Cabozantinib in Advanced Adrenocortical Carcinoma (NCT03612232) | Clinical Trial Compass
UnknownPhase 2
Cabozantinib in Advanced Adrenocortical Carcinoma
Germany37 participantsStarted 2019-06-04
Plain-language summary
Adrenocortical carcinoma is an orphan malignant disease that has a dismal prognosis in advanced stages. Mitotane is the only approved treatment but is limited by severe toxicity. Efficacy of mitotane is unsatisfactory with an objective response rate of ≈20% in monotherapy in selected patients (Megerle et al., JCEM 2018). Cytotoxic chemotherapy with etoposide, doxorubin and cisplatin (EDP) or streptozotocin (Sz) in addition to mitotane (Fassnacht et al., N Engl J Med 2012) succeeded in a progression-free survival of 5.6 months and 2.2 months, respectively in patients with advanced ACC. Objective response rates were 23 and 9%. EDP plus mitotane is therefore considered as standard treatment of ACC. Results by Phan et al. (Cancer Research 2015) demonstrated expression of c-MET and its ligand HGF in ACC and provide a rationale to therapeutically target c-MET in ACC. In a case series of 16 patients with advanced ACC refractory to mitotane (with the exception of one case) and 3 (median, range 0-8)further lines of therapy, single agent treatment with cabozantinib off label resulted in three partial responses and five additional cases of disease stabilization for four months or longer (Kroiss et al., J Clin Endocrinol Metab 2020).
Who can participate
Age range18 Years
SexALL
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Inclusion criteria
✓. Absolute neutrophil count (ANC) ≥ 1500/μL without colony stimulating factor support, white blood cell count ≥ 2500/μL.
✓. Platelets ≥ 100,000/μL without transfusion
✓. Hemoglobin ≥ 9 g/dL
✓. Bilirubin ≤ 1.5 × the upper limit of normal (ULN). For subjects with known Gilbert's disease, bilirubin ≤ 3.0 mg/dL
✓. Serum albumin ≥ 2.8 g/dl
✓. (PT)/INR or partial thromboplastin time (PTT) test \< 1.3 x the laboratory ULN
✓. Serum creatinine ≤ 2.0 × ULN or creatinine clearance (CrCl) ≥ 30 mL/min. For creatinine clearance estimation, the Cockcroft and Gault equation should be used:
✓. Alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) ≤ 3 x upper limit of normal (ULN). In case of liver metastases ALT and AST ≤ 5.0 x ULN are acceptable. ALP ≤ 5 x ULN with documented bone metastases.
. Prophylactic use of low-dose aspirin for cardio-protection (per local applicable guidelines) and low-dose low molecular weight heparins (LMWH).
✕. Therapeutic doses of LMWH or anticoagulation with direct factor Xa inhibitors rivaroxaban, edoxaban, or apixaban in subjects without known brain metastases who are on a stable dose of the anticoagulant for at least 1 week before first dose of study treatment without clinically significant hemorrhagic complications from the anticoagulation regimen or the tumor.