Have you or your loved ones been diagnosed with advanced malignant neoplasm?

You may be eligible to participate in a advanced malignant neoplasm clinical trial.

Have you or your loved ones been diagnosed with advanced malignant neoplasm? You may be eligible to participate in a advanced malignant neoplasm clinical trial.

What is a clinical trial? Is participating in a clinical trial right for you? Learn more

Advanced Malignant Neoplasm Clinical Trial in Houston TX

NCT01582191 | Phase 1 | Interventional

Have you or your loved ones been diagnosed with advanced malignant neoplasm?

You may be eligible to participate in a advanced malignant neoplasm clinical trial.

Have you or your loved ones been diagnosed with advanced malignant neoplasm? You may be eligible to participate in a advanced malignant neoplasm clinical trial.

Recruiting

Male & Female

All ages

This study is looking to recruit 174 Participants

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.

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Details for the study

Brief Title

Vandetanib and Everolimus in Treating Patients With Advanced or Metastatic Cancer

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

Brief Summary

This phase I trial studies the side effects and best dose of vandetanib and everolimus when <br /> given together in treating patients with cancer that has spread to other places in the body. <br /> Vandetanib and everolimus may stop the growth of cancer cells by blocking some of the enzymes <br /> 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.

Treatments and/or Procedures

Vandetanib

Given PO

Everolimus

Given PO

Laboratory biomarker analysis

Optional correlative studies

Pharmacological study

Optional correlative studies

Outcome Measures

Outcome measures are the tests that investigators perform to prove whether or not a treatment being tested in a clinical trial is having any effect.

Primary

Maximum tolerated dose

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.

28 days

Primary

Anti-tumor efficacy of the combination in terms of response rate

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.

Up to 14 years

Primary

Pharmacodynamic (PD) parameters

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.

Up to 14 years

Primary

Observed trough serum concentration (Cmin)

Will be estimated using standard non-compartmental methods

Days 1 and 21 of course 1 and day 1 of course 3

Primary

Area under the serum concentration-time curve (AUC)

Will be estimated using standard non-compartmental methods

Days 1 and 21 of course 1 and day 1 of course 3

Primary

Maximum observed serum concentration (Cmax)

Will be estimated using standard non-compartmental methods

Days 1 and 21 of course 1 and day 1 of course 3

Study 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