Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Symptoms and General Pathology

Prostatic Neoplasms

Adenocarcinoma

Neoplastic Cells, Circulating

Carcinoma

Neoplasms, Glandular and Epithelial

Neoplasms by Histologic Type

Antineoplastic Agents

All Drugs and Chemicals

Docetaxel

Active CTC assessment: Patients will receive first line docetaxel until progression by CTC, and/or disease progression according to treating clinician or completion of 10 cycles. CTC results will be available to the treating clinician to guide decision-making. A progressing CTC count on Day 1 will require confirmation with a second CTC count performed on Day 15 (-/+ 5 days) of that cycle. If a patient is found to have two successive CTC determinations showing progression by CTCs, the clinician will receive a recommendation to discontinue docetaxel on the following cycle.

Patients will receive first line docetaxel until disease progression according to treating clinician or completion of 10 cycles. Patients and treating clinicians will not be disclosed to the results of CTC determinations.

CTC Counts used to guide treatment switch

Active CTC Assessment

Johann De Bono, MBChB FRCP MSc PhD

CTC-STOP is a multicentre prospective randomised controlled phase III trial for metastatic castration-resistant prostate cancer patients.

This study will determine if serial CTC counts can be used as early markers of progression to direct early discontinuation of docetaxel chemotherapy in patients with mCRPC without adversely impacting overall survival, when compared with standard approaches to guide treatment switch decisions.

Patients with metastatic castration-resistant prostate cancer will be randomised 1:1 to either control group (standard of care) or intervention group (CTC-guided treatment). All patients will commence first line chemotherapy with docetaxel three-weekly and will receive a minimum of 3 cycles of treatment before any recommendation to discontinue first-line docetaxel.

* Control Group (standard of care): patients will receive first line docetaxel until disease progression according to treating clinician or completion of 10 cycles. Patients and treating clinicians will not be disclosed to the results of CTC determinations.
* Intervention Group (CTC guided treatment): patients will receive first line docetaxel until progression by CTC, and/or disease progression according to treating clinician or completion of 10 cycles. CTC results will be available to the treating clinician to guide decision-making. A progressing CTC count on Day 1 will require confirmation with a second CTC count performed on Day 15 (-/+ 5 days) of that cycle. If a patient is found to have two successive CTC determinations showing progression by CTCs, the clinician will receive a recommendation to discontinue docetaxel on the following cycle.

The reasons of the treating clinician to discontinue docetaxel will be reported in both groups. Patients who discontinue first line docetaxel according to the criteria for each group will be switched to second line chemotherapy with cabazitaxel. After progression on cabazitaxel or completion of 10 cycles, patients will be followed up for survival every three months until end of study.

Patients with CTC count \>5 CTC/7.5 mL at screening will be randomised 1:1 to either the control group (standard of care) or intervention group (CTC guided treatment). All patients will commence first line chemotherapy with docetaxel 75mg/m2 three-weekly and will receive a minimum of 3 cycles of treatment before any recommendation to discontinue first-line docetaxel.

Utilising CTC Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer

Utilising Circulating Tumour Cell (CTC) Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer: CTC-STOP Trial

Patient perception and preferences on therapeutic switch decisions will be assessed by the Treatment Switch Questionnaire, purposely designed by the study team.

Post-trial treatment will be collected for all patients during follow-up.

OS is defined as the time from the date of randomisation to the date of death (due to any cause). Patients alive at end of follow-up will be censored at the last documented date of follow-up.

An initial non-inferiority analysis will be conducted followed by a superiority analysis if non-inferiority is demonstrated

Proportion of patients in the intervention group that undergo a chemotherapy switch from docetaxel to cabazitaxel guided by CTC results that fulfil the pre-specified criteria for progression.

To determine if the study of serial CTC counts will decrease the administration of cytotoxic chemotherapy, number of cycles of chemotherapy in both groups will be reported.

