Neoplasms

Symptoms and General Pathology

All Conditions

Skin and Connective Tissue Diseases

Neoplasm Metastasis

Breast Neoplasms

Breast Diseases

Skin Diseases

All Drugs and Chemicals

Aromatase Inhibitors

Dr Sacha Howell, MD, PhD

Maria Ekholm, MD, PhD

Patients with metastatic breast cancer may respond well to treatment and metastases can remain stable for several years. Despite personalised medicine being increasingly used for diagnosis and treatment, follow-up still include radiological response evaluation every 3-4 months, which renders a significant number of 'unnecessary' exams for patients with long-term stable disease. Increasing evidence indicates that tumour markers such as circulating tumour DNA (ctDNA), thymidine kinase 1 (TK1) and cancer antigen 15-3 (CA15-3) may be useful for disease monitoring in the metastatic setting. However, algorithms that accurately define the time-points at which imaging can be foregone or reinstituted when progression is forecast, have not been developed. This study will measure ctDNA, TK1 and CA15-3 at all imaging time-points. The primary aim is to develop an algorithm based on these biomarkers, alone or in combination, that with sufficient specificity and sensitivity can advise whether a scan can be safely admitted at a specific time-point, for patients with MBC receiving first line therapy with AI plus cyclin dependent kinase 4/6 inhibitor (CDK4/6i). Additional samples will be stored such that novel biomarkers can also be tested in future. The cost-effectiveness of using the devised biomarker protocol will be evaluated.

One hundred patients with estrogen receptor positive (ER+)/ Human epidermal growth factor receptor negative (HER2-) metastatic or locally advanced breast cancer, eligible for 1st line endocrine therapy with AI + CDK4/6i will be included. Patients will receive standard therapy (AI + CDK4/6i) and follow-up will proceed according to local guidelines, namely cross sectional imaging with CT thorax/abdomen/pelvis +/- MRI as required and analysis of CA 15-3, every 3 cycles for the first year and every 3-4 cycles thereafter. Participation in the study will include serial blood sampling for the bespoke study biomarkers. Decisions on progression will be made according to the routine imaging tests and the biomarkers will be subsequently analysed.

The investigators hypothesise that the biomarkers ctDNA, TK1 and CA15-3, alone or in combination, will accurately correlate with disease status in patients receiving AI + CDK4/6i for metastatic breast cancer such that routine imaging can be delayed until predefined levels of biomarker progression.

Primary aim: To develop a biomarker-based prediction model to be used in patients with metastatic breast cancer, receiving first line therapy with AI and CDK4/6i, that provides the physician with a recommendation whether or not a radiological examination is required, based on the likelihood that the scan will actually show progressive disease.

Secondary aims

* To define the lead time between rising biomarker and subsequent progression on imaging
* To define the clinical utility of the bespoke biomarkers for disease monitoring
* The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring
* To define the economic impact of implementation of the chosen prediction model

Archived tumour tissue will be analysed using mutation panels to make personalised assays for circulating tumour DNA (dtDNA). ctDNA will be serially collected for subsequent analysis.

Personalised Disease Monitoring in Metastatic Breast Cancer

Personalised Disease Monitoring During Treatment With an Aromatase Inhibitor + Cyclin Dependent Kinase (CDK) 4/6 Inhibitor as 1st Line Endocrine Therapy in Patients With ER-positive/HER2-negative Metastatic Breast Cancer

ctDNA, CA15-3 and TK-1 assays will be performed at baseline, 2 weeks and at every imaging timepoint to develop a statistical algorithm to predict disease progression taht can be tested prospectively in future studies.

The relative value of analysing TK1 "on CDK4/6i treatment" versus "off CDK4/6i treatment" for disease monitoring

Cost effectiveness analysis of the using the prediction model

Sahlgrenska University Hospital, Sweden

The Christie NHS Foundation Trust

Blood and Lymph Conditions

Immune System Diseases

Rare Diseases

Lymphoma

Lymphoma, Follicular

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Lymphoma, Non-Hodgkin

Lymphosarcoma

Follicular Lymphoma

Patients with grades 1-2 or 3a follicular lymphoma (FL)

NCI Medical Oncology Referral Office

Mark J Roschewski, M.D.

For more information at the NIH Clinical Center contact National Cancer Institute Referral Office

Background:

Follicular lymphoma is a type of cancer of the lymph nodes. Lab studies are important for cancer research. They help scientists better understand differences in the cancer biology of different patients. Researchers want to collect serial samples over time from people with follicular lymphoma to help them design future treatments.

Objective:

To collect a variety of samples from people with follicular lymphoma to study how these diseases progress and respond to treatment.

Eligibility:

Adults at least 18 years old who have been diagnosed with, but have not yet had any treatment for, follicular lymphoma.

Design:

Participants will be screened with medical history and physical exam. They will answer questions about daily functioning. They will have blood and urine tests. They may have scans and have tissue samples taken.

Participants will be monitored about every 4 months for up to 2 years. They will repeat screening tests. They will have a cheek swab. A small brush will be rubbed against the inside of the cheek to wipe off some cells.

Participants will have imaging scans about every 8 months for up to 2 years.

Participants may have a bone marrow aspiration and biopsy. The hipbone will be numbed with a small needle.

A needle will be put into the hipbone, and about 2 tablespoons of bone marrow will be taken out through the needle.

Participants will continue being monitored every 6 months for up to 5 years, then 1 time a year.

