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.
Recruiting
Phase 1
| Drug | Synonyms | Arms |
|---|---|---|
| Everolimus | 42-O-(2-Hydroxy)ethyl Rapamycin, Afinitor, Certican, RAD 001, RAD001, Votubia, Zortress | Treatment (vandetanib, everolimus) |
| Vandetanib | AZD6474, Caprelsa, Zactima, ZD-6474, ZD6474 | Treatment (vandetanib, everolimus) |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| 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. |
|
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
| Maximum Eligible Age: | N/A |
| Minimum Eligible Age: | N/A |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Maximum tolerated dose |
| Time Frame: | 28 days |
| Safety Issue: | |
| Description: | 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. |
| Phase: | Phase 1 |
| Primary Purpose: | Interventional |
| Overall Status: | Recruiting |
| Lead Sponsor: | M.D. Anderson Cancer Center |
June 18, 2021