Incidence of treatment-emergent adverse events (safety and tolerability) will be assessed throughout the treatment period using the NCI CTCAE v4.0 and summarised in tabular format. Reported toxicities will be coded using MedDRA (current version)

validated questionnaire that assesses pain severity (four items) and pain interference (11 items). Pain severity is measured through patients' rating of their level of current pain, average pain, least pain in the last 24 hours and worst pain in the last 24 hours, using an 11-point numerical rating scale (NRS) ranging from 0 (no pain) to 10 (pain as bad as you can imagine). The 'Worst Pain' and 'Average Pain' items of the BPI-SF are often used in clinical trials to singly represent pain severity.

FACT-P is a relevant, worldwide Patient reported outcome measure tool used for assessing the health-related quality of life in men with prostate cancer. The FACT-P will be used in this study as part of a wider Quality of Life analysis to compare both arms.

EQ-5D is a self reported questionnaire measuring generic health status. EQ-5D will be used in this study as part of a wider Quality of Life analysis to compare both arms.

PFS will be measured from the date of randomisation to the date of death (due to any cause) or disease progression (As per PCWG2 criteria), whichever occurs first. Patients alive and progression-free at the last documented date of follow-up will be censored at that date.

rPFS will be measured from randomisation to the occurrence of one of the following:

1. Development of new nodal / soft tissue (inclusive of measurable soft tissue associated with lytic bone -metastases) lesions by CT as defined in RECIST 1.1 criteria, and/or
2. Progression of bone disease by PCWG2 bone scan criteria and/or,
3. Death of any cause

In case of progression by bone scan, the date of progression will be considered as the date of the first bone scan showing new lesions.

The time to the first SSRE will be defined will be measured from the date of randomisation to the date of any of the following:

1. First use of external-beam radiation therapy to relieve skeletal symptoms
2. New symptomatic pathologic vertebral or non-vertebral bone fractures
3. Spinal cord compression
4. Tumour-related orthopaedic surgical intervention

Patients alive and free of SSRE at the last documented date of follow-up will be censored at that date.

CTC progression will be based on serial CTC levels collected during the study. Time to CTC Progression will be defined as the time from randomisation to the time of first blood test showing progression by CTCs, defined by:

1. Failure to achieve a 30% decline from Screening CTC counts (baseline) AND a failure to achieve a conversion from unfavourable (≥ 5 cells/7.5 mL) to favourable (\< 5 cells/7.5 mL) count; or
2. Conversion from favourable to unfavourable CTC counts after a previous CTC response; or
3. A 30% increase in CTC count from nadir after a previous CTC response and an unfavourable CTC count (i.e. CTC ≥ 5 cells/7.5 mL).

An additional CTC count will be required to confirm progression. If confirmed, the date of the first CTC count meeting criteria for progression will be used as progression date.

Serial CTC levels collected during the study will be compared to evaluate the % CTC change from Screening (baseline). Change at any time point will be classified into response CTC (decline \>30%), stable CTC (change between -30% and 30%) and progressive CTC (increase \>30%).

The endpoint of interest for this study is the proportion of patients with a stable CTC count by 12-weeks (or earlier if treatment discontinued).

PSA values will be measured at regular timepoints in the study. At each time point where PSA is measured, % change from baseline PSA value will be measured, maximum PSA decline at any time and decline after 12 weeks on 1st and 2nd line chemotherapy will be reported.

CTC response is defined by:

1. A conversion from unfavourable (\>= 5 CTC/7.5 mL) to favourable (\< 5 CTC/7.5 mL) CTC counts OR
2. A 30% or more decrease in CTC counts from screening (baseline).

Pain response will be evaluated only in patients with a median BPI score of ≥2 and will be defined as a reduction of 2 points or more from baseline median BPI score without an increase in analgesic score maintained for 3 or more weeks.

Pain Progression Pain progression will be defined as an increase of at least two-points in the worst pain score over the mean baseline score (as defined by the baseline BPI), maintained for at least two consecutive measurements approximately 3-weeks apart.

