Advanced Malignant Neoplasm, Metastatic Malignant Neoplasm, Recurrent Malignant Neoplasm, Refractory Malignant Neoplasm
Conditions
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.
Interventions
DRUGEverolimus
Given PO
OTHERLaboratory Biomarker Analysis
Optional correlative studies
OTHERPharmacological Study
Optional correlative studies
DRUGVandetanib
Given PO
Sponsors
M.D. Anderson Cancer Center
National Cancer Institute (NCI)
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
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. * 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).
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. * 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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants With Dose Limiting Toxicities (DLT) | First 28-day cycle | 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. |
Countries
United States
Contacts
PRINCIPAL_INVESTIGATORSarina Piha-Paul, MD
M.D. Anderson Cancer Center
Baseline characteristics
| Characteristic | — |
|---|---|
| Age, Categorical <=18 years | 17 Participants |
| Age, Categorical >=65 years | 37 Participants |
| Age, Categorical Between 18 and 65 years | 68 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 2 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 46 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 11 Participants |
| Race (NIH/OMB) White | 98 Participants |
| Region of Enrollment United States | 6 participants |
| Sex: Female, Male Female | 50 Participants |
| Sex: Female, Male Male | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk | EG004 affected / at risk | EG005 affected / at risk |
|---|---|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 5 | 1 / 6 | 1 / 6 | 0 / 6 | 2 / 91 |
| other Total, other adverse events | 7 / 9 | 5 / 5 | 5 / 6 | 5 / 6 | 5 / 6 | 67 / 91 |
| serious Total, serious adverse events | 4 / 9 | 0 / 5 | 4 / 6 | 2 / 6 | 2 / 6 | 39 / 91 |
Outcome results
None listed