker Analysis
    Optional correlative studies
  • Other: Pharmacological Study
    Optional correlative studies
  • Drug: Vandetanib
    Given PO
    Other Names:
    • AZD6474
    • Caprelsa
    • Zactima
    • ZD-6474
    • ZD6474
Study Arms  ICMJE Experimental: Treatment (vandetanib, everolimus)
Patients receive vandetanib PO QD and everolimus PO QD on days 1-28. Cycles repeat every 28 days in the absence of disease progression or unacceptable toxicity.
Interventions:
  • Drug: Everolimus
  • Other: Laboratory Biomarker Analysis
  • Other: Pharmacological Study
  • Drug: Vandetanib
Publications * Subbiah V, Berry J, Roxas M, Guha-Thakurta N, Subbiah IM, Ali SM, McMahon C, Miller V, Cascone T, Pai S, Tang Z, Heymach JV. Systemic and CNS activity of the RET inhibitor vandetanib combined with the mTOR inhibitor everolimus in KIF5B-RET re-arranged non-small cell lung cancer with brain metastases. Lung Cancer. 2015 Jul;89(1):76-9. doi: 10.1016/j.lungcan.2015.04.004. Epub 2015 Apr 22.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: October 14, 2015)
174
Original Estimated Enrollment  ICMJE
 (submitted: April 19, 2012)
118
Estimated Study Completion Date  ICMJE May 31, 2026
Estimated Primary Completion Date May 31, 2026   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  • Patients with advanced or metastatic cancer that is refractory to standard therapy, relapsed after standard therapy, or who have no standard therapy available that improves survival by at least three months
  • Patients must be at least 3 weeks beyond their previous cytotoxic chemotherapy; patient must be at least 5 half-lives or 3 weeks, whichever is shorter, from their previous targeted or biologic therapy; in addition, patients must be at least 3 weeks beyond the last session of radiation therapy; local palliative radiation therapy that is not delivered to all target lesions is allowed immediately before or during treatment
  • Eastern Cooperative Oncology Group (ECOG) performance status should be less or equal to 3
  • Absolute neutrophil count more or equal to 750/mL
  • Platelets more or equal to 50,000/mL
  • Creatinine less or equal to 3 x upper limit of normal (ULN)
  • Total bilirubin less than or equal to 3.0
  • Women of child-bearing potential and men must agree to use adequate contraception (hormonal or barrier method of birth control; abstinence)

Exclusion Criteria:

  • Uncontrolled intercurrent illness including, but not limited to, uncontrolled infection, uncontrolled asthma, need for hemodialysis, need for ventilatory support
  • Pregnant or lactating women
  • History of hypersensitivity to vandetanib, lactose, murine products, or any component of the formulation
  • History of hypersensitivity to sirolimus, temsirolimus, everolimus
  • History of hypersensitivity to any component of the formulation
  • Patients unwilling or unable to sign informed consent document
  • Presence of cardiac disease that, in the opinion of the investigator, increases the risk of ventricular arrhythmia
  • History (within the last 3 months) or presence of stroke/cerebrovascular accident
  • Congenital long QT syndrome
  • Corrected QT for Fridericia (QTcF) interval greater than 500 ms that is not correctable to less than 500 ms such as with cessation of a causative medication, etc
  • History of myocardial infarction within 6 months with a residual arrhythmia that in the opinion of the investigator, increases the risk of ventricular arrhythmia
  • Presence of a symptomatic bradyarrhythmia or uncompensated heart failure
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE Child, Adult, Older Adult
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Vivek Subbiah, MD 713-563-0393
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT01582191
Other Study ID Numbers  ICMJE 2011-0953
NCI-2012-00782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
0953
2011-0953 ( Other Identifier: M D Anderson Cancer Center )
P30CA016672 ( U.S. NIH Grant/Contract )
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party M.D. Anderson Cancer Center
Study Sponsor  ICMJE M.D. Anderson Cancer Center
Collaborators  ICMJE National Cancer Institute (NCI)
Investigators  ICMJE
Principal Investigator: Vivek Subbiah M.D. Anderson Cancer Center
PRS Account M.D. Anderson Cancer Center
Verification Date July 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP