Phase II Study of Axitinib (AG-013736) With Evaluation of the VEGF-Pathway in Metastatic, Recurrent or Primary Unresectable Adrenocortical Cancer

Phase 2

Completed

Conditions: Adrenal Cortex Neoplasms

Interventions: Drug: Axitinib

Registration Number: NCT01255137

Lead Sponsor: National Cancer Institute (NCI)

Brief 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.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 13

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Adrenal Cortex Neoplasms	Axitinib	Aggressive cancer that starts in the adrenal gland located at the top of the kidneys.

Primary Outcome Measures

Name	Time	Method
Response Rate (RR) of Axitinib Administered Daily, in Patients With Recurrent, Metastatic, or Primary Unresectable Adrenocortical Cancer (ACC)	2 years	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.

Secondary Outcome Measures

Name	Time	Method
Number of Participants With Adverse Events	3/2/11 - 8/2/12	Here is the number of participants with adverse events. For a detailed list of adverse events, see the adverse events module.