Neoplasms

All Conditions

Rare Diseases

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Neuroendocrine Tumor

Neuroepithelioma

Surgery

The purpose of this study is to evaluate the effect of different surgical resections (R0, R1, R2) on circulating NET transcripts (PCR score or NETest). A drop in circulating NET levels will be correlated with surgical excision. Secondly, variation of circulating NET transcripts will be correlated to NET recurrence to test whether this analysis may constitute an early predictive marker of disease relapse.

Biomarker-based tools that can accurately predict gastroenteropancreatic neuroendocrine tumor (GEP-NET) treatment response and tumor recurrence are currently not available. Circulating biomarkers that are associated with GEP-NETs are limited to measurements of plasma chromogranin A (CgA). The investigators have developed a PCR-based tool to quantitate (score) the circulating GEP-NET molecular signature ("liquid" biopsy) with high sensitivity and specificity. This signature can identify all types of GEP-NETs including small (1cm) non-metastatic tumors, is significantly reduced after tumor debulking and is decreased following surgical "cure". Elevated post-surgical scores are associated with tumor recurrence within 6 months in \~40% of cases. Current NET treatment protocols are associated with tumor recurrence (progression free survival) ranging from 5-18 months. The majority of patients will experience a relapse within 18 months irrespective of the treatment approach. The investigators hypothesize that a PCR measurement of circulating NET mRNA can accurately predict the extent of surgical resection (tumor removal) and elevated scores can predict tumor relapse before this occurs. This biomarker protocol seeks to test this hypothesis and evaluate whether changes in plasma CgA are as effective in predicting resection and recurrence.

Surgical Intervention and the NETest

Diagnosis of Neuroendocrine Neoplasms and Assessment of Response to Surgery by Means of Measurement of Gene Transcripts in Blood

Analysis of the change in biomarker scores (from baseline to post-surgical levels at 1 month) will be utilized to establish the strength of the relationship between the biomarker and volume of tumor removed (cm3).

Analysis of the alterations in the biomarker levels (from post-surgical levels, i.e., month 1) will be utilized to establish when the disease status has altered; a sustained increase in score will be recorded and compared with imaging to assess whether this is associated with disease progression/recurrence.

Biomarker scores will be compared to the frequency of clinical symptoms, specifically flushing, to assess whether there is a relationship.

Biomarker scores will be compared to the frequency of clinical symptoms, specifically diarrhea, to assess whether there is a relationship.

Wren Laboratories LLC

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma

Carcinoma, Neuroendocrine

Lung Neoplasms

Neoplasms, Glandular and Epithelial

Adenocarcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Carboplatin

Etoposide

Cisplatin

Etoposide phosphate

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Pembrolizumab 200mg IV day 1 with Carboplatin AUC 6 IV day 1 or Cisplatin 80mg/m2 day 1 with etoposide 100mg/m2 days 1-3 of 21 day cycle. Repeat 4-6 cycles to be followed by maintenance Pembrolizumab 200mg IV day 1 every 21 days until progression or intolerance for up to 2 years.

Intravenous administration of pembrolizumab in combination with cisplatin or carboplatin and etoposide in first line metastatic or unresectable high grade neuroendocrine carcinoma:

Robert Ramirez, DO

The purpose of this study is to test the efficacy, safety, and tolerability of the combination of chemotherapy treatment, which could be either Cisplatin or carboplatin and etoposide, and the research study drug, Pembrolizumab (also known as MK-3475) in patients with high grade neuroendocrine carcinomas of the gastroenteropancreatic system or lung who are chemotherapy naïve. The chemotherapy treatment you receive will be either Cisplatin or carboplatin and etoposide. the participant's doctor will discuss this choice with you and determined which chemotherapy treatment is best for you.

Combination chemotherapy is the mainstay of treatment for patients with high grade GEPNETs and neuroendocrine carcinomas of the lung.

This study will utilize pembrolizumab, a potent humanized immunoglobulin G4 (IgG4) monoclonal antibody (mAb) with high specificity of binding to the programmed cell death 1 (PD-1) receptor, thus blocks a protective mechanism of cancer cells and thereby allows the immune system to destroy them, in combination with chemotherapy.

Combination chemotherapy and pembrolizumab was recently FDA approved and ongoing trials are utilizing this or similar combination with preliminary data demonstrating a promising safety profile.

Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma

A Phase II Trial of Pembrolizumab in Combination With Cisplatin or Carboplatin and Etoposide in Chemotherapy naïve Patients With Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung (Excluding Small Cell) Neuroendocrine Carcinoma

Assessed by investigator using Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Merck Sharp & Dohme LLC

Ochsner Health System

Principal Investigator

Anti-Infective Agents

Everolimus

Temozolomide

Antineoplastic Agents, Alkylating

Alkylating Agents

Sirolimus

Temsirolimus

MTOR Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Immunosuppressive Agents

Immunologic Factors

Everolimus 10 mg daily, temozolomide 150 mg/m2 for 7 days every 2 weeks.

Everolimus , temozolomide

Halfdan Sorbye, MD

To study the efficacy of everolimus combined with temozolomide as first-line treatment in advanced gastroenteropancreatic neuroendocrine carcinoma with a Ki67 of 20-55%, measured as disease control rate (non-progressive disease) at 6 months.

Guidelines for treating advanced gastroenteropancreatic neuroendocrine carcinomas (GEP-NECs) advocate the use of combination chemotherapy with a platinum-based chemotherapy combined with etoposide. No other regimen has consistently shown a benefit over this combination. NECs do not respond to treatments usually applied in other neuroendocrine tumours such as somatostatin analogues and interferon. In contrast to metastatic neuroendocrine tumours with a low Ki67, debulking surgery and surgery for liver metastasis is generally not recommended. Cisplatin /carboplatin and etoposide is established as standard treatment of advanced disease based on two small retrospective studies showing a response rate between 41- 67% and median survival of 15-19 months. In the current trial we propose an alternative treatment for a subgroup of patients with GEP-NEC based on new data, with the intention to improve response rates and clinical benefit rate without increasing toxicity

Everolimus and Temozolomide in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3)

Everolimus and Temozolomide as 1-line Treatment in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3) With a Ki67 of 20-55%

Patients alive at 18 months after last patient entered into the study will be censored.

Especially number of patients with grade 3-4 toxicity.

Skane University Hospital

Copenhagen University Hospital, Denmark

Rigshospitalet, Denmark

Uppsala University Hospital

Aarhus University Hospital

Sahlgrenska University Hospital, Sweden

Ullevaal University Hospital

Haukeland University Hospital

Carcinoid Tumor

Gastrointestinal Agents

Somatostatin

Octreotide

Pasireotide

Antineoplastic Agents, Hormonal

Hormones

Hormone Antagonists

Patients assigned to pasireotide LAR will receive a 60 mg dose of pasireotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 40 mg is permitted if tolerability issues arise. In addition, after 24 hours of the first LAR injections the patients were permitted to use pasireotide s.c. formulation for breakthrough symptoms as needed.

Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.

Pasireotide LAR 60mg i.m. injection - patients may also receive pasireotide 600 µg s.c 3 times a day for symptom control as needed

Octreotide LAR 40mg i.m. depot injection - Patients may also receive octreotide 100 µg s.c. 3 times a day for symptom control as needed

Novartis Pharmaceuticals

The purpose of this randomized, multicenter, Phase III study was to compare the efficacy of paseriotide LAR and octreotide LAR in patients whose disease-related symptoms are inadequately controlled by currently available somatostatin analogues.

Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease

A Multicenter, Randomized, Blinded Efficacy and Safety Study of Pasireotide LAR vs Octreotide LAR in Patients With Metastatic Carcinoid Tumors Whose Disease-related Symptoms Are Inadequately Controlled by Somatostatin Analogues.

Percentage of patients who received clinical benefit in symptom (diarrhea and/or flushing) improvement as: Diarrhea (D)+Flushing (F): Patients with a daily mean number (#) of at least four bowel movements and a total of five or more flushing episodes. Clinical Benefit Response Criteria (CBRC): \<4 daily mean bowel movements AND at least 20% reduction from Baseline in the daily mean # of bowel movements AND any reduction in the total # of flushing episodes compared with Baseline. (D) Patients with a daily mean # of at least four bowel movements and a total # of \<5 flushing episodes. (CBRC) \<4 daily mean bowel movements AND at least a 20% reduction from Baseline in the daily mean # of bowel movements. (F) Patients with a total # of at least 14 flushing episodes and a daily mean # of \<4 bowel movements (CBRC) At least a 30% reduction from Baseline in the total # of flushing episodes.

