The Impact of Mitotane Therapy on Serum Free Proteins in Patients With Adrenocortical Carcinoma

NCT05344027 | Completed FDA Drug

• 1 other identifier: GafREC-Endo202
• Study Type: observational
• Target: 35
• Locations: 1 country
• Sites: 1

Brief Summary

This work will evaluate the effects of mitotane treatment on serum protein concentrations in patients treated for ACC with mitotane therapy and compare them to patients with an adrenal neoplasm and pregnant cohort. All of the individuals were treated at King's Hospital between April 2019 and June 2020. Proteins which will be evaluated during this study, include CBG and TBG.

Conditions

Adrenocortical Carcinoma

Keywords

mitotane; adrenocortical carcinoma; ACC; serum free proteins; cortisol binding globulin; thyroid binding globulin

Outcome Measures

Primary Outcomes (1)

• Examine the effect of mitotane therapy on serum thyroid and cortisol binding proteins in patients with ACC

  The primary objective of this project is to determine the effects of mitotane therapy on serum thyroid binding and cortisol binding protein concentrations in patients with adrenocortical carcinoma and compare concentrations of the same binding proteins in patients with adrenal neoplasms not on treatment with mitotane and to a cohort of pregnant women.

  April 2019-June 2020

Study Arms (3)

ACC on mitotane

Individuals in this group were under care by the Endocrinology Team with a diagnosis of an ACC and on mitotane. These individuals were further divided into 3 groups, depending on whether they had a mitotane plasma concentration, within (14-20mg/L), above or below the therapeutic concentration range.

Drug: Mitotane

Adrenal neoplasm without mitotane

Individuals within this category had an adrenal neoplasm and were not being treated with mitotane therapy.

Pregnant group

Individuals did not have an adrenal neoplasm during this period, nor were they being treated with mitotane. These were healthy pregnant females, who were under the care at KCL during their pregnancy.

Interventions

Mitotane DRUG

Individuals within the intervention group were on mitotane therapy as part of their ACC treatment.

ACC on mitotane

Eligibility Criteria

• Age: 19 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

13 patients with an ACC on mitotane therapy will be investigated. Median age of the ACC and mitotane group: 63.0 (IQR: 46, 72.5) 22% of the studied population were Caucasian white, 14.3% Southeast Asian, 11.4% Black Afro-Caribbean, 2.9% other and 2.9% missing. 6 (46.2%) of the patients with an ACC and on mitotane were male, and 7 (53.8%) were female. 6 (46.2%) individuals with an ACC and on mitotane had a stage of III and 7 (53.8%) had stage IV (according to the AJCC and ENSAT staging system).

You may qualify if:

• Patients included in the analysis were seen in the period between April of 2019 and June 2020 at King's College Hospital NHS Foundation Trust.

You may not qualify if:

• Patients not investigated for a malignant neoplasm/ adrenal neoplasm under the Endocrinology team or were a matched cohort of pregnant women at King's College Hospital NHS Foundation Trust during the period Someone under the age of 18

Sponsors & Collaborators

• King's College Hospital NHS Trust: lead

Study Sites (1)

King's College Hospital NHS Foundation Trust

London, SE5 9RS, United Kingdom

Location

Related Publications (15)

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  PMID: 19473175 BACKGROUND

• Russo M, Scollo C, Pellegriti G, Cotta OR, Squatrito S, Frasca F, Cannavo S, Gullo D. Mitotane treatment in patients with adrenocortical cancer causes central hypothyroidism. Clin Endocrinol (Oxf). 2016 Apr;84(4):614-9. doi: 10.1111/cen.12868. Epub 2015 Aug 18.

  PMID: 26221968 BACKGROUND

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  PMID: 19500769 BACKGROUND

• Allolio B, Fassnacht M. Clinical review: Adrenocortical carcinoma: clinical update. J Clin Endocrinol Metab. 2006 Jun;91(6):2027-37. doi: 10.1210/jc.2005-2639. Epub 2006 Mar 21.

  PMID: 16551738 BACKGROUND

• van Erp NP, Guchelaar HJ, Ploeger BA, Romijn JA, Hartigh Jd, Gelderblom H. Mitotane has a strong and a durable inducing effect on CYP3A4 activity. Eur J Endocrinol. 2011 Apr;164(4):621-6. doi: 10.1530/EJE-10-0956. Epub 2011 Jan 10.

  PMID: 21220434 BACKGROUND

• Fassnacht M, Assie G, Baudin E, Eisenhofer G, de la Fouchardiere C, Haak HR, de Krijger R, Porpiglia F, Terzolo M, Berruti A; ESMO Guidelines Committee. Electronic address: clinicalguidelines@esmo.org. Adrenocortical carcinomas and malignant phaeochromocytomas: ESMO-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2020 Nov;31(11):1476-1490. doi: 10.1016/j.annonc.2020.08.2099. Epub 2020 Aug 27. No abstract available.

