A Targeted Phase I/II Trial of ZD6474 (Vandetanib; ZACTIMA) Plus the Proteasome Inhibitor, Bortez… (NCT00923247) | Clinical Trial Compass
TerminatedPhase 1/2
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)
Stopped: Terminated due to slow accrual,primary endpoint reached \& investigator left NIH.
United States22 participantsStarted 2009-02-19
Plain-language 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.
Who can participate
Age range18 Years – 80 Years
SexALL
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Inclusion criteria
✓. Pathologic confirmation of cancer by the Laboratory of Pathology, National Cancer Institute (NCI)
✓. Phase I: Diagnosis of recurrent, metastatic or primary unresectable solid tumor that does not have curative standard treatment.
✓. Measurable disease at presentation: Either by Response Evaluation Criteria in Solid Tumors (RECIST) or by measurement of serum markers (calcitonin, carcinoembryonic antigen (CEA), prostate specific antigen (PSA) or cancer antigen 125 or carbohydrate antigen 125 (CA-125) in the dose-finding portion of the study; with disease measurable by RECIST required only in the phase II cohort.
✓. A life expectancy of at least 3 months and Eastern Cooperative Oncology Group (ECOG) performance status 0 1.
✓. Age greater than or equal to 18 years
✓. Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date; unless the last therapy consisted of an oral agent whose average half life is known to be less than 48 hours in which case only 2 weeks need to have elapsed. Regardless of the therapy, any toxicity greater than Common Terminology Criteria in Adverse Events (CTCAE) grade 1 from previous anti-cancer therapy must have been resolved.
✓. Last radiotherapy treatment 4 weeks prior to starting treatment with this protocol with the exception of palliative radiotherapy and there must be sites of measurable disease that did not receive radiation.
What they're measuring
1
Phase I: Maximum Tolerated Dose (MTD) of Daily Oral Vandetanib
Timeframe: 80 days
2
Phase I: Maximum Tolerated Dose (MTD) of Daily Oral Bortezomib
Timeframe: 80 days
3
Phase 2: Tumor Response in Adults With a Diagnosis of Medullary Thyroid Cancer (MTC) Treated With Daily Oral Vandetanib and Bortezomib
Timeframe: 4 months
4
Phase 2: Progression Free Survival in Adults With a Diagnosis of Medullary Thyroid Cancer (MTC) Treated With Daily Oral Vandetanib and Bortezomib
✕. Patients with cancer potentially curable by surgical excision alone or patients who have not received therapy that might be considered standard and potentially curable.
✕. Evidence of severe or uncontrolled systemic disease or any concurrent condition including, but not limited to symptomatic congestive heart failure, unstable angina pectoris, unstable hypertension, seizure disorder, or psychiatric illness which in the Investigators opinion makes it undesirable for the patient to participate in the trial or which would jeopardize compliance with the protocol.
✕. Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic toxicities.
✕. During Phase II enrollment: Prior therapy with vandetanib.
✕. Women who are currently pregnant or breast-feeding, due to the possible adverse effects on the developing fetus and infants.
✕. The presence of a second malignancy within the last 2 years, other than squamous cell carcinoma of the skin or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least two years can be enrolled in this study.
✕. Patients with evidence of a bleeding diathesis that cannot be corrected with standard therapy or factor replacement.
✕. Any unresolved toxicity greater than CTCAE grade 1 (except alopecia) from previous anticancer therapy. Patients with grade 1 neuropathy will be evaluated on a case by case basis for entry into study. Baseline conditions will be taken into consideration.