PFS and OS of Patients With Advanced Neuroendocrine Cancer (NEN) After Systemic Treatment

Neuroendocrine Tumors Clinical Trial

Official title:

Outcomes of Patients With Advanced Neuroendocrine Cancer (NEN) Treated With Systemic Treatment: Somatostatin Analogues, Molecular Targeted Therapy, Chemotherapy and Peptide Radioisotope Therapy - a Retrospective Analysis.

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04331912
• Other study ID #: NEN_2019
• Status: Recruiting
• Start date: July 1, 2019
• Est. completion date: December 31, 2023

Study information

• Verified date: May 2021
• Source: University of Warmia and Mazury
• Contact: Jaroslaw B Cwikla, MD, PhD
• Phone: +48 602112599
• Email: jbcwikla[@]interia.pl
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

This is a retrospective study. The analysis includes patients with advanced neuroendocrine cancer (NEN) treated with systemic therapy, because of inoperable primary tumor or/and metastasis, clinical, imaging, biochemical disease progression and no standard method of treatment hormone overproduction symptoms. The data of patients with advanced NEN with histopathological confirmation is collected from medical records. The progression-free survival (PFS), overall survival (OS) and influence of various factors on survival will be estimated. The research will be conducted for above 3 years on planned group 1500 patients. The aim of the study is to estimate median OS and PFS in advanced NEN patients treated with different schedule of systemic treatment.

Description:

This is a retrospective study. The analysis includes patients with advanced neuroendocrine cancer (NEN) treated with systemic therapy, because of inoperable primary tumor or/and metastasis, clinical, imaging, biochemical disease progression and no standard method of treatment hormone overproduction symptoms. Systemic treatment including: somatostatin receptor analogues, molecular targeted therapy (sunitinib and everolimus), chemotherapy and peptide radioisotope therapy (Peptide Receptor Radionuclide Therapy). The data of patients with advanced NEN with histopathological or/and clinical or/and biochemical confirmation is collected from medical records. Neuroendocrine cancer from digestive system, respiratory system and another rarely occurring cancer including cancer connected with genetic syndromes like: MEN1, MEN2, VHL, NF1, SDHx will be included. The progression-free survival (PFS), overall survival (OS) and influence of various factors on survival will be estimated. Analyzed factors: age, sex, ethnicity, specific symptoms at the time of diagnosis, carcinoid heart disease, level of 5HIAA in DZM, level of CgA, liver test, size of tumor, cell differentiation of tumor based on Ki-67 index, liver metastases. The research will be conducted for above 3 years since July 2019 till December 2022 on planned group 1500 patients. The aim of the study is to estimate median OS and PFS in advanced NEN patients treated with different schedule of systemic treatment. The second goal is to create clinical practice recommendation based on potential prognostic factors of OS and PFS due to type of therapy in different NEN subgroups.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 100
• Est. completion date: December 31, 2023
• Est. primary completion date: December 31, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 87 Years

Eligibility

Inclusion Criteria:

• Adults =18 years old, male or female,
• Patients with histopathological confirmation of advanced neuroendocrine cancer (NEN),
• Patients with NETG1, NETG2 based on Ki-67,
• Patients with diagnosed NEN, who did not receive prior treatment and were qualified to systemic treatment,
• Patients with advanced NEN who previously received first-line systemic therapy or second-line systemic therapy,
• Patients with advanced, inoperable NEN cancer before the treatment, during the treatment and after the treatment regardless of lines of systemic therapy,
• Patients with diagnosed NEN and performance status (PS) =3 according to ECOG/WHO classification, who received systemic therapy.

Exclusion Criteria:

• Patients without histopathological confirmation of neuroendocrine carcinoma (NEN),
• Patients with diagnosed another type of cancer or benign tumor confirmed in histopathological examination,
• Patients treated prior with intention to treat (ITT),
• Patients with residual disease in further clinical follow-up without active systemic treatment,
• Patients with advanced, progressive and poor performance status, who were disqualified from further systemic treatment,
• Patients, who finished treatment during first month or their further disease process was unknown.

Related Conditions & MeSH terms

• Carcinoma, Neuroendocrine
• Neuroendocrine Tumors

Locations

Country	Name	City	State
Poland	University of Warmia and Mazury in Olsztyn	Olsztyn	Warminsko-Mazurskie
Poland	Diagnostic and Therapy Center - Gammed	Warsaw

Sponsors (1)

Lead Sponsor	Collaborator
University of Warmia and Mazury

Country where clinical trial is conducted

Poland, 

References & Publications (20)

Delle Fave G, O'Toole D, Sundin A, Taal B, Ferolla P, Ramage JK, Ferone D, Ito T, Weber W, Zheng-Pei Z, De Herder WW, Pascher A, Ruszniewski P; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Gastroduodenal Neuroendocrine N — View Citation

Falconi M, Eriksson B, Kaltsas G, Bartsch DK, Capdevila J, Caplin M, Kos-Kudla B, Kwekkeboom D, Rindi G, Klöppel G, Reed N, Kianmanesh R, Jensen RT; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for the Management of Patients — View Citation

Garcia-Carbonero R, Sorbye H, Baudin E, Raymond E, Wiedenmann B, Niederle B, Sedlackova E, Toumpanakis C, Anlauf M, Cwikla JB, Caplin M, O'Toole D, Perren A; Vienna Consensus Conference participants. ENETS Consensus Guidelines for High-Grade Gastroenterop — View Citation

Greene FL. TNM staging for malignancies of the digestive tract: 2003 changes and beyond. Semin Surg Oncol. 2003;21(1):23-9. Review. — View Citation