Background:

* Follicular lymphoma (FL) is the second most common form of non-Hodgkin lymphoma and is incurable with standard first-line systemic therapy
* The clinical course of FL varies from slowly progressive over many years to a more rapid disease course that requires therapy shortly after diagnosis
* Early initiation of therapy does not improve survival, and asymptomatic patients are often managed with an initial period of watchful waiting
* Clinical prognostic indices predict survival, but cannot predict outcome for individual patients; biologic-based classifiers (gene-expression profiling and somatic mutational analyses) are more robust than clinical indices, but require prospective clinical validation from the time of diagnosis in the modern treatment era
* Paired samples linked to clinical information can lead to the discovery and/or validation of therapeutic targets for FL patients at the highest risk of early disease progression

Objective:

Characterize the molecular biology and clinical course of FL patients, and evaluate the time to treatment initiation for those patients who require first-line systemic therapy.

Eligibility:

* Follicular lymphoma (grade 1-2, 3a) with no evidence of histological transformation
* No previous cytotoxic, biologic or monoclonal antibody therapy for FL (previous radiation therapy permitted)
* Age greater than or equal to 18 years
* ECOG performance status of 0-2

Design:

* Patients with FL who meet all eligibility criteria will enroll on the study for expert monitoring of their disease, improved risk-stratification, and donation of tissue and cellular products for research. Patients will be monitored prospectively until they require second-line systemic treatment or the patient decides to withdraw from the study; untreated patients will be followed with clinic visits every 4 months for the first 2 years. After 2 years, protocol-specified visits will be increased to every 6 months until 5 years. After 5 years, protocol-specified visits will be annually until disease progression requiring first-line therapy.
* Patients without an indication for first-line systemic therapy at 2 years from initial study enrollment will be offered an optional biopsy of their lymph node and bone marrow.
* During first-line systemic therapy, patients can continue being monitored on this study for post-therapy clonal evolution. Protocol-specified visits after therapy will be every 6 months until 3 years. After 3 years, protocol-specified visits will be annually until disease progression requiring second-line therapy.
* Upon initiation of second-line therapy, if applicable, patients will move to survival follow-up only.

Clonal Evolution in Follicular Lymphoma

Prospective Study of Clonal Evolution in Follicular Lymphoma

.All IPD recorded in the medical record will be shared with intramural investigators upon request. @@@@@@All large scale genomic sequencing data will be shared with subscribers to dbGaP.

The types and frequency of each treatment will be reported.

Number of days from study enrollment until the date of initiation of first-line systemic treatment will be reported.

The number of days from initial diagnosis until date of first objective progression or death from any cause

The number of days from diagnosis to objective disease progression after first-line systemic treatment or death from any cause

The number of days from initiation of first-line systemic treatment to objective disease progression or death from any cause

The number of days from study enrollment until the date of initiation of second-line systemic treatment

The number of days from initial diagnosis until death from any cause

National Cancer Institute (NCI)

Heart and Blood Diseases

Multiple Myeloma

Neoplasms, Plasma Cell

Hemostatic Disorders

Blood Coagulation Disorders

Vascular Diseases

Paraproteinemias

Blood Protein Disorders

Hematologic Diseases

Hemorrhagic Disorders

Participants who meet the multiple myeloma diagnostic criteria of IMWG are eligible.

We will draw 2-5 mL of peripheral blood and utilize multiparameter flow cytometry to measure the level of circulating plasma cells.

Peripheral blood test

Chunyan Sun

This study aims to investigate the prognostic value of circulating plasma cells (CPCs) in patients with multiple myeloma and explore whether CPCs detection might be used in place of bone marrow aspiration for disease monitoring.

Circulating plasma cells (CPCs) represents a phenotypic subset of bone marrow multiple myeloma (MM) cells, which would contribute to the progression and dissemination of the tumor. High-sensitivity techniques such as multiparameter flow cytometry provide a tool for better detection of CPCs; however, a clear threshold has not been identified. The primary objective of the current study is to identify an optimal threshold for CPCs quantified by 8-color flow cytometry (with antibodies to CD38, CD138, CD45, CD56, CD19, CD117 and cytoplasmic kappa and lambda immunoglobulin light chains) and determine the specific relationship between CPCs level and the prognosis of MM. In addition, the evaluation of CPCs at multiple time points will be performed to explore whether CPCs detection might be used in place of bone marrow aspiration for disease monitoring.

The Prognostic Value of CPCs Quantified by Flow Cytometry in Patients With Multiple Myeloma: a Prospective, Multicenter Clinical Trial

The Prognostic Value of Circulating Plasma Cells Quantified by Multiparameter Flow Cytometry in Patients With Multiple Myeloma: a Prospective, Multicenter Clinical Trial

To evaluate if there is a correlation between high CPCs level and poor PFS.

To evaluate if there is a correlation between CPCs level and rates and depth of response (IMWG response criteria).

To evaluate if there is a correlation between high CPCs level and poor OS.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Personalised Disease Monitoring in Metastatic Breast Cancer	NCT04597580	Breast Cancer M... Estrogen Recept...		18 Years -	The Christie NHS Foundation Trust
Clonal Evolution in Follicular Lymphoma	NCT03190928	Follicular Lymp...		18 Years -	National Institutes of Health Clinical Center (CC)
Personalised Disease Monitoring in Metastatic Breast Cancer	NCT04597580	Breast Cancer M... Estrogen Recept...		18 Years -	The Christie NHS Foundation Trust
The Prognostic Value of CPCs Quantified by Flow Cytometry in Patients With Multiple Myeloma: a Prospective, Multicenter Clinical Trial	NCT06228794	Multiple Myelom...	Peripheral bloo...	18 Years - 80 Years	Wuhan Union Hospital, China

Spots Global Cancer Trial Database for disease monitoring