Clinical trial NCT00453895: Sunitinib in Refractory Adrenocortical Carcinoma
Official title: Sunitinib in Refractory Adrenocortical-Carcinoma Patients Progressing After Cytotoxic Chemotherapy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Adrenocortical Carcinoma
Keywords: Adrenal cancer refractory to cytotoxic therapy
Sunitinib
Multitargeted tyrosine-kinase inhibitor
Lead sponsor: University of Wuerzburg
Sponsor class: OTHER
Collaborators: name: Pfizer
First posted: 2007-03-29
Enrollment: 39
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

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.


Eligibility criteria: 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.

Primary outcomes:
measure: Assessment of Clinical Benefit Due to Treatment With Sunitinib
timeFrame: 12 weeks
Secondary outcomes:
measure: Assessment of Objective Response Rates
timeFrame: 12 weeks
measure: Assessment of Progression-free Survival
timeFrame: up to 400 days
measure: Assessment of Overall Survival
timeFrame: up to 36 months
measure: Assessment of Toxicity
timeFrame: up to 400 days
Other outcomes:
Locations:
city: Berlin
country: Germany
facility: Charite Berlin
city: Wuerzburg
country: Germany
facility: Dept. of Medicine I, University of Wuerzburg
Study officials:
affiliation: University of Wuerzburg
name: Martin Fassnacht, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.