Unspecified Adult Solid Tumor, Protocol Specific Clinical Trial
Official title:
Phase I Clinical Trial Evaluating the Toxicity, Pharmacokinetics and Biological Effect of Intravenous Bevacizumab (Avastin TM) in Combination With Escalating Doses of Oral AZD2171 for Patients With Advanced Malignancies
This phase I trial is studying the side effects and best dose of bevacizumab and cediranib maleate in treating patients with metastatic or unresectable solid tumor, lymphoma, intracranial glioblastoma, gliosarcoma or anaplastic astrocytoma. Monoclonal antibodies, such as bevacizumab, can block cancer growth in different ways. Some block the ability of cancer cells to grow and spread. Others find cancer cells and help kill them or carry cancer-killing substances to them. Cediranib maleate may stop the growth of cancer cells by blocking some of the enzymes needed for cell growth. Bevacizumab and cediranib maleate may also stop the growth of cancer cells by blocking blood flow to the cancer. Giving bevacizumab together with cediranib maleate may kill more cancer cells.
PRIMARY OBJECTIVES:
I. To evaluate the safety and toxicity profile of intravenous bevacizumab (avastin)
administered in combination with oral AZD2171 (cediranib maleate) for patients with advanced
malignancies.
II. To determine the pharmacokinetic profile of oral AZD2171 in combination with bevacizumab
(avastin) administered to patients with advanced malignancies.
SECONDARY OBJECTIVES:
I. To evaluate the serum concentrations of Nitric Oxide (NO) and Nitric oxide synthase (NOS)
among patients treated with this regimen and to correlate with VEGF expression.
II. To determine changes in the tumor vasculature detected by DCE-MRI among patients treated
with this combination of VEGF receptor blocking agents.
III. To evaluate the potential predictive role of angiogenesis molecular endpoints in
malignant effusion samples.
IV. To assess in a descriptive fashion the efficacy of the studied regimen.
OUTLINE: This is a dose-escalation study.
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral cediranib
maleate once daily on days 1-21. Treatment repeats every 28 days in the absence of disease
progression or unacceptable toxicity.
Cohorts of 3-6 patients receive escalating doses of bevacizumab and cediranib maleate until
the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding
that at which 2 of 3 or 2 of 6 patients experience dose-limiting toxicity.
Blood samples are acquired at baseline, on day 2, and after 2 courses of treatment for
pharmacokinetic studies. Samples are analyzed by TUNEL, immunofluorescence staining,
laser-scanning cytometry, flow cytometry, enzyme-linked immunosorbent assay, and
immunohistochemistry to assess apoptosis in tumor and endothelial cells, microvessel density
mean vessel volume, nitric oxide concentration, and signal transduction pathways (i.e., ERK
½, P38 mitogen-activated protein kinase, protein kinase B, circulating endothelial and
progenitor cells, basic fibroblast growth factor, vascular endothelial growth factor (VEGF)
receptor phosphorylation, VEGF, and hypoxia inducible factor-1α). Some patients also undergo
tissue biopsy at baseline and after 2 courses of treatment for characterization of vascular
and angiogenesis markers. Some patients also undergo DCE-MRI at baseline, once between days
22-24, and after every 2 courses of treatment to assess blood perfusion.
After completion of study treatment, patients are followed for 6 weeks.
;
Endpoint Classification: Safety Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Status | Clinical Trial | Phase | |
---|---|---|---|
Completed |
NCT01828775 -
Palliative Care Intervention in Improving Quality of Life, Psychological Distress, and Communication in Patients With Solid Tumors Receiving Treatment
|
N/A | |
Terminated |
NCT01642342 -
Recombinant Albumin Fusion Protein sEphB4-HSA in Treating Patients With Metastatic or Recurrent Solid Tumors
|
Phase 1 | |
Completed |
NCT00002950 -
Topotecan Plus Sargramostim in Treating Patients With Advanced Cancer
|
Phase 1/Phase 2 | |
Completed |
NCT01705548 -
Hypofractionated Stereotactic Radiosurgery in Treating Patients With Large Brain Metastasis
|
N/A | |
Completed |
NCT02146222 -
VEGFR/PDGFR Dual Kinase Inhibitor X-82 and Docetaxel in Treating Patients With Solid Tumors
|
Phase 1 | |
Terminated |
NCT01602627 -
Hsp90 Inhibitor AUY922 in Treating Older Patients With Advanced Solid Malignancies
|
Phase 1 | |
Completed |
NCT01191216 -
1-Methyl-D-Tryptophan and Docetaxel in Treating Patients With Metastatic Solid Tumors
|
Phase 1 | |
Recruiting |
NCT01137825 -
Registry of Older Patients With Cancer
|
||
Recruiting |
NCT00992303 -
Collecting Tissue Samples From Patients With Cancer Undergoing Radiation Therapy and Healthy Participants
|
||
Completed |
NCT00924651 -
Exercise in Lessening Fatigue Caused by Cancer in Patients Undergoing Chemotherapy
|
Phase 3 | |
Suspended |
NCT00935090 -
3'-Deoxy-3'-[18F] Fluorothymidine PET Imaging in Patients With Cancer
|
N/A | |
Completed |
NCT00949949 -
Everolimus, Gemcitabine Hydrochloride, and Cisplatin in Treating Patients With Unresectable Solid Tumors Refractory to Standard Therapy
|
Phase 1 | |
Withdrawn |
NCT00937417 -
S0716 Vandetanib and Docetaxel in Treating Patients With Advanced Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT00710632 -
Screening to Predict Weight Loss in Patients With Cancer
|
N/A | |
Completed |
NCT00544596 -
R-(-)-Gossypol Acetic Acid, Cisplatin, and Etoposide in Treating Patients With Advanced Solid Tumors or Extensive Stage Small Cell Lung Cancer
|
Phase 1 | |
Completed |
NCT00573690 -
Sorafenib Combined With Cisplatin and Etoposide or Carboplatin and Pemetrexed in Treating Patients With Metastatic Solid Tumors
|
Phase 1 | |
Active, not recruiting |
NCT00436735 -
Nelfinavir in Treating Patients With Metastatic, Refractory, or Recurrent Solid Tumors
|
Phase 1 | |
Completed |
NCT00352443 -
S0528 Lapatinib and Everolimus in Treating Patients With Advanced Solid Tumors or Non-Hodgkin's Lymphoma
|
Phase 1 | |
Completed |
NCT00128622 -
Denileukin Diftitox Followed by Vaccine Therapy in Treating Patients With Metastatic Cancer
|
Phase 1 | |
Completed |
NCT00121277 -
Vorinostat and Capecitabine in Treating Patients With Metastatic or Unresectable Solid Tumors
|
Phase 1 |