Ignite Creation Date:
2024-05-06 @ 12:54 PM
Last Modification Date:
2024-10-26 @ 1:05 PM
Study NCT ID:
NCT03870399
Status:
COMPLETED
Last Update Posted:
2024-05-06
First Post:
2019-03-06
Brief Title:
Study of Tamoxifen in Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression
Sponsor:
AC Camargo Cancer Center
Organization:
AC Camargo Cancer Center
Study Overview
Official Title:
Phase II Study of Hormone Therapy With Tamoxifen in Patients With Well Differentiated Neuroendocrine Tumors and Hormone Receptor Positive Expression
Status:
COMPLETED
Status Verified Date:
2024-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
HORMONET
Brief Summary:
This is a single-arm unicentric single-stage clinical study of tamoxifen for patients with well differentiated neuroendocrine tumors and radiological progression with positive 1 percent HR estrogen and or progesterone expression by IHC It will evaluate if Tamoxifen exerts antitumor action in patients with well differentiated NET and positive for the expression of HR estrogen and or progesterone
Detailed Description:
Neuroendocrine tumors NET are rare neoplasms but with increasing incidence and prevalence in the last decades Although they may manifest in the most diverse tissues the vast majority of cases will affect organs of the digestive tract and lung At diagnosis more than half of the cases present metastatic disease and among patients with localized disease up to one-third will have recurrence of the disease Unfortunately the minority of patients with metastatic disease are eligible for curative intent Although there are many types of NET they are often studied together as a group because their cells share common histological findings have special secretory granules and the ability to secrete bioactive amines and polypeptide hormones Approximately 25 percent of the tumors present functional hormonal syndromes situation of great morbidity for these patients being the carcinoid syndrome the most common one From the molecular point of view these neoplasias are largely dependent on the activation of the mTOR pathway and neoangiogenesis Another striking feature of neuroendocrine cells is the expression of cell surface hormone receptors whose activation or blockade may exert an important regulatory function The discovery of somatostatin and consequently its receptors is one of the major advances in the treatment of this neoplasm Due to the increased ability of somatostatin to inhibit the secretion of several hormones its antitumor property has long been studied However only after the development of synthetic long-life formulations can their use be used in clinical practice Well-differentiated neuroendocrine tumors G1 and G2 according to World Health Organization WHO classification present in more than 80 percent of somatostatin receptor cases In this population the use of somatostatin analogues promotes symptomatic improvement of functioning syndromes in the order of 70 to 77 percent and biochemical improvement around 50 percent Regarding antiproliferative activity two phase III studies evaluated the role of octreotide LAR and of lanreotide autogel both somatostatin analogs in the population of well differentiated tumors and almost entirely somatostatin receptor hyperexpressors when evaluated by octreoscan In these studies the use of somatostatin analogue was associated with reduced risk of progression or death from 53 percent to 66 percent when compared to placebo Currently this class of drugs is often considered as the first treatment option for patients with progressing metastatic disease when the strategy of watchful waiting is not opted for because they are tumors of sometimes indolent behavior some cases are selected for observation only In general there are few options for systemic therapies that are approved for these tumors in addition to somatostatin analogs mTOR and antiangiogenic inhibitors none of which clearly demonstrate overall survival gain are costly and none are available for use in the public health system SUS Therefore it is very important to develop studies with new therapies for patients with NET especially molecularly defined therapies with greater access to patients In this context other anti-hormonal therapies could be explored in patients with NET such as the role of the sex hormones estrogen and progesterone as well as their receptors A few studies have evaluated the expression of estrogen and progesterone receptors in NET and suggest interesting results One of the largest series was conducted at the AC Camargo Cancer Center where the immunohistochemical expression of these receptors was evaluated in 96 patients with NET from various sites About 35 percent of the cases presented positivity for some hormonal receptor HR in the tumor tissue Among the HR positive cases there was no difference between sex more frequent in thin pancreatic and lung tumors and in well differentiated tumors G1 and G2 by the WHO Viale et al Evaluated the expression of progesterone receptors PR in 96 patients with pancreatic neuroendocrine tumors Nuclear immunoreactivity for PR was observed in 58 percent of cases with no difference in PR expression according to gender age or functioning syndromes About 163 primary tumors of the gastroenteropancreatic site and 115 metastases were evaluated by Zimmermann and colleagues for expression of female hormone receptors Progesterone receptor was more frequently found in pancreatic tumors and rarely in non-pancreatic p 0001 estrogen receptor was more frequently expressed in non-pancreatic tumors 0001 and in women p 0019 There was no difference between primary site and presence of metastases Apparently HR positive tumors may present a more favorable evolution A study evaluated 160 patients with pancreatic neuroendocrine tumors operated for expression by PTEN immunohistochemistry negative regulator of the mTOR pathway and PR Approximately 69 percent of the cases were positive for PR and PTEN 28 percent were positive for one of the two markers and only 3 percent were negative for both Combined positivity for PTEN and PR was associated with metastasis-free survival in stages I and II p 0001 and overall survival in all patients p 0001 even after adjustment for other prognostic variables Patients with negative PR and PTEN tumors had the shorter survival times when compared to those who had only one or both markers p 0001 9 Similarly other author demonstrated a retrospective analysis of 277 patients with neuroendocrine tumors 95 percent vs 76 percent p 005 and a higher survival rate p 005 than in the control group p 005 0015 Even rarer in the literature is the role of antiestrogen therapies as a form of control of this neoplasia Case reports point to antiproliferative activity of tamoxifen in patients with NET and in some cases patients presenting more than 12 months of disease control11 Reports of control of carcinoid syndrome and even regression of associated retroperitoneal fibrosis have also been described However the only study to assess the activity of tamoxifen in neuroendocrine tumors dates back to 1984 Sixteen patients were evaluated clinical benefit in only 19 percent of cases and no radiological response However in this study no patient was previously selected for HR tumor expression or degree of differentiation which the investigators believe limited benefit in disease control Therefore based on the premise that there is a need for research and treatment strategies for this rare neoplasm there is clear therapeutic embezzlement in the public heath system due to the high cost of the treatments approved in the country for this neoplasia NET are tumors that may present positivity to estrogen and or progesterone receptors evidence points to the possibility of antiproliferative effect using hormonal therapy the investigators propose a phase II study of tamoxifen for patients with well differentiated NET and positive for HR estrogen and or progesterone expression
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None