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

Darolutimide 600mg BD + local consolidative radiotherapy, with a biological equivalent dose of 30Gy/10fx or greater if delivered with SABR. SABR is the preferred treatment approach, however conventional radiotherapy is acceptable. To up to 5 sites of disease

Darolutamide

Darolutamide + Consolidation Radiotherapy

Radiotherapy

Rebecca Montgomery

Jackie Buck

Lalith Ratnayake

Anthony Joshua

Libby Emmett

Mark Sidhom

Gurdip Hansra

Laurence Krieger

Sarah Gallagher

Yuvnik Trada

Jacqui Keller

Charles Lin

Narelle Wallace

Tanya Holt

David Pryor

Angela Byron

Ryan Appleton

Braden Higgs

Mary Polzella

Marketa Skala

Catherine Anderson

Mark Shaw

Lisa Selbie

Sarat Chander

Arun Azad

Cate Davey

Andrew See

Emily Floros

Tristan Molden-Hauer

Wilna Van Der Watt

Tee Lim

Enya Ong

Melvin Chua

Shankar Siva

Darolutamide is a drug that has a proven survival benefit in non-metastatic (M0) castrate resistant prostate cancer when using conventional imaging. However, it is estimated that \>90% of patients have disease apparent when using PSMA PET. This study investigates the use of local consolidation radiotherapy in this cohort of men.

This study explores the use of local consolidation therapy in the setting of Darolutamide in the initial diagnosis of metastatic castrate resistant prostate cancer (mCRPC). In the chemotherapy naïve mCRPC setting, the pattern of disease is of limited volume metastases (1-5) in 34%-40% of cases. As progression at known sites of macroscopic disease is the predominant cause of failure on systemic therapies, local consolidation therapy with stereotactic ablative body radiotherapy (SABR) may improve progression free survival (PFS) and overall survival (OS). This approach has been tested in the setting of lung cancer, in which consolidation SABR has resulted in OS benefit (HR of 0.40) in phase II studies. The novel approach of local consolidation therapy has not been tested as yet in mCRPC.

The secondary objective of this study proposal is to better understand the pattern of disease distribution at first diagnosis of CRPC. Previous studies have used conventional bone scan and CT imaging, and with these investigations the proportion of patients that are 'M0' is \~35%1. However, in the new era of PSMA PET, which is far more sensitive than conventional imaging, there exists a new group of men who are M0 on conventional imaging but are M1 on PSMA PET staging.

Thus, in the DECREASE study population, we expect the vast majority of patients with conventionally imaged 'M0 CRPC' will have disease detectable on PSMA PET scanning. In this context, the central hypothesis of this trial is that the addition of consolidation radiotherapy to darolutamide to PSMA detected sites of disease will improve the clinical outcome of patients compared to those patients receiving darolutamide alone.

Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA

Distribution of bone, nodal, visceral and recurrent primary disease on PSMA-PET/CT

Treatment related adverse events (CTCAE v 5.0)

PSMA avid disease at irradiated site / unirradiated site / bone / local / nodal / visceral

Bayer

Peter MacCallum Cancer Centre, Australia

Trans Tasman Radiation Oncology Group

Blood and Lymph Conditions

Immune System Diseases

Infections

Symptoms and General Pathology

Rare Diseases

Lymphoma

Acquired Immunodeficiency Syndrome

HIV Infections

HIV Seropositivity

Burkitt Lymphoma

Neoplasms by Histologic Type

Lymphoproliferative Disorders

Lymphatic Diseases

Immunoproliferative Disorders

Communicable Diseases

Epstein-Barr Virus Infections

Virus Diseases

Herpesviridae Infections

DNA Virus Infections

Tumor Virus Infections

Lymphoma, B-Cell

Lymphoma, Non-Hodgkin

Blood-Borne Infections

Sexually Transmitted Diseases

Sexually Transmitted Diseases, Viral

Lentivirus Infections

Retroviridae Infections

RNA Virus Infections

Syndrome

Immunologic Deficiency Syndromes

Lymphosarcoma

B-cell Lymphoma

Antineoplastic Agents

All Drugs and Chemicals

Anti-Infective Agents

Antirheumatic Agents

Dermatologic Agents

Reproductive Control Agents

Anti-Inflammatory Agents

Antiemetics

Neuroprotective Agents

Gastrointestinal Agents

Etoposide

Cytarabine

Cyclophosphamide

Doxorubicin

Liposomal doxorubicin

Methotrexate

Rituximab

Vincristine

Melphalan

Prednisolone

Immunomodulating Agents

Etoposide phosphate

Methylprednisolone

Methylprednisolone Acetate

Methylprednisolone Hemisuccinate

Prednisolone acetate

Prednisolone hemisuccinate

Prednisolone phosphate

Antimetabolites

Antiviral Agents

Immunosuppressive Agents

Immunologic Factors

Experimental treatment consists of an induction phase followed by a consolidation or intensified phase according to tumor response.

