Neoplasms

All Conditions

Gland and Hormone Related Diseases

Rare Diseases

Carcinoma

Thyroid Neoplasms

Thyroid Diseases

Endocrine System Diseases

Endocrine Gland Neoplasms

Head and Neck Neoplasms

Thyroid Cancer, Medullary

All Drugs and Chemicals

Bone Density Conservation Agents

Vasodilator Agents

Gastrointestinal Agents

Antihypertensive Agents

Sacubitril and valsartan sodium hydrate drug combination

Calcitonin

Salmon calcitonin

Calcitonin Gene-Related Peptide

Katacalcin

Gastrins

Cholecystokinin

Valsartan

Angiotensin Receptor Antagonists

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N without and second injection with additional medication of Sacuitril (100 mg Entresto)(crossover)

First intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and second injection without additional medication of Sacuitril (100 mg Entresto)(crossover)

Intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without co-medication with Sacuitril (100 mg Entresto) in each patient

177Lu-PP-F11N

Medication with Sacuitril (100 mg Entresto) additional to the injection of 177Lu-PP-F11N

Sacuitril

Christof Rottenburger, Dr. med.

Damian Wild, PhD Dr

The purpose of this study is to determine the use of 177Lu-PP-F11N for imaging and therapy of patients with advanced medullary thyroid carcinoma (MTC). 177Lu-PP-F11N is a gastrin analogon, binding to cholecystokinin-2 receptors. This receptors show an overexpression on more than 90 % of medullary thyroid carcinomas.

A phase 0 study (Lumed study part A) was already performed, showing low toxicity of 177Lu-PP-F11N and tumor uptake in all patients. Co-injection of Physiogel (Gelofusin) showed insignificant reduction of kidney uptake and can therefore be omitted for a radionuclide therapy with 177Lu-PP-F11N. In this study, the effect of the NEP-1 inhibitor Sacuitril on the in-vivo stability of 177Lu-PP-F11N and the uptake, respectively radiation doses in MTC metastases and organs will be evaluated, using a cross-over design already used for the Lumed part A study. Each patient will receive two injections of 177Lu-PP-F11N, with and without additional medication with Sacuitril Imaging findings, acquired by SPECT/CT, will be compared to imaging with 68Ga-DOTATOC positron emission tomography (PET)/CT. The inclusion of 8 patients is planned.

Group 1 patients will receive first 177Lu-PP-F11N alone, second 177Lu-PP-F11N in combination with Sacuitril. Group 2 patients will first receive 177Lu-PP-F11N in combination with Sacuitril, second 177Lu-PP-F11N alone. Affiliation of patients to Groups 1 and 2 will be randomised.

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer

177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer (Lumed Phase 0/B)

Chromogranin A blood values will be compared to the radiation doses of the stomach.

Comparison of tumor imaging by 68Ga-DOTATOC PET/CT and 177Lu-PP-F11N SPECT/CT

Evaluation of the radiation doses in tumor tissue from MTC after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Evaluation of the radiation doses in the kidneys and the tumor-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Evaluation of the radiation doses in other organs and the appropriate organ-to-kidney dose ratios after injection of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto)

Measurement (HPLC) of the in-vivo stability of 177Lu-PP-F11N alone and in combination with Sacuitril (Entresto).

In case of surgery with available tumor tissue samples, imaging results will be compared with autoradiographic analysis of somatostatine- and CCK2-receptor expression in tumor tissue.

Krebsforschung Schweiz, Bern, Switzerland

Center for Proton Therapy, Paul Scherrer Institute, Villigen,Switzerland

University Hospital, Zürich

University Hospital Freiburg

University Hospital, Basel, Switzerland

Thyroid Cancer, Papillary

Adenocarcinoma, Follicular

Adenocarcinoma

Adenocarcinoma, Papillary

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Papillary Thyroid Carcinoma

Thyroid Cancer, Follicular

Antineoplastic Agents

Amino Acids

Lenvatinib

Tyrosine Kinase Inhibitors

Sorafenib

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib.

SOC followed by Adaptive Care TKI Therapy for DTC Participants with \>=50% drop: Lenvatinib + Sorafenib.

Standard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib.

SOC followed by Adaptive Care TKI Therapy for MTC Participants with \>=50% drop: Cabozantinib + Vandetanib.

Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Cabozantinib

Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Vandetanib

Christine H. Chung, M.D.

Participants will have been diagnosed with advanced progressive thyroid cancer and are about to start treatment with a tyrosine kinase inhibitor (TKI).

