Sunitinib in Refractory Adrenocortical Carcinoma
Condition: Adrenocortical Carcinoma
MeSH terms: Carcinoma; Adrenocortical Carcinoma
Intervention: Sunitinib
Intervention description: 50mg Sunitinib
Intervention MeSH terms: Sunitinib
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
Intervention model: Single Group Assignment
Masking: None (Open Label)
Enrollment: 39.0
Sex: All
Minimum age: 18 Years
Healthy volunteers: No
Keywords: Adrenal cancer refractory to cytotoxic therapy; Sunitinib; Multitargeted tyrosine-kinase inhibitor

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.