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 in (Sz) 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.
There is a need for more effective and less toxic treatments 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 7 patients with advanced ACC refractory to a median of 4 (2-8) prior lines of therapy,
single agent treatment with cabozantinib as an off label therapy resulted in two partial
responses and two additional cases of long-term disease stabilization (Wendler et al, ENDO
2018).
This is a prospective, non-randomized, open-label, single arm, single center phase II study
to investigate the efficacy of oral continuous cabozantinib in adult patients with
histologically confirmed adrenocortical carcinoma that is locally advanced or metastatic and
who were refractory to or declined standard treatment. In patients previously on mitotane,
mitotane administration must have been discontinued 28 days prior to study treatment and a
mitotane serum concentration <2 mg/l has been documented.
Response rate will be calculated as the proportion of patients with progression-free survival
at 4 months.