Symptoms and General Pathology

All Conditions

Neoplasms

Digestive System Diseases

Gland and Hormone Related Diseases

Nervous System Diseases

Heart and Blood Diseases

Rare Diseases

Syndrome

Pancreatic Neoplasms

Pituitary Diseases

Cushing Syndrome

Sarcoma, Ewing

Neuroectodermal Tumors, Primitive, Peripheral

Cardiac Complexes, Premature

Pituitary Neoplasms

ACTH Syndrome, Ectopic

Nelson Syndrome

Hypothalamic Diseases

Brain Diseases

Central Nervous System Diseases

Endocrine System Diseases

Gastrointestinal Neoplasms

Digestive System Neoplasms

Endocrine Gland Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Hypothalamic Neoplasms

Supratentorial Neoplasms

Brain Neoplasms

Central Nervous System Neoplasms

Nervous System Neoplasms

Adenoma

ACTH-Secreting Pituitary Adenoma

Paraneoplastic Syndromes

Adrenocortical Hyperfunction

Adrenal Gland Diseases

Pancreatic Cancer

Cushing's Syndrome

ACTH-secreting Pituitary Adenoma

Hyperadrenalism

All Drugs and Chemicals

Pasireotide

Hormones

Hormone Antagonists

Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase.

Investigational drug pasireotide LAR was supplied in vials with 20 mg or 40 mg powder and 2 mL vehicle was supplied in ampoules for reconstitution.

pasireotide LAR

Novartis Pharmaceuticals

This study will assess the effectiveness and safety of pasireotide long-acting release in patients who have rare tumors of neuroendocrine origin.

Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin

An Open Label, Multicenter, Single Arm Study of Pasireotide LAR in Patients With Rare Tumors of Neuroendocrine Origin

The primary efficacy endpoint was defined as the percentage of responders at Month 6 among pooled PNET patients (insulinoma, gastrinoma, VIPoma, and glucagonoma). A responder was defined as a patient who either attained normalization or had a greater than 50% reduction from baseline of the level of the primary biochemical tumor marker at Month 6 (M6). Four insulinoma pts were excluded from analysis because of unavailability of normal ranges for the associated primary biochemical tumor marker (insulin-to-glucose ratio). One patient with VIPoma with a normal baseline was also excluded. As a result, only 20 out of 25 patients with PNET were included in the assessment of the primary endpoint, which was less than the planned sample size of 34. Therefore, the primary objective could not be assessed with sufficient power. Patients with missing Month 6 assessment were considered as non-responders. Responder analyses are reported only for indications with minimum of 6 patients.

Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications.

Percentage of responders for each of the 10 NET indications considered in the study. Responder analyses were performed for an indication only if there were at least 6 patients in the efficacy analyzable set. For all other individual indications, the numbers of patients in the efficacy analyzable sets were less than 6 and therefore no responder analyses were carried out for these indications. The probability of success was a chance that the true responder rate was greater than 15%) for the indications gastrinoma, prolactinoma, and Nelson's syndrome.

Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6. One gastrinoma patient had a missing primary tumor marker value at Month 6, but had a Month 5 assessment done on Day 141, which fell within the allowed window period for Month 6.

Specific primary biochemical tumor markers were used to assess the efficacy of pasireotide in PNETs. A Month 6 responder was defined as the patients who either attained normalization or greater than 50% reduction from baseline in the level of the primary biochemical tumor marker at Month 6.

Six patients with Nelson's syndrome met the responder's criteria of attaining normalization or a reduction of more than 50% in primary tumor marker at Month 6.

Pancreatic NETs (PNETs)

Pituitary NETs (PiNETs)

Ectopic ACTH-secrting Tumors (EAS)

Nelson's syndrome is based on disease specific primary biochemical tumor markers. Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48.

Nelsons Syndrome

All patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase. Patients included patients with pancreatic neuroendocrine tumors (PNETs), pituitary NETs (PiNETs), Ectopic ACTH-secreting tumor (EAS) \& Nelson's syndrome.