A decision analytic model will be developed, modelling the CTC guided and comparator interventions. The model will analyse the most cost-effective strategy for the management of patients with progressive disease.

Prostate Cancer UK

University of Twente

Sanofi

Janssen, LP

Menarini Group

Institute of Cancer Research, United Kingdom

Digestive System Diseases

Rare Diseases

Stomach Neoplasms

Stomach Cancer

Patients operated on for curative purposes at the Bordeaux University Hospital for gastric adenocarcinoma of any type or stage and Collection of two venous blood tubes

Gastrectomy

Emilie BESSEDE, PharmD, PhD

Marine JAUVAIN, PharmD

Caroline Gronnier, MD, PhD

In this study, gastric tumours and adjacent healthy mucosa will be collected from gastric cancer patients operated on for curative purposes. From this material, presence and characterisation of intratumoral bacteria will be determined. Intratumoral microbiota composition will be compared with healthy adjacent tissue, and the intratumoral microbiota composition will also be compared between different tumor types. The different bacterial signatures that we will characterise may be used as biomarkers.

Gastric adenocarcinoma is mainly linked to Helicobacter pylori infection, and this bacterium is classified as a class 1 carcinogen by the WHO. However, infection with this bacterium alone is not sufficient for the development of gastric adenocarcinoma. It is now recognised that environmental factors such as the digestive microbiota influence carcinogenesis. Improved sequencing techniques have shown that some tumours contain intracellular bacteria and that these are specific to the origin of the tumour. A study describing the existence of intratumoral bacteria was carried out on 7 different tumour types excluding gastric cancer. Gastric adenocarcinoma is a cancer with a poor prognosis, treatment, based mainly on surgery combined with conventional chemotherapy, is not very effective with a 5-year survival rate of less than 20%. Except for Her2+ cases, there is no specific treatment. It is therefore now essential to develop targeted and effective treatments.

The objective of this project is to define whether intratumoral bacteria exist in gastric cancer.

To achieve this, tumours and adjacent healthy mucosa from patients with gastric cancer will be collected and analysed in INSERM U1312 laboratory. The biological material studying consists only of remnants of biopsies of gastric tumours and adjacent healthy tissues, which are not needed in the pathology laboratory, from patients who undergo gastrectomy as part of their cancer management Two blood tubes for the isolation of possible circulating tumour cells will also be collected. From these materials, the presence of intratumoral bacteria will be determined by immunohistochemistry targeting components of the bacterial wall, by RNAscope® targeting 16S ribosomal RNA (16S rRNA) and by real-time quantitative PCR targeting 16S rDNA. Characterisation of the intratumoral microbiota will be performed by sequencing 16S rDNA gene. The collected blood will be tested for the presence of CSCs and, if CSCs are detected, the microbiota will be tested and characterised using the same techniques described above.

The primary endpoint will be the evidence of an intratumoral microbiota and its taxonomic description.

Characterisation of the Intratumoral Microbiome in Gastric Adenocarcinoma: to a Personalised Medicine

Description of intratumoral microbiota in gastric adenocarcinoma, no statistical tests will be necessary.

Institut National de la Santé Et de la Recherche Médicale, France

University Hospital, Bordeaux

Skin and Connective Tissue Diseases

Breast Neoplasms

Breast Diseases

Skin Diseases

Neoplasm Metastasis

Neoplastic Processes

Trastuzumab

Antineoplastic Agents, Immunological

8 mg/kg of loading dose IV over 90 minutes for the first cycle, followed by 6 mg/kg IV over 60 minutes every 3 weeks for the 5 subsequent cycles.

trastuzumab

Michail Ignatiadis, MD

Martine Piccart, MD

Christos Sotiriou, MD

Jean-Yves Pierga, MD

Brigitte Rack, MD

This is a randomized phase II trial for patients with HER2 negative primary Breast Cancer (BC) who after completing (neo) adjuvant chemotherapy and surgery have detectable circulating tumour cells (CTC) in peripheral blood.

