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

NCT01255137 | Completed Phase 2 Results DMC

• 2 other identifiers: 10020310-C-0203
• Study Type: interventional
• Target: 13
• Locations: 1 country
• Sites: 1

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.

Conditions

Adrenal Cortex Neoplasms

Keywords

Selective VEGF Inhibitor; Clinical Activity; Response Rate; Measurable Disease; Biological Markers; Adrenocortical Cancer

Outcome Measures

Primary Outcomes (1)

• 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.

  2 years

Secondary Outcomes (1)

• Number of Participants With Adverse Events

  3/2/11 - 8/2/12

Study Arms (1)

Adrenal Cortex Neoplasms

EXPERIMENTAL

Aggressive cancer that starts in the adrenal gland located at the top of the kidneys.

Drug: Axitinib

Interventions

Axitinib DRUG

5 mg tab orally twice a day with food every 28 days

Also known as: AG-013736

Adrenal Cortex Neoplasms

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Pathologic confirmation of adrenocortical cancer by the Laboratory of Pathology, National Cancer Institute (NCI).
• Measurable disease at presentation.
• A life expectancy of at least 3 months and Eastern Cooperative Oncology Group (ECOG) performance status less than or equal to 2.
• Age greater than or equal to 18 years.
• Last dose of chemotherapy or experimental therapy more than 4 weeks (6 weeks in the case of nitrosourea) prior to enrollment date; 2 weeks if the last therapy was received as part of a phase 0 or exploratory investigational new drug (IND) trial. Last surgery more than 4 weeks prior to enrollment, to allow for wound healing. Core biopsies or fine needle aspiration (FNA) will not require any waiting period.
• Last radiotherapy treatment 4 weeks prior to starting treatment with this protocol and there must be sites of measurable disease that did not receive radiation.
• Prior mitotane therapy is allowed. Patients with a history of a functional tumor who are receiving mitotane to control the excess hormone production may continue to receive mitotane.
• Organ and marrow function as defined below:
• Total bilirubin less than or equal to 1.5 x ULN (upper limit of normal), unless the patient meets the criteria for Gilbert's Syndrome. The upper limit value for bilirubin for subjects with Gilbert's Syndrome is less than 3 mg/dl.
• Note: A diagnosis of Gilbert's disease will be made in the presence of (1) unconjugated hyperbilirubinemia noted on several occasions; (2) normal results from complete blood count (CBC) count, reticulocyte count, and blood smear; (3) normal liver function test results; and (4) an absence of other disease processes that can explain the unconjugated hyperbilirubinemia.
• Aspartate aminotransaminase (AST) less than or equal to 2.5 times ULN, alanine aminotransaminase (ALT) greater than or equal to 2.5 times ULN
• Amylase and lipase equal to, or less than, the institutional ULN.
• Creatinine clearance greater than or equal to 40 ml/min (measured in a timed urine collection) or serum creatinine less than or equal to 1.6 mg/dl
• Absolute neutrophil count greater than or equal to 1000/mm\^3.
• Platelet count greater than or equal to 100,000/ mm\^3.

You may not qualify if:

• Patients with adrenocortical tumors potentially curable by surgical excision alone as determined by the Principal Investigator in discussions with the surgical consultants.
• Patients who have large abdominal masses impinging on bowel or pulmonary masses with encroached vessels and a potential to bleed will be considered on case by case basis after careful consultation with multiple disciplines such as radiologists and surgeons with main intent being patient safety.
• Unstable hypertension defined as a systolic blood pressure greater than 140 mm Hg or diastolic pressure greater than 90 mmHg despite optimal medical management and patients who are receiving more than 1 antihypertensive agent at trial entry, (not including spironolactone) unless the patient has Cushing's Disease with its associated hypertension and is well controlled on medications.
• Untreated brain metastases (or local treatment of brain metastases within the last 6 months) due to the poor prognosis of these patients and difficulty ascertaining the cause of neurologic adverse events.
• Pregnancy, due to the possible adverse effects on the developing fetus.
• Lactating women who are breast-feeding due to the possibility of transmitting axitinib to the child.
• The presence of a second malignancy, other than a skin cancer or in situ cervical cancer because it will complicate the primary objective of the study. Cancer survivors who have been free of disease for at least two years can be enrolled in this study.
• Patients with evidence of a bleeding diathesis.
• Phosphorus level equal to, or less than, the institutional lower limits of normal that cannot be corrected.
• Gastrointestinal abnormalities including:
• inability to take oral medications
• requirement for intravenous alimentation
• prior surgical procedure affecting absorption including total gastric resection
• treatment for active peptic ulcer disease in the past 6 months
• active gastrointestinal bleeding, unrelated to cancer, as evidenced by hematemesis, hematochezia or melena in the past 3 months without evidence of resolution documented by endoscopy or colonoscopy

Sponsors & Collaborators

• National Cancer Institute (NCI): lead
• Pfizer: collaborator

Study Sites (1)

National Institutes of Health Clinical Center, 9000 Rockville Pike

Bethesda, Maryland, 20892, United States

Location

Related Publications (3)

• Plager JE. Carcinoma of the adrenal cortex: clinical description, diagnosis, and treatment. Int Adv Surg Oncol. 1984;7:329-53. No abstract available.

  PMID: 6088397 BACKGROUND

• Luton JP, Cerdas S, Billaud L, Thomas G, Guilhaume B, Bertagna X, Laudat MH, Louvel A, Chapuis Y, Blondeau P, et al. Clinical features of adrenocortical carcinoma, prognostic factors, and the effect of mitotane therapy. N Engl J Med. 1990 Apr 26;322(17):1195-201. doi: 10.1056/NEJM199004263221705.

  PMID: 2325710 BACKGROUND

• Cohn K, Gottesman L, Brennan M. Adrenocortical carcinoma. Surgery. 1986 Dec;100(6):1170-7.

  PMID: 3787475 BACKGROUND

Related Links

• NIH Clinical Center Detailed Web Page

MeSH Terms

Conditions

Adrenal Cortex Neoplasms

Interventions

Axitinib

Condition Hierarchy (Ancestors)

Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Benzamides; Amides; Organic Chemicals; Benzoates; Acids, Carbocyclic; Carboxylic Acids; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Indazoles; Pyrazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Results Point of Contact

• Title: Dr. Tito Fojo
• Organization: National Cancer Institute, National Institutes of Health

FojoT@mail.nih.gov

301-496-2631

Study Officials

• Antonio T Fojo, M.D.

  National Cancer Institute (NCI)

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 4, 2010
• First Posted: December 7, 2010
• Study Start: September 1, 2010
• Primary Completion: December 1, 2012
• Study Completion: December 1, 2012
• Last Updated: June 27, 2013
• Results First Posted: June 27, 2013

Record last verified: 2013-04

Locations

US (1)