Pasireotide LAR 60mg

Age, Continuous

Sex: Female, Male

The full analysis set (FAS) consisted of all enrolled patients who received at least one dose of pasireotide LAR.

Study Director

Gastrinoma

VIpoma

Glucagonoma

The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Patients with baseline primary biochemical tumor marker levels either missing at baseline or missing ULN or baseline value ≤ ULN were excluded.

Percentage of Responders at Month 6 - Pooled Pancreatic NETs (PNETs)

Prolactinoma

based on disease specific primary biochemical tumor markers. Patients received pasireotide LAR at 60 mg approximately once every 28 days for 6 months during the core treatment period and additional treatment cycles up to a total of 48 months during the extension phase.

Nelson's Syndrome

The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN.

Percentage of Responders at Month 6 - Individual NETs

Percentage of Responders With Probability of Success at Month 6 - Individual NETs

Baseline

Month 6

All PNETS (Gastrinoma)

The efficacy analyzable set included all enrolled patients who received at least one dose of pasireotide LAR and had indication-specific baseline primary biochemical tumor marker levels \>ULN. Responder analysis are reported only for indications with minimum of 6 patients. Patients with missing Month 6 assessment were considered as non-responders.

PNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker

All PiNETS (Prolactinoma)

PiNETs: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker

Nelson's syndrome is associated with local tumor extension or invasion following a therapeutic bilateral adrenalectomy

Nelson's Syndrome: Number of Patients Attaining Normalization or a More Than 50% Reduction in Primary Biochemical Tumor Marker

Overall Study

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Pancreatic Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

Temozolomide

Lenograstim

Mitogens

Antimetabolites

Antineoplastic Agents, Alkylating

Alkylating Agents

Part 1: dose-escalation phase to determine MTD of TAS-102 in combination with Temozolomide (TMZ). Treatment cycles are 28 days, with TAS-102 administered orally twice daily days 1-5 and 8-12, and TMZ administered orally days 8-12. No treatment medications administered days 13-28 of each cycle. Growth factor support is required during Part 1 and should be dosed per institutional standards.

Part 2: expansion phase to evaluate preliminary efficacy of MTD. Subjects treated with the recommended phase 2 drug doses determined in part 1. Treatment will continue for up to 13 cycles (approx. 12 months). Growth factor support is allowed during Part 2 and should be dosed per institutional standards.

TAS-102

Filgrastim provides growth factor support in multiple doses. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Filgrastim

Pegfilgrastim provides growth factor support in a single dose. It stimulates bone marrow to create neutrophils for patients undergoing chemotherapy.

Pegfilgrastim

Nataliya Uboha, MD

The goal of this study is to establish maximum tolerated doses/recommended phase 2 dose (RP2D) of temozolomide (TMZ) and TAS-102 when these agents are used in combination and to evaluate the safety profile of this drug combination.

The study is a two part phase 1B clinical trial consisting of three study periods: a screening period of 14 days or less, a treatment period, and a safety follow-up period 30 days after treatment discontinuation.

Part 1 is a dose finding phase with the objective to assess the safety and tolerability of the proposed drug combination and to identify the maximum tolerated dose (MTD) and a recommended phase 2 dose.

Part 2 is an open-label expansion study, which will enroll patients with metastatic pNETs who have not been previously treated with chemotherapy. Part 2 will obtain further safety data of the proposed drug combination.

Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs

Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic Neuroendocrine Tumors

Investigate the safety and determine the MTD of TAS-102 administered in combination with TMZ in patients with advanced NETs. Treatments will continue to disease progression according to Response Evaluation Criteria in Solid Tumors (RECIST).

Response rate defined as the percentage of subjects with a confirmed complete response (CR) or partial response (PR), assessed as per RECIST criteria. Assessments performed using RECIST criteria.

Defined as the time from the start of treatment to the date of first documented progression or any cause of death during the study, assessed according to RECIST. Analyzed using the Kaplan-Meier method.

Defined as the time from the start of treatment to the date of expiration. Analyzed using the Kaplan-Meier method.

Defined as the percentage of patients who achieved complete response, partial response, and stable disease by investigator assessment as per RECIST.

