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Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT01582191
Recruitment Status : Recruiting
First Posted : April 20, 2012
Last Update Posted : December 12, 2022
Sponsor:
Collaborator:
National Cancer Institute (NCI)
Information provided by (Responsible Party):
M.D. Anderson Cancer Center

Study Description
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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.

Condition or disease Intervention/treatment Phase
Advanced Malignant Neoplasm Metastatic Malignant Neoplasm Recurrent Malignant Neoplasm Refractory Malignant Neoplasm Drug: Everolimus Other: Laboratory Biomarker Analysis Other: Pharmacological Study Drug: Vandetanib Phase 1

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 Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 174 participants
Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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
Actual Study Start Date : May 14, 2012
Estimated Primary Completion Date : May 31, 2026
Estimated Study Completion Date : May 31, 2026

Resource links provided by the National Library of Medicine


Arms and Interventions
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Arm Intervention/treatment
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.
 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


Outcome Measures
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Primary Outcome Measures :
  1. 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.

  2. 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.

  3. 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

  4. 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.

  5. 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

  6. 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


Eligibility Criteria
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Ages Eligible for Study:   Child, Adult, Older Adult
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01582191


Contacts
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Contact: Vivek Subbiah, MD 713-563-0393

Locations
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United States, Texas
M D Anderson Cancer Center Recruiting
Houston, Texas, United States, 77030
Contact: Vivek Subbiah    713-563-0393    vsubbiah@mdanderson.org   
Principal Investigator: Vivek Subbiah         
Sponsors and Collaborators
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Investigators
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Principal Investigator: Vivek Subbiah M.D. Anderson Cancer Center
More Information
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Additional Information:

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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Responsible Party: M.D. Anderson Cancer Center
ClinicalTrials.gov Identifier: NCT01582191    
Other Study ID Numbers: 2011-0953
NCI-2012-00782 ( Registry Identifier: CTRP (Clinical Trial Reporting Program) )
0953
2011-0953 ( Other Identifier: M D Anderson Cancer Center )
First Posted: April 20, 2012    Key Record Dates
Last Update Posted: December 12, 2022
Last Verified: December 2022
Additional relevant MeSH terms:
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Neoplasms
Recurrence
Disease Attributes
Pathologic Processes
Everolimus
MTOR Inhibitors
Protein Kinase Inhibitors
 Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents