Neoplasms

Urinary Tract, Sexual Organs, and Pregnancy Conditions

All Conditions

Skin and Connective Tissue Diseases

Prostatic Neoplasms

Leiomyoma

Breast Neoplasms

Myofibroma

Breast Diseases

Skin Diseases

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Neoplasms, Connective and Soft Tissue

Neoplasms by Histologic Type

Neoplasms, Connective Tissue

Connective Tissue Diseases

LFA102

Novartis Pharmaceuticals

The purpose of this first multi-dose study in cancer patients is to determine the maximum tolerated dose (MTD) or recommended phase II dose (RP2D), characterize the safety, tolerability and pharmacokinetics profile. Once the MTD has been established and/or a RP2D chosen, the study will enroll patients into the expansion portion of the study.

Phase I Study of LFA102 in Patients With Prolactin Receptor-positive Castration-resistant Prostate Cancer or Prolactin Receptor-positive Metastatic Breast Cancer

A Phase I, Multicenter, Open-label Study of LFA102 Administered Intravenously in Patients With Prolactin Receptor-positive Castration-resistant Prostate Cancer or Prolactin Receptor-positive Metastatic Breast Cancer

Symptoms and General Pathology

Adenocarcinoma

Disease Progression

Recruitment suspended and will not be re-opened. See intervention description below.

Recruitment complete. See intervention description below.

This part of the study will not be conducted following a review of data from Part A. See intervention description below.

Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Recruitment suspended and will not be re-opened.

Intermittent dosing of AZD5363

Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue to study withdrawal. Recruitment complete.

Intermittent dosing of AZD5363: oral solid formulation, twice daily (480 mg bid 4 days on and 3 days off). Treatment to begin on Day 1 and to continue until study drug withdrawal. This part of the study will not be conducted.

Paul Stockman, MBCHB, PHD

To investigate the safety, tolerability and anti-tumour activity of AZD5363, as monotherapy, in patients with metastatic Castrate-Resistant Prostate Cancer. AZD5363 will be investigated in patients who have progressed after chemotherapy (Part A) and in patients who have progressed before receiving chemotherapy (Part B).

Recruitment into Part A, Group 1 has been suspended. A new design for this group is currently being evaluated. Part A, group 2 patients (progressed after 1 or more 2nd generational anti-hormonal therapies) will receive AZD5363 480mg bid intermittently (4 days on/3days off).

Part B will only start if there is evidence of anti-tumour activity along with AZD5363 having an acceptable safety profile in Part A. Part B will be conducted in pre-chemotherapy patients on a dose and schedule selected from Part A.

A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity, Safety, Tolerability, and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC) (PYRUS)

Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.

A Phase Ib Multicentre Study of AZD5363 Monotherapy to Assess Anti-Tumour Activity,Safety,Tolerability,and Pharmacokinetics in Patients With Metastatic Castrate-Resistant Prostate Cancer (mCRPC)(PYRUS)

EORTC QLQ-C15-PAL, EORTC QLQ-PR25, and EORTC QLQ-BM22 Questionnaires

AstraZeneca

Abdominal Neoplasms

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Antineoplastic Agents

All Drugs and Chemicals

Amino Acids

Imatinib Mesylate

Tyrosine Kinase Inhibitors

Protein Kinase Inhibitors

Enzyme Inhibitors

Tyrosine

STI571 (Glivec®)

To investigate the ability of 600 mg of Glivec®, given once daily by mouth to patients with rising PSA following radical prostatectomy, to produce a sustained biochemical response during the first 6 months of treatment.

Glivec in Prostate Cancer Patients With Rising PSA Following Radical Prostectomy

An Open-label, Multicenter, Phase II Study to Evaluate the Ability of Glivec® (Imatinib, Formerly Known as STI571) to Produce a Biochemical Response in Patients With Rising PSA Following Radical Prostatectomy

Docetaxel

Tubulin Modulators

Antimitotic Agents

Participants receive capivasertib in combination with docetaxel and steroids on a background of ADT.

Participants receive placebo in combination with docetaxel and steroids on a background of ADT.

320 mg (2 tablets) BD given on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle.

Number of Cycles: until disease progression or unacceptable toxicity develops, death, or if the patient requests to stop the study treatment.

capivasertib

Patients will receive docetaxel in intravenous infusion, 75 mg/m2 BSA, on Day 1 of the 21-day cycles for up to 6 to 10 cycles, according to standard of care practices.

docetaxel

matched to capivasertib appearance (2 tablets) BD given orally on an intermittent weekly dosing schedule. Patients will be dosed on Days 2 to 5, 9 to 12, and 16 to 19 in each week of a 21-day treatment cycle. Number of Cycles: until disease progression or unacceptable toxicity develops, death, or if the patient requests to stop the study treatment.

placebo

AstraZeneca Clinical Study Information Center

This study will assess the efficacy and safety of capivasertib plus docetaxel versus placebo plus docetaxel in participants with metastatic castration resistant prostate cancer (mCRPC), all participants will receive the docetaxel with steroid therapy and receive androgen deprivation therapy. The intention of the study is to demonstrate that the combination of capivasertib plus docetaxel is superior to placebo plus docetaxel with respect to the overall survival of study participants, when overall survival is defined as the time from randomization until the date of death due to any cause.

Approximately 1000 participants will be enrolled and screened to achieve a total of approximately 790 assigned in a 1:1 ratio to one of the two parallel groups to receive either capivasertib or placebo, in combination with docetaxel on a background of ADT for the duration of the study.

The study is double-blinded, neither the patients nor the investigator will know what study intervention was assigned.

Capivasertib and placebo film-coated tablets will be identical in appearance and presented in the same packaging to ensure blinding of the capivasertib.

All personnel involved with the statistical analysis of the study will remain blinded until database lock and CSP deviations have been identified.

Study of Capivasertib + Docetaxel vs Placebo + Docetaxel as Treatment for Metastatic Castration Resistant Prostate Cancer (mCRPC)

A Phase III Double-Blind, Randomised, Placebo-Controlled Study Assessing the Efficacy and Safety of Capivasertib + Docetaxel Versus Placebo + Docetaxel as Treatment for Patients With Metastatic Castration Resistant Prostate Cancer (mCRPC)

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal.

All request will be evaluated as per the AZ disclosure commitment:

https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared.

Data will include clinical observations, ECG parameters, clinical chemistry / haematology / glucose metabolism parameters and vital signs assessed as the number of participants with adverse events.

Overall survival is defined as time from randomisation until the date of death due to any cause.

Radiographic Progression-free Survival (rPFS) is defined as time from randomization to radiographic progression as assessed by the investigator per Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1) for soft tissue and/or Prostate Cancer Working Group 3 (PCWG3) for bone or death due to any cause

Time to pain progression (TTPP) based on a 2-point increase from baseline in the Brief Pain Inventory-Short Form (BPI-SF) Item 3 'pain at its worse in the last 24 hours' score (scale from 0 \["no pain"\] to 10 \["pain as bad as you can imagine"\]) and/or initiation of/increase in opioid analgesic use.

SSRE is defined as time from randomisation until any of the following: use of radiation therapy to prevent or relieve skeletal symptoms; Occurrence of new symptomatic pathological bone fractures; Occurrence of spinal cord compression; Orthopaedic surgical intervention for bone metastasis

Time to deterioration in urinary symptoms (TTDUS) is defined as time from randomization until the change from baseline reaches a clinically meaningful deterioration threshold using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Prostate Questionnaire Urinary Symptoms (QLQ-PR25 (US)) subscale score (EORTC IL166), where the question responses are provided on a numerical rating scale ranging from 1 ("not at all") to 4 ("very much").

Time to deterioration in Physical Functioning (TTDPF) is defined as the time from randomization until the change from baseline reaches a clinically meaningful deterioration threshold using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Physical Functioning (QLQ-C30 PF) subscale score (EORTC IL166), where the question responses are provided on a numerical rating scale ranging from 1 ("not at all") to 4 ("very much").

Change from baseline in Brief Pain Inventory-Short Form (BPI-SF) pain at its worse in the last 24 hours score (scale from 0 \["no pain"\] to 10 \["pain as bad as you can imagine"\]), pain severity (the mean of the four pain severity items each of which ranges from 0 \["no pain"\] to 10 \["pain as bad as you can imagine"\]) and interference domain scores (the mean of the seven pain interference items each of which ranges from 0 \["does not interfere"\] to 10 \["completely interferes"\]).

Androgens

Hormones

Hormone Antagonists

Conventionally fractionated CRT (IMRT or Rapid Arc) to the TD of 50 Gy, 2.0 Gy d fx, 5 days a week over the period of 5 weeks AND two 10 Gy fractions of real- time HDR brachytherapy OR CRT combined with two stereotactic body radiotherapy boosts of 10 Gy per fraction delivered with dynamic SBRT technique (IMRT or Rapid Arc).

The choice between two ways of delivering radiation dose to the boost volume will be based solely on clinical criteria, decision made by interdisciplinary team, according to the institutional protocol (in non-randomized fashion).

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

Conventionally fractionated external beam conformal radiotherapy (IMRT or Rapid Arc) to the prostate and seminal vesicles (intermediate risk group) or to the prostate, SV and pelvic lymph nodes (high risk group) to the total dose of 50 Gy in 2.0 Gy per fraction, 5 days a week over the period of 5 weeks, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

CF-CRT to the prostate and SV (IM risk group) or to the prostate, SV and LN (high risk group) to the TD of 50 Gy, 2.0 Gy d fx, 5 days a week over the period of 5 weeks AND A. Two 10 Gy fractions of HDR BT 1-7 d. before external beam radiotherapy and one 1-7 d. after external beam radiotherapy OR B. Two stereotactic body radiotherapy (SBRT) fractions of 10 Gy to the prostate (CTV boost) delivered with dynamic SBRT technique (IMRT or Rapid Arc). First and second fraction of SBRT boost is scheduled 1-7 d. before and 1-7 d. after the start of conventionally fractionated radiotherapy, respectively.

CF-CRT combined with BT or SBRT boost.

Conventionally fractionated EB-CRT (IMRT or Rapid Arc) to the TD of 50 Gy, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).of 50 Gy in 2.0 Gy per fraction, 5 days a week over the period of 5 weeks, followed by a boost to the prostate (26 or 28 Gy in 2.0 Gy per fraction 5 days a week over the period of 2.5 weeks) to the total dose of 76 or 78 Gy (intermediate or high risk group of patients, respectively).

CF-CRT alone

Hormonal treatment: three months of neoadjuvant androgen deprivation (MAB -maximal androgen blockade) in all patients. Long-term (3 years) of adjuvant hormonotherapy (LHRH agonists only) in high risk patients.

Hormonal treatment (neoadjuvant androgen deprivation)

Katarzyna Behrendt, MD

Rafał Suwiński, MD, PhD

The purpose of this study is to compare the outcomes of conventionally fractionated conformal radiotherapy with CF-CRT combined with either high-dose-rate brachytherapy or stereotactic body radiotherapy for intermediate or high-risk prostate cancer patients.

Prostate cancer is considered as a disease with relatively slow natural course and good clinical prognosis. Such description, however, does not well refer to intermediate and high-risk cases where long-term rate of biochemical progression remains not satisfactory, and the available treatment modalities entail a considerable morbidity. Over the last decade several competitive therapeutic approaches have evolved in curative treatment for intermediate and high-risk prostate cancer. The use of intensity-modulated radiation therapy (IMRT) made possible to escalate the total dose to the prostate without excessive toxicity.

Based on assumption of low value of low α/β value for adenocarcinoma of prostate, there is a potential of escalating the biological dose to the tumor with higher dose per fraction. High-dose-rate brachytherapy (HDR-BT) is one of the options, with the ability to conform radiation dose to the prostate with sharp dose gradient adjacent to critical organs. An increasing number of studies suggest its usefulness as a boost in intermediate and high risk disease. The randomized trial conducted in UK compared external beam radiotherapy (EBRT) alone with EBRT and HDR brachytherapy as a boost. Combining EBRT with HDR BT - boost resulted in significantly higher relapse-free-survival (RFS) with comparable incidence of severe late toxicity. However, the total dose used in EBRT alone - arm and radiotherapy technique may be considered suboptimal according to current standards.

Stereotactic body radiotherapy (SBRT) may be an interesting alternative to HDR brachytherapy, not requiring implantation of multiple catheters and anesthesia. SBRT boost for advanced localized prostate cancer has the potential to reduce toxicity while escalating the dose. First results of trials combining conventional irradiation with hypofractionated stereotactic boost and institutional pilot results gave promising outcome.

The comparison of these modalities of radiation therapy for prostate cancer will be performed in the current phase III trial study.

Conformal Radiotherapy (CRT) Alone Versus CRT Combined With HDR BT or Stereotactic Body Radiotherapy for Prostate Cancer

Phase III Clinical Trial on Conventionally Fractionated Conformal Radiotherapy (CF-CRT) Versus CF-CRT Combined With High-dose-rate Brachytherapy or Stereotactic Body Radiotherapy for Intermediate and High-risk Prostate Cancer.

according to Phoenix definition (rise of PSA level of 2 ng/ml over the absolute nadir)

Maria Sklodowska-Curie National Research Institute of Oncology

Male individuals with elevated PSA and a positive MRI-driven biopsy AND male individuals with diagnosed prostate cancer (but prior to any treatment)

Male individuals with elevated PSA and a negative MRI-driven biopsy

Whole blood will be collected and processed within 2 hours. Samples will be brought to Hackensack University Medical Center and will be centrifuged.

The plasma samples will be tested for presence of prostasomes using the ExoPLA (Exosome in situ Proximity Ligation Assay) assay and the prostasomes will be purified for further miRNA sequencing.

Genetic analysis for the detection of prostasomes

Prostate cancer is the most frequently diagnosed cancer among men over 50 years old in Western societies, with an incidence that is steadily increasing in most countries. The current, most commonly used biomarker for prostate cancer is prostate specific antigen (PSA), which has well known limitations in accuracy and requires additional testing. However, prostate cancer cells secrete exosomes, also known as prostasomes, which are only detectable in the blood of prostate cancer patients. The presence of prostasomes in the blood is in itself a prostate cancer diagnosis. However, the assay that has been designed for the purification of prostasomes requires additional testing for evaluating its robustness and usefulness in the clinical setting. Additionally, the evaluation of the cargo of the purified prostasomes may provide more information on the nature of the prostate cancer, which may help develop a molecular assay for a prostate cancer liquid biopsy rather than a tissue biopsy. Therefore, the purpose of this study is two-fold: a validation phase where the purification of prostasomes will be tested on plasma collected from prostate cancer patients and a molecular testing phase where the contents of the purified prostasomes will be evaluated on their ability to determine the grade of the prostate tumors.

We will collaborate with Dr. Masood Kamali-Moghaddam at the Uppsala University (Department of Immunology, Genetics and Pathology) for molecular assay processing.

Prostasomes as Diagnostic Tool for Prostate Cancer Detection

Quantification and Purification of Circulating Prostasomes as Diagnostic Tool for Prostate Cancer Detection

true positive rate of the prostasomes purification methodology using the prostasome detection results for each of the patient specimens (cases and controls)

true negative rate of the prostasomes purification methodology using the prostasome detection results for each of the patient specimens (cases and controls)

identify the top 20 most frequently expressed miRNA markers and their level of expression in each of the case patient specimens

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Phase I Study of LFA102 in Patients With Prolactin Receptor-positive Castration-resistant Prostate Cancer or Prolactin Receptor-positive Metastatic Breast Cancer	NCT01338831	Castration-resi... Metastatic Brea... Uterine Leiomyo...	LFA102	18 Years -	Novartis
Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.	NCT01692262	Metastatic Cast... Efficacy, Safety and Tole... Pharmacokinetic... Pharmacodynamic... Tumour Response...	Intermittent do... Intermittent do... Intermittent do...	18 Years -	AstraZeneca
Glivec in Prostate Cancer Patients With Rising PSA Following Radical Prostectomy	NCT01316458	Prostatic Neopl... Genital Neoplas... Neoplasms, Abdo... Urogenital Neop... Genital Disease... Prostatic Disea... Antineoplastic ... Imatinib	STI571 (Glivec®...	18 Years -	Novartis
Study of Capivasertib + Docetaxel vs Placebo + Docetaxel as Treatment for Metastatic Castration Resistant Prostate Cancer (mCRPC)	NCT05348577	Prostate Cancer	capivasertib docetaxel placebo docetaxel	18 Years - 130 Years	AstraZeneca
Conformal Radiotherapy (CRT) Alone Versus CRT Combined With HDR BT or Stereotactic Body Radiotherapy for Prostate Cancer	NCT01839994	Prostate Cancer	CF-CRT combined... CF-CRT alone Hormonal treatm...	18 Years - 80 Years	Maria Sklodowska-Curie National Research Institute of Oncology
Conformal Radiotherapy (CRT) Alone Versus CRT Combined With HDR BT or Stereotactic Body Radiotherapy for Prostate Cancer	NCT01839994	Prostate Cancer	CF-CRT combined... CF-CRT alone Hormonal treatm...	18 Years - 80 Years	Maria Sklodowska-Curie National Research Institute of Oncology
Glivec in Prostate Cancer Patients With Rising PSA Following Radical Prostectomy	NCT01316458	Prostatic Neopl... Genital Neoplas... Neoplasms, Abdo... Urogenital Neop... Genital Disease... Prostatic Disea... Antineoplastic ... Imatinib	STI571 (Glivec®...	18 Years -	Novartis
Prostasomes as Diagnostic Tool for Prostate Cancer Detection	NCT03694483	Prostate Cancer	Genetic analysi...	18 Years -	Hackensack Meridian Health
Investigating Safety, Tolerability and Efficacy of AZD5363 in Prostate Cancer.	NCT01692262	Metastatic Cast... Efficacy, Safety and Tole... Pharmacokinetic... Pharmacodynamic... Tumour Response...	Intermittent do... Intermittent do... Intermittent do...	18 Years -	AstraZeneca

Spots Global Cancer Trial Database for prostate cancer,