Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer
- 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 vascular endothelial growth factor(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
- Explore the pharmacogenetic analyses of drug metabolism and transport proteins through
germline deoxyribonucleic acid (DNA) examination.
- Adults with pathologic confirmation of ACC by the Laboratory of Pathology, National
Cancer Institute (NCI)
- Diagnosis of recurrent, metastatic, or primary unresectable ACC
- Measurable disease at presentation
- Eastern Cooperative Oncology Group (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 Response Evaluation
Criteria in Solid Tumors (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.
Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Response Rate (RR) of Axitinib Administered Daily, in Patients With Recurrent, Metastatic, or Primary Unresectable Adrenocortical Cancer (ACC)
Response was defined by the Response Evaluation Criteria in Solid Tumors (RECIST). Complete response (CR) is a disappearance of all target lesions. Any pathological lymph nodes (whether target or non-target) must have reduction in short axis to <10mm. Partial response (PR) is at least a 30% decrease in the sum of the diameters of target lesions, taking as reference the baseline sum diameter. Progressive disease (PD) is a 20% increase in the sum of the diameters of target lesions, taking as reference the smallest sum on study (this includes the baseline sum if that is the smallest on study). In addition to the relative increase of 20%, the sum must also demonstrate an absolute increase of at least 5mm (Note: the appearance of one or more new lesions is also considered progression). Stable disease (SD) is neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for PD, taking s reference the smallest sum diameters while on study.
Antonio T Fojo, M.D.
National Cancer Institute (NCI)
United States: Federal Government
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