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
|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|
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 :||Interventional (Clinical Trial)|
|Estimated Enrollment :||174 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|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|
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.
Other: Laboratory Biomarker Analysis
Optional correlative studies
Other: Pharmacological Study
Optional correlative studies
- 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
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
|Contact: Vivek Subbiah, MD||713-563-0393|
|United States, Texas|
|M D Anderson Cancer Center||Recruiting|
|Houston, Texas, United States, 77030|
|Contact: Vivek Subbiah 713-563-0393 email@example.com|
|Principal Investigator: Vivek Subbiah|
|Principal Investigator:||Vivek Subbiah||M.D. Anderson Cancer Center|