* dd -2 to 1: Methylprednisolone
* dd 0-1, Cyclophosphamide, associated on day 0 with Vincristine
* dd 2, Rituximab
* dd 7, Methotrexate
* dd 14, Rituximab
* dd 15, Etoposide
* dd 21, Methotrexate
* dd 29, Rituximab and Doxorubicin
* dd 36, Rituximab and VCR

At the end of this induction phase, subsequent treatment will be performed according to the objective response:

1. pts in CR: consolidation phase followed by bulky site irradiation
2. pts in PR: consolidation phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation
3. pts with SD after induction or PD during or after induction: intensification phase followed by BEAM conditioning regimen supported by ASCT and bulky irradiation

Induction Phase

* dd 1-2: cytarabine twice a day
* dd 3 and 11: rituximab
* dd 11-13: leukapheresis for PBPC collection.

Consolidation Phase (on day +50)

1. One or two courses of R-IVAC or R-ICE chemoimmunotherapy regimen, every three weeks as debulking.
2. CTX (dd 1) associated with rituximab on dd 3 and 10, followed by PBPC collection (dd 11-13);
3. AraC every 12 hours for four days (dd -5 to -2) supported by reinfusion of CD34+ cells (dd 0), rituximab infusion (dd -1 and +11) and second in-vivo purged PBPC collection (if needed).

Intensification phase

BCNU on dd 1; VP-16 every 12 hours on dd 2-5 and araC every 12 hours on dd 2-5; melphalan on dd 6, followed by the reinfusion of CD34+ cells

BEAM conditioning

At the end of the whole program, patients will be evaluated for involved-field irradiation with 6-10 MeV photons and a dose of 36 Gy (2 Gy/d, five fractions a week). Three subgroups of patients will be considered for radiotherapy

Consolidation radiotherapy

Andrés JM Ferreri, MD

This is a multicenter,open-label trial to evaluate activity and safety of the investigational intensive in HIV+ patients with Burkitt's lymphoma.

Experimental treatment consists of an induction phase followed by a consolidation or intensified phase according to tumor response.

Until recently, the immuno-compromised state of patients with concomitant HIV/AIDS and BL was thought to limit the ability to administer intensive chemotherapeutic regimens due to infection rate. However, the advent of highly active antiretroviral therapy (HAART) and evidence in diffuse large B-cell lymphomas that HIV-positive patients can tolerate standard chemotherapeutic regimens with improved outcomes have led investigators to treat HIV-positive patients with the same intensive chemotherapy regimens used to treat immuno-competent patients. Data suggest that these current approaches, along with supportive care, may result in improved patient outcomes, similar to those in the immuno-competent patient population.

The activity of feasibility of the proposed program will be assessed in HIV+ patients with Burkitt lymphoma with the aim to improve tolerability, minimize source consuming and supporting treatment and redu ce late sequels. Available combinations in this setting are really source demanding and toxic combinations showing high rates of septic complication and a treatment-related mortality of near 20%.

Short Term Intensified Chemo-immunotherapy in HIV-positive Patients With Burkitt Lymphoma

Phase II Study on Safety and Activity of a Short Term Intensified Chemo-immunotherapy Combination in HIV-positive Patients Affected by Burkitt Lymphoma

Objective lymphoma response achieved after the induction phase of the experimental treatment.

Assessment of incidence of grade 4 AE during experimental treatment (induction, consolidation and intensification phases as well as conditioning and autologous stem cell transplantation (if indicated)

Participants who will not achieve a complete or partial response after induction and consolidation phases will be referred to intensification phase, which will be followed by BEAM + ASCT. These patients will be assess for tolerabbility and AE during these therapeutic phases.

Participants will be assessed by conventional exams to define complete remission rate after the whole experiemntal program; that is after consolidation phase for patients who achieved complete remission after induction phase, after BEAM + ASCt for patients who achieved partial response after induction phase, and after intensification phase for patients who did not achieve an objective response after induction phase.

Andres J. M. Ferreri

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Darolutamide + Consolidation Radiotherapy in Advanced Prostate Cancer Detected by PSMA	NCT04319783	Advanced Prosta... Cancer of Prost... PSA Castrate Resist...	Darolutamide Radiotherapy	18 Years -	Trans Tasman Radiation Oncology Group
Short Term Intensified Chemo-immunotherapy in HIV-positive Patients With Burkitt Lymphoma	NCT01516593	HIV Burkitt's Lymph...	Induction Phase Consolidation P... Intensification... BEAM conditioni... Consolidation r...	18 Years - 60 Years	IRCCS San Raffaele
Short Term Intensified Chemo-immunotherapy in HIV-positive Patients With Burkitt Lymphoma	NCT01516593	HIV Burkitt's Lymph...	Induction Phase Consolidation P... Intensification... BEAM conditioni... Consolidation r...	18 Years - 60 Years	IRCCS San Raffaele

Spots Global Cancer Trial Database for consolidation radiotherapy