  PMID: 32861807 BACKGROUND

• Sada A, Glasgow AE, Lyden ML, Dy BM, Foster TR, Habermann EB, Bancos I, McKenzie TJ. Informing therapeutic lymphadenectomy: Location of regional metastatic lymph nodes in adrenocortical carcinoma. Am J Surg. 2022 Jun;223(6):1042-1045. doi: 10.1016/j.amjsurg.2021.10.014. Epub 2021 Oct 19.

  PMID: 34696848 BACKGROUND

• Lehmann TP, Wrzesinski T, Jagodzinski PP. The effect of mitotane on viability, steroidogenesis and gene expression in NCI-H295R adrenocortical cells. Mol Med Rep. 2013 Mar;7(3):893-900. doi: 10.3892/mmr.2012.1244. Epub 2012 Dec 18.

  PMID: 23254310 BACKGROUND

• Tran TB, Liou D, Menon VG, Nissen NN. Surgical management of advanced adrenocortical carcinoma: a 21-year population-based analysis. Am Surg. 2013 Oct;79(10):1115-8.

  PMID: 24160811 BACKGROUND

• van Seters AP, Moolenaar AJ. Mitotane increases the blood levels of hormone-binding proteins. Acta Endocrinol (Copenh). 1991 May;124(5):526-33. doi: 10.1530/acta.0.1240526.

  PMID: 1903011 BACKGROUND

• Daffara F, De Francia S, Reimondo G, Zaggia B, Aroasio E, Porpiglia F, Volante M, Termine A, Di Carlo F, Dogliotti L, Angeli A, Berruti A, Terzolo M. Prospective evaluation of mitotane toxicity in adrenocortical cancer patients treated adjuvantly. Endocr Relat Cancer. 2008 Dec;15(4):1043-53. doi: 10.1677/ERC-08-0103. Epub 2008 Sep 29.

  PMID: 18824557 RESULT

• Fassnacht M, Dekkers OM, Else T, Baudin E, Berruti A, de Krijger R, Haak HR, Mihai R, Assie G, Terzolo M. European Society of Endocrinology Clinical Practice Guidelines on the management of adrenocortical carcinoma in adults, in collaboration with the European Network for the Study of Adrenal Tumors. Eur J Endocrinol. 2018 Oct 1;179(4):G1-G46. doi: 10.1530/EJE-18-0608.

  PMID: 30299884 RESULT

• Fassnacht M, Terzolo M, Allolio B, Baudin E, Haak H, Berruti A, Welin S, Schade-Brittinger C, Lacroix A, Jarzab B, Sorbye H, Torpy DJ, Stepan V, Schteingart DE, Arlt W, Kroiss M, Leboulleux S, Sperone P, Sundin A, Hermsen I, Hahner S, Willenberg HS, Tabarin A, Quinkler M, de la Fouchardiere C, Schlumberger M, Mantero F, Weismann D, Beuschlein F, Gelderblom H, Wilmink H, Sender M, Edgerly M, Kenn W, Fojo T, Muller HH, Skogseid B; FIRM-ACT Study Group. Combination chemotherapy in advanced adrenocortical carcinoma. N Engl J Med. 2012 Jun 7;366(23):2189-97. doi: 10.1056/NEJMoa1200966. Epub 2012 May 2.

  PMID: 22551107 RESULT

Related Links

• Adrenal Carcinoma Risk Factors
• Lysodren (mitotane) dosing, indications, interactions, adverse effects, and more.
• Drug Metabolism
• Dehydroepiandrosterone and Dehydroepiandrosterone Sulfate - Health Encyclopedia
• Cortisol \| South Tees Hospitals NHS Foundation Trust
• Adrenal Cancer Stages

MeSH Terms

Conditions

Adrenocortical Carcinoma

Interventions

Mitotane

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Adrenal Cortex Neoplasms; Adrenal Gland Neoplasms; Endocrine Gland Neoplasms; Neoplasms by Site; Adrenal Cortex Diseases; Adrenal Gland Diseases; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Hydrocarbons, Chlorinated; Hydrocarbons, Halogenated; Hydrocarbons; Organic Chemicals

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2022
• First Posted: April 25, 2022
• Study Start: April 11, 2022
• Primary Completion: January 30, 2023
• Study Completion: March 1, 2023
• Last Updated: March 8, 2023

Record last verified: 2023-03

Locations

GB (1)