Percent change from Baseline in mean daily bowel movements at Month 6 were compared between the two treatment groups using ANCOVA model with treatment as the main effect and symptom levels at Baseline (e.g. mean daily bowel movement at Baseline) and randomization stratum (D+F or D) as covariates. Percentage change = (Month 6 - baseline)/baseline.

Percent change from Baseline in total number of flushing episodes comprising Month 6 were compared between the two treatment groups using ANCOVA model with treatment as the main effect and symptom levels at Baseline (e.g. total number of flushing episodes at Baseline) and randomization stratum (D+F or F) as covariates.

Baseline evaluations were to include Triphasic CT scan or MRI of the abdomen. Triphasic CT or MRIs were to be read by same radiologist at each assessment, measuring the same target and non-target lesions and accounting for all lesions that were present at Baseline. All known disease was accounted for when assessing objective tumor status. Current objective tumor status was to be captured on Tumor Assessment CRF. Objective response rate was defined by RECIST criteria: Partial response (PR) must have ≥ 30% decrease in the sum of longest diameter of all target lesions, from the baseline sum. Complete response (CR) must have disappearance of all target and non-target lesions. For CR or PR, tumor measurements must be confirmed by 2nd assessments within 4 weeks. Progression = 20% increase in the sum of longest diameter of all target lesions, from smallest sum of longest diameter of all target lesions recorded at or after baseline; or a new lesion; or progression of non-target lesions.

Disease control rate (DCR) is the proportion of patients with a best overall response of Complete Response (CR) or Partial Response (PR) or Stable Disease (SD). Complete Response (CR): Disappearance of all target lesions Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of all target lesions, taking as reference the baseline sum of the longest diameters. Progressive Disease (PD): At least a 20% increase in the sum of the longest diameter of all measured target lesions, taking as reference the smallest sum of longest diameter of all target lesions recorded at or after baseline, or a new lesion; or progression of non-target lesions. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR or CR nor an increase in lesions which would qualify for PD. Unknown (UNK) Progression has not been documented and one or more target lesions have not been assessed or have been assessed using a different method than baseline.

Pasireotide LAR

Patients assigned to octreotide LAR will receive a 40mg dose of octreotide LAR i.m. depot injection once every 28 days (+/- 3 days) for 6 months at visits 2, 4, 5, 6, 7 and 8. A dose reduction to 30 mg is permitted if tolerability issues arise. Patients requiring a dose reduction are to return to the higher dose once the tolerability issue is resolved, if required for efficacy. In addition, after 24 hours of the first LAR injections the patients were permitted to use octreotide s.c. formulation for breakthrough symptoms as needed.

Octreotide LAR

Extension Phase Pasireotide LAR

Extension Phase Octreotide LAR

After 6 month double blind core period, non-responders on Octreotide were given option to cross over to Pasireotide LAR in the Extension Phase of study.

Crossover to Pasireotide LAR

Total

Age Continuous

Sex: Female, Male

Study Director

Diarrhea and Flushing (N=37, 39)

Diarrhea (N=2, 5)

Flushing (N=4, 1)

Overall (N=43, 45)

The Efficacy analyzable set consists of subset of FAS patients who were randomized at least six months prior to futility interim analysis data cut-off. It is for the primary efficacy analysis and secondary efficacy analysis except for tumor response assessment. Data reported was based on randomized patients at the time of the interim analysis.

Percentage of Patients Who Achieved Clinical Symptom Improvement by Randomization Stratum and Treatment.

Diarrhea and Flushing (N=24, 28)

Predominantly Diarrhea (D) (N=2, 4)

Overall (N=26, 32)

The Efficacy analyzable set consists of the subset of FAS patients who were randomized at least six months prior to the futility DMC data cut-off. Patients who had symptoms at baseline and at 6 months were included in this analysis.

Improvement in Daily Mean Number of Diarrhea Bowel Movement Episodes by Randomization Stratum and Treatment.

Predominately Flushing (N=4, 1)

Overall (N=28, 29)

The Efficacy analyzable set consists of the subset of FAS patients who were randomized at least six months prior to the futility DMC data cut-off. Patients were analyzed according the treatment they were assigned to at randomization. (ITT) principle.

