Adrenocortical Carcinoma
Conditions
Keywords
Adrenal cancer refractory to cytotoxic therapy, Sunitinib, Multitargeted tyrosine-kinase inhibitor
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.
Interventions
DRUGSunitinib
50mg Sunitinib
Sponsors
Pfizer
University of Wuerzburg
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Clinical Benefit Due to Treatment With Sunitinib | 12 weeks | Clinical benefit was defined as stable disease or better for at least 12 weeks |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Objective Response Rates | 12 weeks | Objective Response Rate defined by RECIST 1.0 |
| Assessment of Progression-free Survival | up to 400 days | 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 |
| Assessment of Overall Survival | up to 36 months | Overall Survival was defined as time from start of treatment until death or last follow-up. |
| Assessment of Toxicity | up to 400 days | 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). |
Countries
Germany
Participant flow
Recruitment details
The first patient was included in the study on July 17, 2007, the last patient enrolled on September 18, 2009. The last patient stopped the study drug on November 20, 2009.
Participants by arm
| Arm | Count |
|---|---|
| Sunitinib 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
Sunitinib : | 39 |
| Total | 39 |
Baseline characteristics
| Characteristic | Sunitinib |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 4 Participants |
| Age, Categorical Between 18 and 65 years | 35 Participants |
| Age, Continuous | 51.3 years STANDARD_DEVIATION 12.4 |
| Region of Enrollment Germany | 39 participants |
| Sex: Female, Male Female | 22 Participants |
| Sex: Female, Male Male | 17 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 39 / 39 |
| serious Total, serious adverse events | 10 / 39 |
Outcome results
Primary
Assessment of Clinical Benefit Due to Treatment With Sunitinib
Clinical benefit was defined as stable disease or better for at least 12 weeks
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sunitinib | Assessment of Clinical Benefit Due to Treatment With Sunitinib | 5 Participants |
Secondary
Assessment of Objective Response Rates
Objective Response Rate defined by RECIST 1.0
Time frame: 12 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Sunitinib | Assessment of Objective Response Rates | 0 Participants |
Secondary
Assessment of Overall Survival
Overall Survival was defined as time from start of treatment until death or last follow-up.
Time frame: up to 36 months
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Assessment of Overall Survival | 5.4 monhts |
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
Time frame: up to 400 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Assessment of Progression-free Survival | 83 days |
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).
Time frame: up to 400 days
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Sunitinib | Assessment of Toxicity | 4 number of adverse events/patient |