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Cabozantinib in Advanced Adrenocortical Carcinoma (CaboACC)

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ClinicalTrials.gov Identifier: NCT03612232
Recruitment Status : Recruiting
First Posted : August 2, 2018
Last Update Posted : August 5, 2019
Sponsor:
Information provided by (Responsible Party):
Wuerzburg University Hospital

Tracking Information
First Submitted Date  ICMJE July 12, 2018
First Posted Date  ICMJE August 2, 2018
Last Update Posted Date August 5, 2019
Actual Study Start Date  ICMJE June 4, 2019
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 1, 2018)
progression free survival at 4 months [ Time Frame: 4 months ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT03612232 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 1, 2018)
  • Objective Response Rates (ORR) [ Time Frame: 12 months ]
  • Duration of response (DR) [ Time Frame: 12 months ]
  • progression-free survival [ Time Frame: 12 months ]
  • overall survival [ Time Frame: 12 months ]
  • best percentage change in size of target lesions [ Time Frame: 12 months ]
  • treatment emergent adverse events (CTC-AE 4.03) [ Time Frame: 12 months ]
  • quality of life by EORTC QLQ-C30 [ Time Frame: 12 months ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Cabozantinib in Advanced Adrenocortical Carcinoma
Official Title  ICMJE 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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Adrenocortical Carcinoma
Intervention  ICMJE Drug: Cabozantinib-s-malate
oral cabozantinib-S-malate 60 mg as a daily single oral dose continuously
Study Arms  ICMJE Experimental: Cabozantinib
oral cabozantinib as tablets continuously (60 mg single dose, tablets)
Intervention: Drug: Cabozantinib-s-malate
Publications * Phan LM, Fuentes-Mattei E, Wu W, Velazquez-Torres G, Sircar K, Wood CG, Hai T, Jimenez C, Cote GJ, Ozsari L, Hofmann MC, Zheng S, Verhaak R, Pagliaro L, Cortez MA, Lee MH, Yeung SC, Habra MA. Hepatocyte Growth Factor/cMET Pathway Activation Enhances Cancer Hallmarks in Adrenocortical Carcinoma. Cancer Res. 2015 Oct 1;75(19):4131-42. doi: 10.1158/0008-5472.CAN-14-3707. Epub 2015 Aug 17.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: August 1, 2018)
37
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 2022
Estimated Primary Completion Date December 2021   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Matthias Kroiss, MD, PhD +4993120139740 Kroiss_M@ukw.de
Contact: Martin Fassnacht, MD +49931201-39200 Fassnacht_M@ukw.de
Listed Location Countries  ICMJE Germany
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03612232
Other Study ID Numbers  ICMJE CaboACC
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Product Manufactured in and Exported from the U.S.: Yes
IPD Sharing Statement  ICMJE
Plan to Share IPD: Undecided
Responsible Party Wuerzburg University Hospital
Study Sponsor  ICMJE Wuerzburg University Hospital
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Matthias Kroiss, MD, PhD Wuerzburg University Hospital
PRS Account Wuerzburg University Hospital
Verification Date August 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP