Neoplasms

All Conditions

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Central Nervous System Depressants

All Drugs and Chemicals

Anesthetics

Radiation. High dose rate prostate brachytherapy is delivered under anesthesia in 2 procedures, 1-2 weeks apart.

HDR brachytherapy is also accomplished as an out-patient.

Temporary implantation of radioactive material into the prostate in the form of a stepping source of Iridium 192 that travels through 16-18 needles or catheters strategically placed through the prostate.

High dose rate prostate brachytherapy

Juanita M Crook, MD

Juanita Crook, MD

Hamid Raziee, MD

Bibi Naghibi Torbati, MD

This is an observational single-center trial for patients with localized prostate cancer suitable for High Dose Rate (HDR) brachytherapy as monotherapy. This study takes a multi-omics approach to study the mechanism of action of HDR brachytherapy through metabolomics, immunological, transcriptomics, and spectroscopic profiling. The results of this study will clarify the optimal dose for HDR prostate brachytherapy by documenting the dose-response relationship seen in the changing tumor metabolites after HDR brachytherapy and investigate the immunogenicity of HDR brachytherapy.

High Dose Rate (HDR) prostate brachytherapy is an effective and highly conformal means of delivering curative radiation to the prostate. Because of the high dose rate, initial studies applied this treatment cautiously in multiple sessions or fractions but this has gradually been reduced from 54 Gy in 9 fractions to 42 Gy in 6, then 36 Gy in 3, then 27 Gy in 2 and finally to one single fraction of 19 Gy. Each change in fractionation was calculated to be equivalent to the previous, and remarkably, efficacy was maintained until the final stage when treatment was reduced to a single fraction. This resulted in a significant drop in cure rates from over 90% to approximately 65%. The investigators assume that the prior fractions served to sensitize the tumor to subsequent radiation; however, this remains an open question.

This observational single-center trial for localized prostate cancer suitable for brachytherapy as monotherapy takes a novel multi-omics approach to study the mechanism of action of High Dose Rate (HDR) brachytherapy through metabolomics, immunological, transcriptomics, and spectroscopic profiling. This is achieved through (1) measurement of changes in metabolites as determined by Raman spectroscopy, (2) analysis of circulating tumor DNA in peripheral blood plasma, (3) evaluation of the changes in immune response by single cell RNA (scRNA)-sequencing, and (4) evaluation of gut microbiome composition before and after treatment. Secondary endpoints of the study include PSA nadir, time to nadir, PSA at 4 years and patterns of failure.

The study will enroll 100 men with localized prostate cancer suitable for brachytherapy as monotherapy. HDR brachytherapy is given in 2 fractions, each one under anesthesia, making it possible to obtain biopsies painlessly at both baseline prior to any treatment, and 1-2 weeks later prior to the second half of treatment. The results of this study will clarify the dose-response relationship for HDR brachytherapy, help to define the optimal dose, clarify the metabolic response to HDR brachytherapy, and investigate the potential immunogenicity of HDR brachytherapy.

Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer

Multi-omic Approach to Study High Dose Rate (HDR) Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer

We will report the most important biomolecules altered by radiation (importance determined by the relative change of the score as a component of the Raman spectrum before and after radiation) and whether that observed change corelates with PSA outcome for each individual patient

Number of patients with a (transient) increase in circulating tumor DNA after a single fraction of high-dose rate prostate brachytherapy will be reported

single cell-RNA sequencing of immune cell populations before and after 13.5 Gray of radiation will be used for each individual patient and the number of patients with a change in gene expression (through activation or inactivation) will be reported

To determine microbial composition before brachytherapy and report for the individual patient whether diversity in composition is changed or skewed after treatment with high dose rate prostate brachytherapy. Second assessment is after completion of both fractions of radiation. Number of patients with alteration in microbial composition will be reported.

PSA recorded every 6 months to 5 years and then annually to 10 years

4-year PSA \< 0.2 ng/ml (indicative of cure)

Acute and long-term toxicity will be graded using the Common Terminology Criteria for Adverse Events (CTCAE V5) at each follow up time point

BC Cancer Foundation

University of British Columbia

Vancouver Prostate Centre

British Columbia Cancer Agency

Professor of Radiation Oncology

Blood and Lymph Conditions

Rare Diseases

Leukemia

Leukemia, Myeloid

Leukemia, Myeloid, Acute

Neoplasms by Histologic Type

Hematologic Diseases

Myeloid Leukemia

Acute Myeloid Leukemia

Acute Non Lymphoblastic Leukemia

Acute Graft Versus Host Disease

Anti-Infective Agents

Antineoplastic Agents

Cytarabine

Daunorubicin

Gemtuzumab

Antineoplastic Agents, Immunological

Immunotoxins

Immunoconjugates

Immunologic Factors

Induction:

Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7

Consolidation:

Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6

Allogeneic transplantation or Autologous transplantation according to MRD level

Maintenance with glasdegib 100 mg daily for one year or until toxicity/relapse

Induction:

Gemtuzumab 3 mg/m2 day 1,4,7 Daunorubicin 60 mg/m2 day 1-3 Cytosine arabinoside 200 mg/m2 day 1-7

Consolidation:

Gemtuzumab 3 mg/m2 day 1 Daunorubicin 50 mg/m2 day 4-6 Cytosine arabinoside 500 mg/m2 twice a day, day 1-6

Allogeneic transplantation or Autologous transplantation according to MRD level

clinical observation

After randomization patients in both arms will be randomized to maintenance with glasdegib vs clinical observation

Glasdegib

Both arms, before randomization, will receive induction and consolidation with Gemtuzumab ozogamicin, Daunorubicin and Cytarabine

Gemtuzumab Ozogamicin

Paola Fazi

Enrico Crea

Zallio

Attilio Olivieri

Piero Galieni

Storti

Carluccio

Curti

Andrea Camera

Michele Gottardi

Milena Mirabile

Maria Ciccone

Alfredo Molteni

Barbara Scappini

Vincenza Martini

Germana Beltrami

Cimino

Di Renzo

Renato Bassan

Roberto Cairoli

Fabio Ciceri

Elisabetta Todisco

Mario Luppi

Felicetto Ferrara

Fabrizio Pane

Daniela Cilloni

Catello Califano

Antonino Mulè

Maria Enza Mitra

Patrizia Zappasodi

Maria Paola Martelli

Giuseppe Visani

Prassede Salutari

Daniele Vallisa

Michela Rondoni

Alessia Tieghi

Anna Maria Mianulli

Laura Cudillo

Adriano Venditti

Agostino Tafuri

Patrizia Chiusolo

Andrea Mengarelli

Giuseppe Avvisati

Maurizio Martelli

Nicola Cascavilla

Claudio Fozza

Ernesta Audisio

Endri Mauro

Francesco Zaja

Anna Candoni

MRD driven study. Addition of gemtuzumab to conventional chemotherapy to reduce MRD of patients with favorable/intermediate-risk AML. Post-consolidation assessment of MRD. Role of a post-SCT maintenance with glasdegib.

Setting up a multicenter, MRD (Minimal Residual Disease)-driven study that relies on addition of gemtuzumab ozogamicin to conventional chemotherapy to reduce the pre-transplant levels of MRD of patients with favorable/intermediate-risk (according to ELN 2017) AML. Post-consolidation assessment of MRD will be exploited to establish the final risk assignment and to verify whether the delivery of a post remission therapy intensity (AuSCT, Autologous Stem Cell Transplant, vs ASCT, Allogeneic Stem Cell Transplant) of which is MRD-driven will improve the outcome in terms of anti-leukemic efficacy. Finally, the role of a post-SCT maintenance with glasdegib will be explored.

Gemtuzumab Chemotherapy MRD Levels; Glasdegib Post-transplant, Adult Untreated, de Novo, Fav Interm Risk AML

Phase 3 Study to Assess Gemtuzumab, in Combination With Standard Chemotherapy, on MRD Levels, and the Role of Glasdegib as a Post-transplant Maintenance, in Adult, 18-60 Years, With Previously Untreated de Novo Fav-interm Risk AML

Percentage of MRD negativity after consolidation in patients treated in induction and consolidation with GO

Disease Free Survival (DFS) in patients randomized to glasdegib maintenance or clinical observation

Gruppo Italiano Malattie EMatologiche dell'Adulto

Azacitidine

Decitabine

Antimetabolites

Enzyme Inhibitors

All enrolled patients received maintenance therapy consisting of azacitidine or decitabine.

All enrolled patients received maintenance therapy consisting of Azacitidine (75mg/m2, subcutaneous injection, days 1-7) or Decitabine (20mg/m2, intravenous infusion, days 1-5), every three months as a cycle, for a maintenance therapy of 4-8 cycles.

Hypomethylating agent, Azacitidine or Decitabine

Sheng-Li Xue, M.D.

HMA maintenance therapy is expected to benefit overall survival (OS) and relapse free survival (RFS) in AML patients with favorable risk.

Applying hypomethylating agents, azacitidine or decitabine as maintenance therapy in favorable-risk AML may prolong the remission duration and further improve their long-term survival.

Apply hypomethylating agent, azacitidine or decitabine as maintenance therapy.

Maintenance Therapy of Hypomethylating Agent (HMA) in Favorable Risk Acute Myeloid Leukemia (AML) Patients

Maintenance Therapy of Hypomethylating Agent (HMA) in Favorable Risk Acute Myeloid Leukemia (AML) Patients: A Single Arm, Multi Center Clinical Trial

It is measured from the date of entry into this trial to the date of hematologic relapse or death from any cause; subjects not known to have any of these events are censored on the date they were last examined.

It is measured from the date of entry into this trial to the date of death from any cause; subjects not known to have died at last follow-up are censored on the date they were last known to be alive.

CIR defined as from the time of recruitment to the study until the date of hematologic relapse.

The First Affiliated Hospital of Soochow University

Principal Investigator

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer	NCT06200974	Localized Prost...	High dose rate ...	18 Years -	British Columbia Cancer Agency
Multi-omic Approach to Study HDR Brachytherapy for Favorable Risk and Low Tier Intermediate Risk Prostate Cancer	NCT06200974	Localized Prost...	High dose rate ...	18 Years -	British Columbia Cancer Agency
Gemtuzumab Chemotherapy MRD Levels; Glasdegib Post-transplant, Adult Untreated, de Novo, Fav Interm Risk AML	NCT04168502	Acute Myeloid L...	Glasdegib Gemtuzumab Ozog...	18 Years - 60 Years	Gruppo Italiano Malattie EMatologiche dell'Adulto
Maintenance Therapy of Hypomethylating Agent (HMA) in Favorable Risk Acute Myeloid Leukemia (AML) Patients	NCT06379360	Acute Myeloid L...	Hypomethylating...	16 Years -	The First Affiliated Hospital of Soochow University

Spots Global Cancer Trial Database for favorable risk