Advanced Malignant NeoplasmPhase 1NCT01582191
Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer
A Phase 1 study testing Everolimus, Laboratory Biomarker Analysis and Pharmacological Study in people with Advanced Malignant Neoplasm and Metastatic Malignant Neoplasm, run by M.D. Anderson Cancer Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm
- What is being tested?
- Everolimus, Laboratory Biomarker Analysis and Pharmacological Study
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 123 participants
- Where
- 1 siteUnited States
- Study dates
- 14 May 2012to 22 Oct 2025
- Phase
- Phase 1
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 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.
- ECOG performance status should be less or equal to 3
- Patients must have organ and marrow function defined as: Absolute neutrophil count more or equal to 750/mL; platelets more or equal to 50,000/mL; creatinine less or equal to 3x 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).
Who cannot join
- 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.
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- 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.
- QTcF interval greater than 500 ms that is not correctable to less than 500ms 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 bradyarrhthmia or uncompensated heart failure.
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the detailed description
PRIMARY OBJECTIVES:
- 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.
- Conditions
- Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm, Refractory Malignant Neoplasm
- Being tested
- Everolimus, Laboratory Biomarker Analysis, Pharmacological Study, Vandetanib
- Medical subject headings
- Neoplasm Metastasis, Recurrence, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
EverolimusDrug
Also called 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001
Given PO
Laboratory Biomarker AnalysisOther
Optional correlative studies
Optional correlative studies
VandetanibDrug
Also called AZD6474, Caprelsa, Zactima, ZD-6474
Given PO
| Study group | Role | What they receive |
|---|---|---|
| Treatment (vandetanib, everolimus) | Experimental | 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. Receives: Drug: Everolimus; Other: Laboratory Biomarker Analysis; Other: Pharmacological Study; Drug: Vandetanib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With Dose Limiting Toxicities (DLT)
DLT is defined as any clinically significant grade 3 or 4 non-hematologic toxicity as defined in the NCI-CTCAE v3.0, expected and believed to be related to the study medications, any Grade 4 hematologic toxicity lasting 2 weeks or longer (as defined by NCI-CTCAE) or associated with bleeding and/or sepsis; Grade 3 to 4 thrombocytopenia lasting 7 days or thrombocytopenia associated with active bleeding or requiring platelet transfusion; Grade 3 nausea/vomiting lasting > 48 hours or any Grade 4 nausea/vomiting despite maximum anti-nausea regimens (i.e. excluding Grade 3 nausea or Grade 3 to 4 vomiting or diarrhea in patients who had not received optimal antiemetic and anti-diarrheal treatment); and any other clinically significant Grade 3 non-hematologic toxicity including symptoms or signs of vascular leak or cytokine release syndrome; or any severe or life-threatening complications or abnormality not defined in the NCI-CTCAE that is attributable to the therapy.
Measured: First 28-day cycle
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Apr 2012 (estimated)
- Study start14 May 2012
- Primary completion22 Oct 2025
- Study completion22 Oct 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Advanced Malignant NeoplasmStudies of the same condition, open and under way.
- More trials run by M.D. Anderson Cancer CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 123 participants (actual)
Sponsor and investigators
- Lead sponsor
- M.D. Anderson Cancer Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Cancer Institute (NCI)
- Responsible party
- Sponsor
- Investigators
- Sarina Piha-Paul, MD, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01582191
- Sponsor's protocol ID
- 2011-0953
- Other IDs
- NCI-2012-00782, 0953, 2011-0953
- Status last verified
- Aug 2026
- First submitted
- 18 Apr 2012
- Last updated
- 28 Aug 2026
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
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.
PubMed 25982012