The purpose of this study is to evaluate the efficacy and tolerability of tyrosine kinase inhibitor therapy (Lenvatinib or Sorafenib for differentiated thyroid cancer \[which includes papillary thyroid cancer, follicular thyroid cancer, and poorly differentiated thyroid cancer\]; and Cabozantinib or Vandetanib for medullary thyroid cancer) through adaptive (intermittent) versus conventional (continuous) regimen.

Population: Patients with advanced progressive 131I-refractory DTC or MTC will be enrolled to this study. Forty-five patients responding to TKI therapy (defined as 50% drop in tumor marker level within the first two months of treatment) will be randomized to receive TKI therapy either through adaptive (intermittent) or conventional (continuous) regimen.

Researchers consenting the patients will become unblinded upon treatment assignment.

Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer

Adaptive Tyrosine Kinase Inhibitor Therapy In Patients With Advanced Progressive Thyroid Cancer

Median time-to-discontinuation (TTD) of treatment per study arm, due to Progressive Disease.

Median time-to-discontinuation (TTD) of treatment per study arm, due to Intolerability.

Median time-to-discontinuation (TTD) of treatment per study arm, due to Disease-related death at 2 years.

The response rate will be estimated using binomial theory with Wilson's method for the 95% confidence interval. Complete Response (CR): Disappearance of all target lesions. Partial Response (PR): At least a 30% decrease in the sum of the longest diameter of target lesions, taking as reference the baseline sum longest diameter (LD). Stable Disease (SD): Neither sufficient shrinkage to qualify for partial response nor sufficient increase to qualify for progressive disease, taking as reference the smallest sum LD since the treatment started.

The median progression-free survival rates will be estimated from the Kaplan-Meier curve with the 95% confidence interval obtained from Greenwood's formula. Progressive Disease (PD): At least a 20% increase in the sum of the LD of target lesions, taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions.

The median overall survival rates will be estimated from the Kaplan-Meier curve with the 95% confidence interval obtained from Greenwood's formula.

H. Lee Moffitt Cancer Center and Research Institute

Standard of Care (SOC) TKI Therapy for Differentiated Thyroid Cancer (DTC): Lenvatinib + Sorafenib.

Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Standard of Care: DTC

SOC followed by Adaptive Care TKI Therapy for DTC Participants with \>=50% drop: Lenvatinib + Sorafenib.

Lenvatinib: Standard of Care: Lenvatinib 24 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Sorafenib: Standard of Care: Sorafenib 400 mg twice daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Adaptive Care: DTC

Standard of Care (SOC) TKI Therapy for Medullary Thyroid Cancer: Cabozantinib + Vandetanib.

Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Standard of Care: MTC

SOC followed by Adaptive Care TKI Therapy for MTC Participants with \>=50% drop: Cabozantinib + Vandetanib.

Cabozantinib: Standard of Care: Cabozantinib 140 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Vandetanib: Standard of Care: Vandetanib 300 mg daily. All participants will start receiving standard of care treatment.

Participants in the Adaptive Therapy regimen will receive TKI therapy in cycles: continuous treatment at the indicated dose until the patients' tumor marker (thyroglobulin in DTC or calcitonin in MTC patients) drops by ≥50% from the level at the time of enrollment ("baseline" level). A new cycle of TKI treatment will begin when/if the tumor marker increases to or above the "baseline" level.

Adaptive Care: MTC

Total

Age, Categorical

Sex: Female, Male

Ethnicity (NIH/OMB)

Race (NIH/OMB)

United States

Region of Enrollment

Christine Chung, MD

Data not collected. Only 3 participants remained on study treatment, and none for full length of trial.

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Progressive Disease

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Intolerability

Time to Tyrosine Kinase Inhibitor (TKI) Treatment Discontinuation Due to Disease Related Death

Overall Response Rate (ORR)

Progression-free Survival (PFS)

Overall Survival (OS)

Overall Study

Respiratory Tract (Lung and Bronchial) Diseases

Blood and Lymph Conditions

Lung Neoplasms

Neuroendocrine Tumors

Thymoma

Thymus Neoplasms

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms, Nerve Tissue

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Neuroendocrine Tumor

Neuroepithelioma

Hormones

Hormone Antagonists

Phase 0: 6 patients, intravenous application of 2 x 1 gigabequerel (GBq) 177Lu-PP-F11N with and without Physiogel (crossover)

Phase I: expected 12 - 18 patients, intravenous application of max. 6 x 7-8 GBq 177Lu-PP-F11N (increasing number of applications by one in groups of three patients). All patients with or without Physiogel, depending on the results of the phase 0 study.

