Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer
Condition: Adrenal Cortex Neoplasms
MeSH terms: Adrenal Cortex Neoplasms; Adrenocortical Carcinoma
Study type: Interventional
Phase: Phase 2

Summary: 
      Background:

      - 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.

      Objectives:

      - To evaluate the effectiveness of axitinib in individuals who have adrenocortical cancer
      that is inoperable and has not responded to standard treatments.

      Eligibility:

      - Individuals at least 18 years of age who have been diagnosed with adrenocortical cancer
      that has not responded to standard treatments.

      Design:

        -  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.
    

Detailed description: 
      Background:

        -  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.

      Objectives:

        -  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 deoxyribonucleic acid (DNA) examination.

      Eligibility:

        -  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

      Design:

        -  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.
    

Intervention name(s): Axitinib
Intervention type(s): Drug
Intervention description(s): 5 mg tab orally twice a day with food every 28 days
Other intervention name(s): AG-013736
Intervention MeSH terms: Axitinib
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: Selective VEGF Inhibitor; Clinical Activity; Response Rate; Measurable Disease; Biological Markers; Adrenocortical Cancer