Cabozantinib in Advanced Adrenocortical Carcinoma

• Status: Recruiting
• Trial end date: 2022-06-01
• Target enrollment: 0
• Participant gender: All

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 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Wuerzburg University Hospital

Criteria

Inclusion Criteria:

• histologically confirmed adrenocortical carcinoma that is locally advanced or metastatic who were refractory to or declined standard treatment.

• mitotane administration must have been discontinued 28 days prior to study treatment and a mitotane serum concentration <2 mg/l must be documented.

• measurable disease as defined by the Response Evaluation Criteria in Solid Tumors (RECIST) version 1.1;

• Eastern Cooperative Oncology Group (ECOG) performance status of ≤ 2

• no major bone marrow and organ dysfunction

Exclusion Criteria:

• uncontrolled hypertension

• thromboembolic event 6 months prior to treatment initiation

• tumor manifestation with concern of fistula formation

• QT-interval of > 500 ms in ECG