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

A major biochemical response will be defined as normalization or \>50% reduction in levels of Chromogranin A. Chromogranin A is elevated in up to 60% of functioning and nonfunctioning pancreatic endocrine tumors.

Taiho Pharmaceutical Co., Ltd.

University of Wisconsin, Madison

Capecitabine

7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 1 every 8 weeks for 4 cycles.

Oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 every 28 day cycle, up to 8 cycles.

7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV) on day 10 every 8 weeks for 4 cycles, with concurrent oral capecitabine 750mg/m2 b.i.d. days 1-14 and temozolomide 75mg/m2 b.i.d. days 10-14 up to 4 cycles.

7.8GBq 177Lu Octreotate (Lutate) given intravenously (IV)

octreotate

Nick Pavlakis, Associate Professor

Two parallel phase II randomized open label trials of Lutetium-177 Octreotate (177Lu-Octreotate) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemo): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade mid gut neuroendocrine tumours (mNETs).

PROTOCOL SYNOPSIS

Background

Neuroendocrine tumours (NETs) are a heterogeneous group of malignancies that can arise at any site in the gastrointestinal tract, that are known by their ability to over express somatostatin receptors. Originally called carcinoid tumours, these tumours are rising in incidence. In patients with incurable disease, several systemic options have demonstrated activity but few have been compared in prospective, randomised controlled trials (RCTs). 177Lu-Octreotate peptide receptor radionuclide therapy (PRRT) and CAPTEM have shown promising activity in initial single arm trials. Prospective RCTs are needed to build on these early trials to determine the optimal role of these therapies in clinical practice.

CONTROL NETs is a parallel group phase II randomised open label trial of Lutetium-177 Octreotate (177Lu-Octreotate (Lutate)) peptide receptor radionuclide therapy (PRRT) and capecitabine (CAP)/temozolomide (TEM) chemotherapy (chemotherapy): (i) versus CAPTEM alone in the treatment of low to intermediate grade pancreatic neuroendocrine tumours (pNETs); (ii) versus PRRT alone in the treatment of low to intermediate grade midgut neuroendocrine tumours (mNETs).

General aim

i) To determine the relative activity of CAPTEM/PRRT in biopsy-proven, low to intermediate grade, unresectable, metastatic 68Ga-octreotate PET-avid NETs in the following parallel phase II studies: Group A: pNETs and Group B: mNETs.

ii) To inform future comparative phase III RCTs to determine the optimal therapies in pNETs and mNETs.

Design

Two parallel non-comparative group randomised, controlled, multi-centre phase II, 2 arm open-label controlled trials with 2:1 allocation (experimental : control)

1. Study A: pNETs: PRRT/CAPTEM vs. CAPTEM (control)
2. Study B: mNETs: PRRT/CAPTEM vs. PRRT (control)

Randomisation will be performed using the method of minimisation.

Patients will be stratified by:

* Previous systemic therapy regimens (0,1 v 2)
* WHO tumour grade: Low Grade - G1 (Ki67\<3% (mitotic count \<2)) vs. Intermediate Grade - G2 (Ki67 3-20% (mitotic count 2-20))
* visceral only vs. visceral with bone metastases
* Treating institution

Population

The target population for this study is consenting adult patients with advanced, unresectable low or intermediate grade (Ki-67\<20%) midgut neuroendocrine tumours (mNETs) or pancreatic neuroendocrine tumours (pNETs ), who have received ≤ 2 prior systemic therapies for advanced unresectable disease (including long acting somatostatin analogues).

Assessments

* Patients will be assessed at each treatment cycle for toxicity
* CT including a 3 phase contrast CT of the liver will be undertaken at baseline, then every 2 months (pNET) or every 4 months (pNET) until radiologic progression by RECIST v1.1.
* 68Ga-DOTATATE PET CT Scan will be undertaken at baseline, then every 4 months until radiologic progression by RECIST v1.1.
* 18F-FDG PET Scan may be performed at the discretion of treating clinician at baseline, then every 2 months until radiologic progression by RECIST v1.1) for G2 NETS.
* 24-h whole-body planar gamma imaging will be undertaken on the day after administration of PRRT (every 2 months).
* Serum biomarkers will be undertaken every 4 months until disease progression.
* Quality of life assessments will be undertaken at every 2 months until disease progression using QLC C30 and QLQ-GINET21.
* Health utilities will be evaluated with EQ-5D-5L every 2 months until completion of study follow up.