Damian Wild, Prof Dr Dr

The purpose of this study is to determine the use of 177Lu-PP-F11N for imaging and therapy of patients with advanced medullary thyroid carcinoma (MTC). 177Lu-PP-F11N is a gastrin analogon, binding to cholecystokinin-2 receptors. This receptors show an overexpression on more than 90 % of medullary thyroid carcinomas.

In the pilot (phase 0) study investigators will correlate the tumour detection rate with the surgery and histology (proof of concept study). Furthermore, kidney protection and dosimetry studies will be performed in order to determine the kidney protection protocol and starting activity for the dose escalation study in the following, dose escalation (phase I) study. In the phase I study investigators will determinate the maximum tolerated dose of 177Lu-PP-F11N in patients with MTC. Furthermore, correlation with tumour radiation dose and treatment response as well as organ radiation doses and maximal tolerated dose will be performed in order to allow prospective individual patient tailored therapy planning. In the phase I study, participation is additionally possible for patients with well differentiated GEP-NET (grade 1-3) with a Ki67 index of up to 55% or NET of the lung or thymus (grade 1 and 2).

177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer.

177Lu-PP-F11N for Receptor Targeted Therapy and Imaging (Theranostics) of Metastatic Medullary Thyroid Cancer - a Pilot and a Phase I Study.

Phase 0 study: Evaluation of the scintigraphic visualisation of metastases after test injection, verification of 177Lu-PP-F11N uptake in metastases and correlation with surgery/histology if possible (poof of principle study).

Phase I study: Determination of the maximum tolerated dose (MTD)

Evaluation of the kidney radiation dose and the tumour-to-kidney radiation dose ratios with and without kidney protection (Physiogel). Composite measure.

Calculation of tumour and organ radiation doses.

Evaluation of in vivo stability of 177Lu-PP-F11N.

Measurement of the metabolites of 177Lu-PP-F11N with and without Physiogel infusion.

Evaluation of side reactions of 177Lu-PP-F11N.

Evaluation of biochemical response (decrease of calcitonin and calculation of calcitonin doubling time).

Evaluation of morphological therapy response (RECIST criteria).

Determination of the tumour detection rate and correlation with surgery/histology, if possible.

Calculation of organ radiation doses after therapy and correlation with the determined MTD (composite measure).

Determination of overall survival of patients after therapy.

Measurement of the metabolites of 177Lu-PP-F11N.

Digestive System Diseases

Pheochromocytoma

Paraganglioma

Neuroblastoma

Carcinoid Tumor

Insulinoma

Neuroectodermal Tumors, Primitive, Peripheral

Neoplasms, Neuroepithelial

Adenoma

Adenoma, Islet Cell

Pancreatic Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Pancreatic Diseases

Paragangliomas 1

Pancreatic Cancer

All patients will have their weight and baseline vital signs recorded.

The study subject will have an intravenous catheter inserted and receive a slow bolus intravenous dose of 185 - 370 MBq (5 -10mCi) 18F-FDOPA.

The patient will rest in a comfortable reclining chair in a warm, private shielded room for 45 to 60 minutes.

Patients are positioned supine and centered on the scanner bed for an average total scan time (CT and PET) of approximately 30 minutes.

Images will be interpreted by qualified and experienced physicians. Findings of significance from the PET/CT scan, and any incidental findings of significance from the CT scan, will be included in the single final report that will be issued to referring physicians.

[18 F]-6-L-fluorodihydroxyphenylalanine (18F-FDOPA)

Neuroendocrine tumours (NETs) are a group of neoplasms generally arising from the gastroenteropancreatic tract. They are usually slow growing, have low malignant potential, and often go unnoticed until they become metastatic. The correct treatment approach is dependent on the extent of the disease, however surgical approaches and systemic therapy can be curative.

Combined positron emission tomography/computed tomography (PET/CT) using the radiotracer 18F-6-L-fluorodihydroxyphenylalanine (18F-FDOPA) has been shown to be a promising non-invasive technique to help localizing NETs and guide their treatment.

Purpose/Objective:

The purpose of this study is to provide access to 18F-6-L fluorodihydroxyphenylalanine (18F-FDOPA) positron emission tomography and computed tomography (PET/CT) imaging to patients with neuroendocrine tumours (NET) and to collect additional data about the effectiveness of 18F-DOPA PET/CT in this patient population.

Hypothesis:

1. The overall accuracy of 18F-FDOPA PET/CT is superior to conventional imaging techniques for the detection of neuroendocrine tumours.
2. The sensitivity of 18F-FDOPA PET/CT is superior to conventional imaging techniques for the detection of neuroendocrine tumours.

