Sunitinib in Refractory Adrenocortical Carcinoma

NCT00453895 | Completed Phase 2 Results

• 1 other identifier: SIRAC-1
• Study Type: interventional
• Target: 39
• Locations: 1 country
• Sites: 2

Brief 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.

Conditions

Adrenocortical Carcinoma

Keywords

Adrenal cancer refractory to cytotoxic therapy; Sunitinib; Multitargeted tyrosine-kinase inhibitor

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (4)

• Assessment of Objective Response Rates

  12 weeks

• Assessment of Progression-free Survival

  up to 400 days

• Assessment of Overall Survival

  up to 36 months

• Assessment of Toxicity

  up to 400 days

Study Arms (1)

Sunitinib

EXPERIMENTAL

Sunitinib will be administered 50 mg per day for 4 weeks followed by 2 weeks off. treatment will continue until progressive disease or unacceptable toxicity

Drug: Sunitinib

Interventions

Sunitinib DRUG

50mg Sunitinib

Sunitinib

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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).

Sponsors & Collaborators

• University of Wuerzburg: lead
• Pfizer: collaborator

Study Sites (2)

Charite Berlin

Berlin, Germany

Location

Dept. of Medicine I, University of Wuerzburg

Würzburg, 97080, Germany

Location

Related Publications (1)

• Kroiss M, Quinkler M, Johanssen S, van Erp NP, Lankheet N, Pollinger A, Laubner K, Strasburger CJ, Hahner S, Muller HH, Allolio B, Fassnacht M. Sunitinib in refractory adrenocortical carcinoma: a phase II, single-arm, open-label trial. J Clin Endocrinol Metab. 2012 Oct;97(10):3495-503. doi: 10.1210/jc.2012-1419. Epub 2012 Jul 26.

  PMID: 22837187 RESULT

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Sunitinib

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Pyrroles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring

Limitations and Caveats

A limitation arises from the fact that imaging prior study entry was not standardized. Therefore we cannot provide data regarding the dynamics of tumor growth before initiation of sunitinib.

Results Point of Contact

• Title: Prof. Dr. Martin Fassnacht
• Organization: University of Würzburg

fassnacht_m@medizin.uni-wuerzburg.de

+49-931-201-39201

Study Officials

• Martin Fassnacht, MD

  University of Wuerzburg

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor for Medicine and Endocrinology

Study Record Dates

• First Submitted: March 28, 2007
• First Posted: March 29, 2007
• Study Start: July 1, 2007
• Primary Completion: August 1, 2011
• Study Completion: February 1, 2012
• Last Updated: January 31, 2019
• Results First Posted: January 31, 2019

Record last verified: 2018-08

Locations

DE (2)