Eligible patients will be randomised in 1:1 ratio to either the trastuzumab arm or the observation arm.

This is a randomized phase II trial for patients with HER2 negative primary BC who after completing (neo) adjuvant chemotherapy and surgery have detectable CTC(s) in peripheral blood (see eligibility criteria for details). Eligible patients will be randomized in 1:1 ratio to either the trastuzumab arm or the observation arm. Patients randomized to the trastuzumab arm will receive a total of 6 intravenous (IV) administrations every 3 weeks (loading dose 8 mg/kg IV and 5 cycles at 6 mg/kg every 3 weeks). Patients randomized to observation arm shall be observed for 18 weeks. Left ventricular ejection fraction (LVEF) assessment (MUGA and/or ECHO) will be done at baseline for all patients to be randomized. The next LVEF assessments of weeks 9 and week 18 will be done only in patients randomized to trastuzumab arm. Patient registered but with CTC negative result will not be followed-up.

Efficacy Study of Herceptin to Treat HER2-negative CTC Breast Cancer

TRastuzumab in HER2-negative Early Breast Cancer as Adjuvant Treatment for Circulating Tumor Cells (CTC) ("TREAT CTC" Trial)

To compare circulating tumour cell (CTC)detection rate at week 18 between trastuzumab treatment arm and observational arm.

Recurrence Free Interval (RFI) (key secondary endpoint) between trastuzumab and observation

Invasive Disease Free Survival between trastuzumab and observation

Disease Free survival between trastuzumab and observation

Overall Survival between trastuzumab and observation

To evaluate in a clinical trial setting the feasibility, reliability, within patient reproducibility and variability of the assay for CTC(s)

To correlate CTC detection rate at baseline and/or week 18 with RFI, IDFS, DFS, OS

To assess safety, especially cardiac safety, of trastuzumab in women with HER2 negative primary tumors and CTC

Hoffmann-La Roche

Janssen Diagnostics, LLC

SUCCESS

UNICANCER

European Organisation for Research and Treatment of Cancer - EORTC

Blood samples will be taken before start of treatment, at month 1, month 3, month 4 and month 6.

Women with metastatic breast cancer, receiving first line treatment of any kind (chemotherapy, endocrine treatment or treatment with antibodies) will be included in this trial. In connection to treatment, blood samples for determination and enumeration of circulating tumour cells will be collected at different time points. Serum and plasma will be collected and stored for future analysis of RNA and DNA.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Utilising CTC Counts to Optimize Systemic Therapy of Metastatic Prostate Cancer	NCT03327662	Adenocarcinoma ...	Active CTC Asse...	18 Years -	Institute of Cancer Research, United Kingdom
Characterisation of the Intratumoral Microbiome in Gastric Adenocarcinoma: to a Personalised Medicine	NCT05800236	Gastric Adenoca...	Gastrectomy	18 Years -	University Hospital, Bordeaux
Characterisation of the Intratumoral Microbiome in Gastric Adenocarcinoma: to a Personalised Medicine	NCT05800236	Gastric Adenoca...	Gastrectomy	18 Years -	University Hospital, Bordeaux
Efficacy Study of Herceptin to Treat HER2-negative CTC Breast Cancer	NCT01548677	Breast Cancer Human Epidermal... Circulating Tum...	trastuzumab	18 Years -	European Organisation for Research and Treatment of Cancer - EORTC
Enumeration and Molecular Characterization of Circulating Tumour Cells in Women With Metastatic Breast Cancer	NCT01322893	Metastatic Brea...		18 Years -	Lund University Hospital
Enumeration and Molecular Characterization of Circulating Tumour Cells in Women With Metastatic Breast Cancer	NCT01322893	Metastatic Brea...		18 Years -	Lund University Hospital

Spots Global Cancer Trial Database for circulating tumour cells