Iasonos A, Schrag D, Raj GV, Panageas KS. How to build and interpret a nomogram for cancer prognosis. J Clin Oncol. 2008 Mar 10;26(8):1364-70. doi: 10.1200/JCO.2007.12.9791. Review. — View Citation

Klimstra DS, Modlin IR, Adsay NV, Chetty R, Deshpande V, Gönen M, Jensen RT, Kidd M, Kulke MH, Lloyd RV, Moran C, Moss SF, Oberg K, O'Toole D, Rindi G, Robert ME, Suster S, Tang LH, Tzen CY, Washington MK, Wiedenmann B, Yao J. Pathology reporting of neuro — View Citation

Klöppel G, Perren A, Heitz PU. The gastroenteropancreatic neuroendocrine cell system and its tumors: the WHO classification. Ann N Y Acad Sci. 2004 Apr;1014:13-27. Review. — View Citation

Klöppel G, Rindi G, Perren A, Komminoth P, Klimstra DS. The ENETS and AJCC/UICC TNM classifications of the neuroendocrine tumors of the gastrointestinal tract and the pancreas: a statement. Virchows Arch. 2010 Jun;456(6):595-7. doi: 10.1007/s00428-010-092 — View Citation

Modlin IM, Champaneria MC, Bornschein J, Kidd M. Evolution of the diffuse neuroendocrine system--clear cells and cloudy origins. Neuroendocrinology. 2006;84(2):69-82. Epub 2006 Nov 9. Review. — View Citation

Modlin IM, Gustafsson BI, Pavel M, Svejda B, Lawrence B, Kidd M. A nomogram to assess small-intestinal neuroendocrine tumor ('carcinoid') survival. Neuroendocrinology. 2010;92(3):143-57. doi: 10.1159/000319784. Epub 2010 Aug 23. — View Citation

Modlin IM, Lye KD, Kidd M. A 5-decade analysis of 13,715 carcinoid tumors. Cancer. 2003 Feb 15;97(4):934-59. — View Citation

Modlin IM, Oberg K, Chung DC, Jensen RT, de Herder WW, Thakker RV, Caplin M, Delle Fave G, Kaltsas GA, Krenning EP, Moss SF, Nilsson O, Rindi G, Salazar R, Ruszniewski P, Sundin A. Gastroenteropancreatic neuroendocrine tumours. Lancet Oncol. 2008 Jan;9(1) — View Citation

Modlin IM, Shapiro MD, Kidd M. Siegfried Oberndorfer: origins and perspectives of carcinoid tumors. Hum Pathol. 2004 Dec;35(12):1440-51. — View Citation

Niederle B, Pape UF, Costa F, Gross D, Kelestimur F, Knigge U, Öberg K, Pavel M, Perren A, Toumpanakis C, O'Connor J, O'Toole D, Krenning E, Reed N, Kianmanesh R; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Neuroendocri — View Citation

Pape UF, Niederle B, Costa F, Gross D, Kelestimur F, Kianmanesh R, Knigge U, Öberg K, Pavel M, Perren A, Toumpanakis C, O'Connor J, Krenning E, Reed N, O'Toole D; Vienna Consensus Conference participants. ENETS Consensus Guidelines for Neuroendocrine Neop — View Citation

Pavel M, O'Toole D, Costa F, Capdevila J, Gross D, Kianmanesh R, Krenning E, Knigge U, Salazar R, Pape UF, Öberg K; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for the Management of Distant Metastatic Disease of Intestinal, — View Citation

Peczkowska M, Erlic Z, Hoffmann MM, Furmanek M, Cwikla J, Kubaszek A, Prejbisz A, Szutkowski Z, Kawecki A, Chojnowski K, Lewczuk A, Litwin M, Szyfter W, Walter MA, Sullivan M, Eng C, Januszewicz A, Neumann HP. Impact of screening kindreds for SDHD p.Cys11 — View Citation

Ramage JK, De Herder WW, Delle Fave G, Ferolla P, Ferone D, Ito T, Ruszniewski P, Sundin A, Weber W, Zheng-Pei Z, Taal B, Pascher A; Vienna Consensus Conference participants. ENETS Consensus Guidelines Update for Colorectal Neuroendocrine Neoplasms. Neuro — View Citation

Rindi G, Klöppel G, Couvelard A, Komminoth P, Körner M, Lopes JM, McNicol AM, Nilsson O, Perren A, Scarpa A, Scoazec JY, Wiedenmann B. TNM staging of midgut and hindgut (neuro) endocrine tumors: a consensus proposal including a grading system. Virchows Ar — View Citation

Washington MK, Tang LH, Berlin J, Branton PA, Burgart LJ, Carter DK, Compton CC, Fitzgibbons PL, Frankel WL, Jessup JM, Kakar S, Minsky B, Nakhleh RE; Members of the Cancer Committee, College of American Pathologists. Protocol for the examination of speci — View Citation

* Note: There are 20 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	PFS - Progression Free Survival	the time from the start of systemic treatment date to the date of first documented disease progression (event: disease progression - DP, based on RECIST, death, adverse events, which provide to disqualification from further therapy). Patients without progression at the time of analysis will be censored.	7 years
Primary	OS - Overall Survival	is defined as the time from the start of systemic treatment date to the date of death due to any cause or the date of last contact (censored observation) at the date of data cut-off.	7 years
Secondary	Log-rank test	assessment of differences in survival of patients between subgroups	7 years
Secondary	Cox proportional-hazards model	uni- and multivariate analyses used for investigating the association between the survival time of patients and prognostic factors	7 years