Justification:

Treatment of NET's depends on the extent of disease and rate of tumour progression. Accurate staging is critical to establish the prognosis of the disease, to guide potentially curative surgical approaches and to assist in therapeutic decision making between surgery, embolization techniques and systemic therapy. Standard radiologic and nuclear medicine techniques all have significant limitations in terms of their ability to detect these lesions and to evaluate response to treatment. The widely used PET tracer 18F-Fluorodeoxyglucose (18-FDG) is of limited value in NET's due to its non-specific uptake and the relatively low mitotic rate often seen in these tumours.

Combined PET/CTutilizing 18F-FDOPA has been investigated as a potentially sensitive and specific staging and localization technique for NETs. Expression of tumour-specific catecholamine transport and storage mechanisms by NET cells is the basis of 18F-DOPA PET imaging. Cellular uptake and radiopharmaceutical concentration in intracellular storage granules within tumour cells of neuroendocrine origin and differentiation, combined with the high sensitivity, resolution and accurate anatomic localization of PET/CT imaging, makes 18F-DOPA PET/CT potentially superior to standard nuclear medicine and radiologic techniques for the detection and localization of functioning and non-functioning NETs. This imaging technique not only provides specific functional and biochemical information via PET images, but also morphological and anatomical detail via CT images leading to more accurate localization and characterization on individual lesions. This may allow better treatment planning as well as restaging during and after therapy to assess disease response. The information retrieved from the hybrid 18F-FDOPA PET/CT could have a profound influence on diagnosis and treatment of patients with NETs.

Research Method:

This will be an expanded access study in which adult and pediatric subjects will be invited to participate. All subjects are informed of anticipated effects (none) and purpose of the injected substance. Subjects are approached by their treating physicians with respect to their willingness to participate in the proposed study based on clinical criteria. They will then undergo a brief clinical assessment followed by the PET/CT scanning protocol.

The BC Cancer Agency anticipates a start date in August 2012 and a potential completion date August of 2017. Three full years of data collection will provide meaningful numbers for analysis. A total of 300 patients, including adults and pediatric patients, will be recruited for the study. This number is based on the anticipated number of PET scan referrals expected over a five-year study timeframe.

Statistical Analysis:

The primary outcomes will be estimates of sensitivity, specificity and accuracy of 18F-DOPA PET. 95% confidence intervals will be calculated for all estimates. Outcomes will be estimated for the whole study population and for different types of cancer.

Sensitivity (ratio of true positive lesions to total positive lesions), specificity (ratio of true negative lesions to total negative lesions) and accuracy (ratio of total correct studies to the total number of biopsied lesions) of 18F-FDOPA PET studies performed by the BCCA will be obtained by comparing results of the PET scan with the gold-standard of histopathological diagnosis when those results are available (as determined by clinical indication and feasibility by the treating physician) and results of conventional imaging. Biopsy of lesions is not mandated by this study. Confidence intervals (95% CI) for sensitivity, specificity and accuracy will be calculated using exact binomial distribution.

Results will be compared to figures in the published literature. All analyses will be performed in direct consultation with a statistician who is a member of the BC Cancer Agency staff.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer	NCT03647657	Thyroid Cancer,...	177Lu-PP-F11N Sacuitril	18 Years - 64 Years	University Hospital, Basel, Switzerland
Adaptive Tyrosine Kinase Inhibitor (TKI) Therapy In Patients With Thyroid Cancer	NCT03630120	Thyroid Cancer Thyroid Cancer,... Differentiated ... Papillary Thyro... Follicular Thyr... Poorly Differen...	Lenvatinib Sorafenib Cabozantinib Vandetanib	18 Years -	H. Lee Moffitt Cancer Center and Research Institute
177Lu-PP-F11N in Combination With Sacubitril for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer	NCT03647657	Thyroid Cancer,...	177Lu-PP-F11N Sacuitril	18 Years - 64 Years	University Hospital, Basel, Switzerland
177Lu-PP-F11N for Receptor Targeted Therapy and Imaging of Metastatic Thyroid Cancer.	NCT02088645	Thyroid Cancer,... Neuroendocrine ... Neuroendocrine ... Neuroendocrine ...	177Lu-PP-F11N	18 Years -	University Hospital, Basel, Switzerland
18F-FDOPA PET in Neuroendocrine Tumours	NCT02431715	Thyroid Cancer,... Carcinoid Tumor Pheochromocytom... Paraganglioma Insulinoma Neuroblastoma	[18 F]-6-L-fluo...	1 Month -	British Columbia Cancer Agency

Spots Global Cancer Trial Database for thyroid cancer, medullary