Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer
- Adrenocortical carcinoma is an aggressive cancer that starts in the adrenal gland at the top of the kidneys. It has a low survival rate if standard treatment options are not effective. Axitinib is an experimental drug that is being studied to determine if it can stop tumors from growing or make them smaller. Researchers are interested in investigating axitinib in individuals with aggressive or otherwise untreatable adrenocortical cancer.
- To evaluate the effectiveness of axitinib in individuals who have adrenocortical cancer that is inoperable and has not responded to standard treatments.
- Individuals at least 18 years of age who have been diagnosed with adrenocortical cancer that has not responded to standard treatments.
- Participants will be screened with a full physical examination and medical history, as well as tumor imaging studies.
- Participants may have a tumor biopsy prior to starting axitinib.
- All participants will receive axitinib to take twice a day with food for 28 days (1 cycle). Participants should not drink grapefruit juice or smoke cigarettes while participating in this study.
- After the first cycle, the dose may be increased and additional cycles will be given if the treatment has not had serious side effects.
- Participants will have regular examinations while taking axitinib, including blood samples and tumor imaging studies to determine if the tumor has stopped growing. Blood pressure levels will be carefully monitored during treatment to evaluate potential risk for high blood pressure.
- Participants may have a second tumor biopsy 20 to 30 days after treatment begins.
- Treatment will continue as directed by the study researchers.
|Study Design:||Allocation: Non-Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer|
- Determine the response rate (RR) of axitinib administered daily, in patients with recurrent, metastatic, or primary unresectable ACC. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- Determine the progression-free survival. To explore the relationship of potential biological markers of axitinib activity with clinical outcomes. [ Time Frame: 3 years ] [ Designated as safety issue: No ]
- To explore the pharmacogenetic analyses of drug metabolism and transport proteins through germline DNA examination.
|Study Start Date:||September 2010|
|Study Completion Date:||December 2012|
|Primary Completion Date:||December 2012 (Final data collection date for primary outcome measure)|
- The response rates of recurrent, metastatic and unresectable adrenocortical cancer (ACC) to mitotane, doxorubicin, etoposide, and cisplatin are low and underscore the need for more effective systemic therapies.
- VEGF expression and evidence of angiogenesis has been found in many ACCs, so it is plausible that interfering with VEGF signaling may result in anti-tumor activity in patients with ACC.
- Axitinib (AG-013736) is an oral, potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptors 1, 2, and 3. Pre-clinical data suggests that the anti-tumor activity of axitinib may result from its anti-angiogenic activity and that this is reversible when treatment is discontinued.
- Given the known clinical safety and efficacy of axitinib, an assessment of its activity in ACC and its impact on the VEGF pathway in ACC could provide valuable information.
- Determine the response rate of axitinib (AG-013736) in recurrent, metastatic, or primary unresectable ACC
- Determine the progression-free survival
- Explore the relationship of potential biological markers of axitinib activity with clinical outcomes.
- Explore the pharmacogenetic analyses of drug metabolism and transport proteins through germline DNA examination.
- Adults with pathologic confirmation of ACC by the Laboratory of Pathology, NCI
- Diagnosis of recurrent, metastatic, or primary unresectable ACC
- Measurable disease at presentation
- ECOG performance status less than or equal to 2
- Patients must not have received prior therapy with a tyrosine kinase (TK) inhibitor
- Phase II, open label, non-randomized trial
- Patients with recurrent, metastatic, or primary unresectable ACC will be given in eight weeks cycles with BID dosing of axitinib (AG-013736).
- Patients will be evaluated for response every eight weeks using RECIST criteria.
- Tumor biopsies are not mandatory but every attempt will be made to obtain these from patients prior to starting axitinib and again 20-30 days after treatment has begun.
- Approximately 40 patients will be needed to achieve the objectives of the trial.
|United States, Maryland|
|National Institutes of Health Clinical Center, 9000 Rockville Pike|
|Bethesda, Maryland, United States, 20892|
|Principal Investigator:||Antonio T Fojo, M.D.||National Cancer Institute (NCI)|