Brief Title
Cabozantinib in Advanced Adrenocortical Carcinoma
Official Title
Phase II Study to Evaluate the Effects of Cabozantinib in Patients With Unresectable/Metastatic Adrenocortical Carcinoma
Brief 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.
Study Phase
Phase 2
Study Type
Interventional
Primary Outcome
progression free survival at 4 months
Secondary Outcome
Objective Response Rates (ORR)
Condition
Adrenocortical Carcinoma
Intervention
Cabozantinib-s-malate
Study Arms / Comparison Groups
Cabozantinib
Description: oral cabozantinib as tablets continuously (60 mg single dose, tablets)
Publications
* Includes publications given by the data provider as well as publications identified by National Clinical Trials Identifier (NCT ID) in Medline.
Recruitment Information
Recruitment Status
Drug
Estimated Enrollment
37
Start Date
June 4, 2019
Completion Date
June 2022
Primary Completion Date
December 2021
Eligibility 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
Gender
All
Ages
18 Years - N/A
Accepts Healthy Volunteers
No
Contacts
Matthias Kroiss, MD, PhD, +4993120139740, [email protected]
Location Countries
Germany
Location Countries
Germany
Administrative Informations
NCT ID
NCT03612232
Organization ID
CaboACC
Responsible Party
Sponsor
Study Sponsor
Wuerzburg University Hospital
Study Sponsor
Matthias Kroiss, MD, PhD, Principal Investigator, Wuerzburg University Hospital
Verification Date
August 2019