Phase II Study of PD-1 Inhibitor Combined With Apatinib and Mitotane in the Treatment of Advanced Adrenal Cortical Carcinoma

Summary

Adrenocortical carcinoma (ACC) is a rare aggressive malignant tumor. According to the literature, the 5-year survival rate of ACC is 12%-47%. For patients with advanced ACC, mitotane alone or combined with traditional chemotherapy was the first-line standard treatment, but its progression-free survival was only about 1 year. The efficacy of mitotane monotherapy is approximately 10% to 30%. FIRM-ACT trial reported an objective response rate (ORR) of 23.2% for etoposide, doxorubicin, cisplatin, and mitotane (EDP-M) chemotherapy regimen. Our phase II study found that PD-1 inhibitor camrelizumab and apatinib showed impressive clinical data in the second-line treatment of relapsed and metastatic ACC patients. The aim of this study is to evaluate the efficacy and safety of PD-1 inhibitor camrelizumab combined with apatinib and mitotane in advanced ACC, and to explore a new treatment strategy for patients with advanced ACC.

Timeline

Start

2025-03-15

Primary completion

2026-12-31

Completion

2031-12-31

Publications

• Background Zhu YC, Wei ZG, Wang JJ, Pei YY, Jin J, Li D, Li ZH, Liu ZR, Min Y, Li RD, Yang L, Liu JY, Wei Q, Peng XC. Camrelizumab plus apatinib for previously treated advanced adrenocortical carcinoma: a single-arm phase 2 trial. Nat Commun. 2024 Nov 29;15(1):10371. doi: 10.1038/s41467-024-54661-9.
• Background Habra MA, Stephen B, Campbell M, Hess K, Tapia C, Xu M, Rodon Ahnert J, Jimenez C, Lee JE, Perrier ND, Boraddus RR, Pant S, Subbiah V, Hong DS, Zarifa A, Fu S, Karp DD, Meric-Bernstam F, Naing A. Phase II clinical trial of pembrolizumab efficacy and safety in advanced adrenocortical carcinoma. J Immunother Cancer. 2019 Sep 18;7(1):253. doi: 10.1186/s40425-019-0722-x.
• Background Raj N, Zheng Y, Kelly V, Katz SS, Chou J, Do RKG, Capanu M, Zamarin D, Saltz LB, Ariyan CE, Untch BR, O'Reilly EM, Gopalan A, Berger MF, Olino K, Segal NH, Reidy-Lagunes DL. PD-1 Blockade in Advanced Adrenocortical Carcinoma. J Clin Oncol. 2020 Jan 1;38(1):71-80. doi: 10.1200/JCO.19.01586. Epub 2019 Oct 23.
• Background 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.
• Background Berruti A, Terzolo M, Sperone P, Pia A, Della Casa S, Gross DJ, Carnaghi C, Casali P, Porpiglia F, Mantero F, Reimondo G, Angeli A, Dogliotti L. Etoposide, doxorubicin and cisplatin plus mitotane in the treatment of advanced adrenocortical carcinoma: a large prospective phase II trial. Endocr Relat Cancer. 2005 Sep;12(3):657-66. doi: 10.1677/erc.1.01025.
• Background Tang Y, Liu Z, Zou Z, Liang J, Lu Y, Zhu Y. Benefits of Adjuvant Mitotane after Resection of Adrenocortical Carcinoma: A Systematic Review and Meta-Analysis. Biomed Res Int. 2018 Jun 4;2018:9362108. doi: 10.1155/2018/9362108. eCollection 2018.
• Background Abiven G, Coste J, Groussin L, Anract P, Tissier F, Legmann P, Dousset B, Bertagna X, Bertherat J. Clinical and biological features in the prognosis of adrenocortical cancer: poor outcome of cortisol-secreting tumors in a series of 202 consecutive patients. J Clin Endocrinol Metab. 2006 Jul;91(7):2650-5. doi: 10.1210/jc.2005-2730. Epub 2006 May 2.
• Background Icard P, Goudet P, Charpenay C, Andreassian B, Carnaille B, Chapuis Y, Cougard P, Henry JF, Proye C. Adrenocortical carcinomas: surgical trends and results of a 253-patient series from the French Association of Endocrine Surgeons study group. World J Surg. 2001 Jul;25(7):891-7. doi: 10.1007/s00268-001-0047-y.
• Background Else T, Kim AC, Sabolch A, Raymond VM, Kandathil A, Caoili EM, Jolly S, Miller BS, Giordano TJ, Hammer GD. Adrenocortical carcinoma. Endocr Rev. 2014 Apr;35(2):282-326. doi: 10.1210/er.2013-1029. Epub 2013 Dec 20.
• 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.

Drugs

Indications