Sunitinib in Refractory Adrenocortical Carcinoma

Adrenocortical Carcinoma Clinical Trial

— SIRAC  

Official title:

Sunitinib in Refractory Adrenocortical-Carcinoma Patients Progressing After Cytotoxic Chemotherapy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00453895
• Other study ID #: SIRAC-1
• Status: Completed
• Phase: Phase 2
• Start date: July 2007
• Est. completion date: February 2012

Study information

• Verified date: August 2018
• Source: University of Wuerzburg
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Although a first randomized trial in patients with advanced ACC leading to the establishment of a first line cytotoxic chemotherapy is ongoing (FIRM-ACT), the failure rate even of this FIRM-ACT study is most likely clearly above 50%. Therefore, the majority of participating patients urgently need a new treatment option. However, up to date there is no evidence for a single regimen that might be promising in these treatment-refractory patients with ACC.

Sunitinib is an oral multitargeted tyrosine kinase inhibitor with anti-tumor and antiangiogenic activities, which is successfully tested in the treatment of patients with metastatic renal cell carcinoma, gastrointestinal stromal and neuroendocrine tumors after failure of standard cytotoxic chemotherapy.

The primary objective of this trial is to estimate the response (defined as progression-free survival of ≥ 12 weeks) rate associated with Sunitinib treatment in patients advanced ACC progressing after cytotoxic chemotherapy.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 39
• Est. completion date: February 2012
• Est. primary completion date: August 2011
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histologically confirmed diagnosis of ACC

• Locally advanced or metastatic disease not amenable to radical surgery resection

• Radiologically monitorable disease

• Progressing disease after one to three cytotoxic chemotherapy regimes including a platin-based protocol

• ECOG performance status 0-2

• Life expectancy = 3 months

• Age = 18 years

• Adequate bone marrow reserve (neutrophils = 1500/mm³ and platelets =100.000/mm³) and haemoglobin = 9 g/dl

• Negative pregnancy test and effective contraception in pre-menopausal female and male patients

• Patient´s written informed consent

• Ability to comply with the protocol procedures

• If patients have been participated in another clinical trial evaluating treatment options for ACC (e.g. FIRM-ACT), the patient can only be included in the SIRAC trial, if:

• the patient has discontinued study treatment of the previous trial according to the protocol

• or the study chair of the previous trial gives written approval for inclusion of this individual patient in the SIRAC trial.

Exclusion Criteria:

• History of prior malignancy, except for cured non-melanoma skin cancer, cured in situ cervical carcinoma, or other treated malignancies with no evidence of disease for at least three years.

• Severe renal (serum creatinine > 2.5 x ULN) or hepatic insufficiency (ALT / AST > 2.5 x ULN or ALT/AST >5 x ULN if liver function abnormalities are due to the underlying malignancy and/or total serum bilirubin > 2.0 x ULN) and/or serum albumin < 3g/dl

• Any of the following within the 8 months prior to study drug administration:

myocardial infarction, severe/unstable angina, coronary/peripheral artery bypass graft, symptomatic congestive heart failure, cerebrovascular accident or transient ischemic attack, pulmonary embolism, or other severe thromboembolic event.

• Ongoing cardiac dysrhythmias of NCI CTCAE grade 2, acute atrial fibrillation of any grade, or prolongation of the QTc interval to >470 msec for females

• Left ventricular ejection fraction (LVEF) <45% as measured by echocardiogram

• NCI CTCAE Grade 3 hemorrhage within 4 weeks of starting study treatment

• Hypertension that cannot be controlled by medications (>160/100 mmHg despite optimal medical therapy)

• Pregnancy or breast feeding

• Previous treatment with Sunitinib or any other VEGF- or PDGF-pathway directed agent.

• Current treatment with strong CYP3A4 inhibitors or -inducers

• Current treatment with another investigational drug

• Current treatment with another anti-cancer drug

• Patients with ileus within the last 28 days

• Major surgery, radiation therapy, or systemic therapy within 3 weeks of first study treatment. At least 7 days should elapse from the time of minor surgical procedure including placement of an access device or fine needle aspiration before start of study treatment

• Serious wounds that have not completely healed, active ulcer(s), or significant bone fracture(s).

• Prior radiation therapy to >25% of the bone marrow.

• Cachectic patients with a body mass index < 18 kg/m2

• Any other severe acute or chronic medical or psychiatric condition, or laboratory abnormality that would impart, in the judgment of the investigator, excess risk associated with study participation or study drug administration, or which, in the judgment of the investigator, would make the patient inappropriate for entry into this study.

Related Conditions & MeSH terms

• Adrenocortical Carcinoma
• Carcinoma

Intervention

Drug:
• Sunitinib
50mg Sunitinib

Locations

Country	Name	City	State
Germany	Charite Berlin	Berlin
Germany	Dept. of Medicine I, University of Wuerzburg	Wuerzburg

Sponsors (2)

Lead Sponsor	Collaborator
University of Wuerzburg	Pfizer

Country where clinical trial is conducted

Germany, 

References & Publications (1)

Kroiss M, Quinkler M, Johanssen S, van Erp NP, Lankheet N, Pöllinger A, Laubner K, Strasburger CJ, Hahner S, Müller HH, Allolio B, Fassnacht M. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol M — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of Clinical Benefit Due to Treatment With Sunitinib	Clinical benefit was defined as stable disease or better for at least 12 weeks	12 weeks
Secondary	Assessment of Objective Response Rates	Objective Response Rate defined by RECIST 1.0	12 weeks
Secondary	Assessment of Progression-free Survival	Progression-free survival is defined as time of start of study until documentation of Progress. Progression is defined using Response Evaluation Criteria In Solid Tumors Criteria (RECIST v1.0), as a 20% increase in the sum of the longest diameter of target lesions, or a measurable increase in a non-target lesion, or the appearance of new lesions	up to 400 days
Secondary	Assessment of Overall Survival	Overall Survival was defined as time from start of treatment until death or last follow-up.	up to 36 months
Secondary	Assessment of Toxicity	Adverse events were rated using the National Cancer Institute Common Terminology Criteria for Adverse Events version 3.0 (see http://ctep.cancer.gov/reporting/ctc.html).	up to 400 days

External Links

•   website of the German ACC study group