Improvement in Daily Mean Number of Flushing Episodes by Randomization Stratum and Treatment.

This Outcome Measure was planned in the protocol but not included in the analysis due to early termination of study due to lack of efficacy in symptom control.

Pasireotide LAR vs. Octreotide LAR on Time to Symptom Response.

Full Analysis Set (FAS) consists of all patients randomized into the study. Patients were analyzed according to the treatment they were assigned to at randomization. Patients randomized 6 months before the final clinical cutoff date were included in this analysis.

Objective Tumor Response Rate Assessed by Investigator

Full Analysis Set (FAS) consists of all patients randomized into the study. Following the intent-to-treat principle, patients were analyzed according to the treatment they were assigned to at randomization. Patients with analyzable data at month 6 were included in this analysis.

Pasireotide LAR vs. Octreotide LAR on Disease Control Rate Based on RECIST Criteria

Pasireotide LAR vs. Octreotide LAR on Quality of Life Assessed by FACIT-D Questionnaire

Pasireotide LAR vs. Octreotide LAR on Time to Symptom Progression

Pasireotide LAR vs. Octreotide LAR on Duration of Symptom Response

Assess the Proportion of Patients Who Achieved at Least a 30% Reduction in Frequency of Bowel Movements

Extension: Octreotide LAR/Pasireotide LAR

Core Phase

Extension Phase

Behaviors and Mental Disorders

Aggression

Gastro-enteropancreatic Neuroendocrine Tumor

Pharmaceutical Solutions

Micronutrients

Hematinics

Vitamins

Amino Acids

Capecitabine

Leucovorin

Fluorouracil

Levoleucovorin

Oxaliplatin

Folic Acid

Edotreotide

Edotreotide lutetium LU-177

Vitamin B Complex

Antimetabolites

Antidotes

Protective Agents

Trace Elements

Radiopharmaceuticals

Folinic Acid

Arginine

Folate

Vitamin B9

Lysine

Peptide Receptor Radionuclide Therapy (PRRT) using 177Lu-edotreotide with a defined number of cycles will be administered.

177Lu-Edotreotide (Peptide Receptor Radionuclide Therapy) PRRT

Best standard of care treatment (investigator's choice \[from the protocol comparator list\]) according to individual risk-benefit assessment, institutional protocols, the local Prescribing Information, local regulations, or the local guidelines.

CAPTEM (Capecitabine and Temozolomide)

The Amino-Acid Solution (AAS) to be used in this study will contain a mixture of lysine and arginine diluted in an electrolyte solution.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Surgical Intervention and the NETest	NCT03012789	Neuroendocrine ... Gastroenteropan...	Surgery	18 Years -	Wren Laboratories LLC
Pembrolizumab With Chemotherapy in Metastatic or Unresectable High Grade Gastroenteropancreatic or Lung Neuroendocrine Carcinoma	NCT03901378	Neuroendocrine ... Large Cell Neur... High Grade Neur...	Pembrolizumab	18 Years -	Ochsner Health System
Everolimus and Temozolomide in Advanced Gastroenteropancreatic Neuroendocrine Carcinoma (G3)	NCT02248012	Neuroendocrine ...	Everolimus , te...	18 Years -	Haukeland University Hospital
Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease	NCT00690430	Symptomatic Ref...	Pasireotide Octreotide	18 Years -	Novartis
Lutetium 177Lu-Edotreotide Versus Best Standard of Care in Well-differentiated Aggressive Grade-2 and Grade-3 GastroEnteroPancreatic NeuroEndocrine Tumors (GEP-NETs) - COMPOSE	NCT04919226	Neuroendocrine ...	177Lu-Edotreoti... CAPTEM (Capecit... Amino-Acid Solu... Everolimus FOLFOX (Folinic...	18 Years -	ITM Solucin GmbH
Efficacy and Safety of Pasireotide Long Acting Release vs. Octreotide Long Acting Release in Patients With Metastatic Carcinoid Disease	NCT00690430	Symptomatic Ref...	Pasireotide Octreotide	18 Years -	Novartis
Surgical Intervention and the NETest	NCT03012789	Neuroendocrine ... Gastroenteropan...	Surgery	18 Years -	Wren Laboratories LLC

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