A Targeted Phase I/II Trial of ZD6474 (Vandetanib; ZACTIMA) Plus the Proteasome Inhibitor, Bortezomib (Velcade ), in Adults With Solid Tumors With a Focus on Hereditary or Sporadic, Locally Advanced or Metastatic Medullary Thyroid Cancer (MTC)

• Status: Terminated
• Trial end date: 2016-12-09

Summary

Background:

• The combination of anti-cancer drugs vandetanib (given orally) and bortezomib (given intravenously) has not been used in humans. However, both drugs have been studied separately. Bortezomib has been approved by the U.S. Food and Drug Administration (FDA) for treating multiple myeloma and mantle cell lymphoma, while vandetanib is still under investigation pending FDA approval.

• Both bortezomib and vandetanib are under investigation for use in treating certain kinds of cancer. Researchers hope that the combination of these two drugs will be more effective than either of them alone.

Objectives:

• To determine if the combination of vandetanib and bortezomib will decrease the amount of the cancer and, if it does, to determine how long the response will last.

• To determine any side effects that may occur with this combination of treatments.

• To determine what doses of each drug are well tolerated and safe when given together.

• To study genetic mutations in tumors to better understand how tumors grow and how these drugs interact with the tumor.

Eligibility:

• Patients 18 years of age and older with solid tumors that cannot be surgically removed and have either recurred or shown further growth. The tumor(s) must be able to be evaluated by X-ray, MRI (magnetic resonance imaging), and CT (computerized tomography) scanning.

• Patients who have been diagnosed with medullary thyroid cancer will participate in Phase II of the study.

Design:

• Tumor samples may be taken at the start of the study for research purposes.

• Phase I: Patient groups will be treated on an outpatient basis with vandetanib and bortezomib, given at increasing doses over four different levels to determine the maximum tolerated dose calculated by height and weight:

• Doses will be given on Days 1, 4, 8, and 11 for each 28-day cycle.

• Two additional levels (Level 1A and Level 1B) may be included in the study, depending on side effects at various levels.

• Phase II: Patients with medullary thyroid cancer will be divided into two groups, with two patients in Group A for every one patient in Group B. No placebo will be involved in this study.

• Group A: Patients will be treated with vandetanib and bortezomib at the maximally tolerated dose of the Phase I study.

• Group B: Patients will be treated with bortezomib alone.

• A second tumor sample may be taken. In patients with thyroid cancer, the second biopsy will be done at the 6-week evaluation (approximately 42 days after beginning). In patients with cancer other than thyroid cancer, the second biopsy will be obtained on Day 4 of either the first or second cycle, after the bortezomib infusion.

• The effects of the drugs will be studied through blood samples and CT scans taken during and after various drug cycles.

• Phase: Phase 1/Phase 2

Details

• Lead Sponsor: National Cancer Institute (NCI)
• Treatments: Bortezomib; Proteasome Inhibitors