Statistical considerations

Both studies are based on a Simon's two-stage design and are randomised using a 2:1 randomisation (Experimental: Control). A mix of approximately 30% G1 patients and 70% G2 patients is expected.

Study A, pNETs (n=90) will have 80% power with 95% confidence interval to exclude a 12 months PFS of 60% in favour of a more interesting rate of 77% in the experimental arm.

For Study B, mNETs (n=75), the PFS at 24 months in the control arm is expected to be 52%. Thus study B will have 80% power with 95% confidence interval to demonstrate a PFS rate at 24 months of 70% in experimental arm, a result that would warrant further investigation.

A total sample size of 165 patients for the two studies will be accrued over 2 years.

Patients will be followed up for a minimum of 2 years.

Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study

To correlate circulating \& tissue biomarkers with clinical study endpoints (relating to survival, response and safety), including but not limited to CgA, Ki-67 \& tumour MGMT expression.

Explore correlation between other measures of response relevant to this disease, eg 68Ga-DOTATATE, SUVmax tumour uptake, and other measures of response of a biochemical measure, eg. tumour markers, chromogranin A, and patient reported outcomes QOL undertaken in order to identify how progressive symptoms or biochemical response relates to conventional measures of response using structural and/or functional imaging. A formal statistical analysis plan will be formulated prior to final data analysis.

To determine the rate of progression free survival (PFS) at 12 months in pNETs (Group A), and at 24 months in mNETs (Group B). (PFS defined from time of randomisation to disease progression as defined by RECIST criteria version 1.1).

To determine objective tumour response rate (OTRR) (partial or complete response (PR/CR)).

To determine overall survival (OS) (death from any cause).

To determine safety (rates of adverse events).

To determine Quality of Life (QoL) (QoL scores from EORTC QLQ C30 and QLQ-GINET21 questionnaires)

To determine resource utilization (costs associated with treatment regimen, MBS and PBS data, and health utilities scores from EQ-5D-5L).

To evaluate the proportion of patients who have experienced a clinical benefit of the regimen(s). (Clinical Benefit is defined as the proportion of patients who experience complete or partial response (using RECIST v1.1) or stable disease at 12 months or 24 months as appropriate).

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin	NCT00958841	Pancreatic Neop... Pituitary Neopl... Nelson Syndrome Ectopic ACTH Sy...	pasireotide LAR	18 Years -	Novartis
Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs	NCT02943733	Neuroendocrine ... Neoplasms Cancer Tumors	TAS-102 Temozolomide Filgrastim Pegfilgrastim	18 Years -	University of Wisconsin, Madison
Study of Pasireotide in Patients With Rare Tumors of Neuroendocrine Origin	NCT00958841	Pancreatic Neop... Pituitary Neopl... Nelson Syndrome Ectopic ACTH Sy...	pasireotide LAR	18 Years -	Novartis
Capecitabine ON Temozolomide Radionuclide Therapy Octreotate Lutetium-177 NeuroEndocrine Tumours Study	NCT02358356	Midgut Neuroend... Pancreatic Neur...	octreotate Capecitabine Temozolomide	18 Years -	Australasian Gastro-Intestinal Trials Group
Safety of TAS-102 in Combination With Temozolomide for Metastatic Pancreatic NETs	NCT02943733	Neuroendocrine ... Neoplasms Cancer Tumors	TAS-102 Temozolomide Filgrastim Pegfilgrastim	18 Years -	University of Wisconsin, Madison

Spots Global Cancer Trial Database for pnets

Every month we try and update this database with for pnets cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for pnets

Every month we try and update this database with for pnets cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for pnets cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.