Neoplasms

Respiratory Tract (Lung and Bronchial) Diseases

All Conditions

Lung Neoplasms

Carcinoma, Non-Small-Cell Lung

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Antineoplastic Agents

All Drugs and Chemicals

Durvalumab

Olaparib

Antineoplastic Agents, Immunological

Poly(ADP-ribose) Polymerase Inhibitors

Enzyme Inhibitors

This study arm will include up to 12 months of consolidation durvalumab for eligible participants following the completion of radiotherapy +/- DDRi.

Administered as 30 fractions of 2Gy. Total 60 60Gy. Administered once daily monday to friday.

Radiotherapy

Olaparib Oral Tablet [Lynparza]

AZD1390

Ceralasertib

AZD5305

Jamie B Oughton, MPhil

Jonathan McAleese

Huiqi Yang

Paul Shaw

Merina Ahmed

Stephen Harrow

Kevin Franks

Crispin Hiley

Corinne Faivre-Finn

Clara Chan

Alastair Greystoke

Adam Hassani

Matthew Hatton

Alastair Greystoke, MB ChB, MSc, PhD

Corinne Faivre-Finn, MD, PhD

CONCORDE is a multi-institution, multi-arm, Phase IB study that will determine the recommended phase II dose (RP2D) and safety profiles of different DNA damage repair inhibitors (DDRis) when given in an open label fashion in combination with fixed dose curative intent radiotherapy (RT) in patients with stage IIB/IIIA/IIIB NSCLC, followed by up to 12 months of consolidation durvalumab immunotherapy in selected study arms. The RP2D will be evaluated by incorporating the number of observed dose limiting toxicities (DLTs) into a time to event continuous reassessment method (TiTE- CRM) model within each of the experimental arms. TiTE-CRM is used here to take into account longer-term toxicities up to 13.5 months post start of radiotherapy and use these to inform dose escalation decision making.

Radiotherapy is an effective treatment for patients with non-small cell lung cancer (NSCLC) that has not spread beyond the chest area. Radiotherapy is used as a curative treatment but unfortunately for most patients the cancer can return. Radiotherapy kills cells by damaging their DNA. Cells have the ability to repair that damage, especially the cells of normal tissue. If DNA repair can be prevented radiotherapy should be more effective causing the cancer cells to die.

The study will use new drugs that affect how cells repair DNA damage, called DNA damage response inhibitors (DDRi). These will be given together with radiotherapy to hopefully improve the effectiveness of radiotherapy, followed by up to 12 months of durvalumab immunotherapy in selected study arms to develop the trial in line with the standard of care for NSCLC. The study will try to find out the most effective and safe dose of this combination treatment. This will be a clinical trial where patients due to have radiotherapy, with the hope of successful treatment that could lead to cure from their cancer or extension of life, will be offered entry onto the study. All patients will receive their radiotherapy, with 3 out of every 4 people also receiving a single DDRi drug alongside this. Both patients and study doctors will know prior to the start of the actual treatment whether a DDRi will be given, and if so which one; no placebos will be used. The patients will be followed closely to check for side effects and to assess how their cancer is responding to treatment. Blood samples will be taken to monitor treatment progress and to try to predict which patients are most likely to benefit from this type of combined treatment.

The trial is designed as a randomised Phase I dose escalation platform study, using the TiTE CRM design to find the RP2D of each DDRi with RT combination. At the time of patient identification the treating centre will be informed of the allocated study arm following a pre-specified prioritisation schedule. Consenting participants will be randomised between DDRi with RT or RT only. Patients are not randomised between experimental arms nor will endpoints be compared between experimental arms. RT only participants will be pooled across the platform to provide contemporary data on toxicity.

A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC

A Platform Study of DNA Damage Response Inhibitors in Combination With Conventional Radiotherapy in Non Small Cell Lung Cancer

De-identified individual participant data datasets generated and/or analysed during the current study will be available upon request from the Clinical Trials Research Unit, University of Leeds. Data will be made available at the end of the trial. Data will remain available from then on for as long as CTRU retains the data.

CTRU makes data available by a 'controlled access' approach. Data will only be released for legitimate secondary research purposes, where the Chief Investigator, Sponsor and CTRU agree that the proposed use has scientific value and will be carried out to a high standard (in terms of scientific rigour and information governance and security), and that there are resources available to satisfy the request. Data will only be released in line with participants' consent, all applicable laws relating to data protection and confidentiality, and any contractual obligations to which the CTRU is subject.

Dose-limiting toxicities (DLTs), within 13.5 months of starting radiotherapy, in order to establish the Recommended Phase II Dose (RP2D) of each DDRi-RT combination.

Safety will be reported based on the occurrence of SAEs, SARs and SUSARs. Toxicity will be reported based on adverse events, as graded by CTCAE V5.0, and determined by routine clinical assessments at each centre.

Treatment compliance will be measured by overall radiotherapy treatment time and delays, omissions and reductions to treatment doses (both DDRi and RT).

Best overall response will be measured as the best response (complete response, partial response or stable disease) recorded until disease progression, reported up to 2 years post-RT. This will be assessed using RECIST 1.1

This will be assessed using the Green Criteria. Disease Control includes either the complete disappearance of all evidence of malignant disease or residual radiographic abnormalities assessed by chest CT scan at 3 and 6 months after completion of RT, which then remains stable for an additional 6 months or more and which then qualifies as controlled local disease.

Participants who have not progressed at the time of analysis will be censored at the last date they were known to be alive and progression free

Participants who have not died at the time of analysis will be censored at the last date they were known to be alive

Health Related Quality of Life will be determined using EORTC QLQ-C30, IL-73 and IL-74

Objective response rate (ORR) is defined as the proportion of patients who have a partial or complete response to therapy. The proportion of patients with evaluable scans that achieve at least a partial response, as defined by RECIST v1.1(31), will be presented with 95% confidence intervals.

University of Manchester

Newcastle University

University of Oxford

The Leeds Teaching Hospitals NHS Trust

Beatson West of Scotland Cancer Centre

University of Glasgow

Velindre NHS Trust

University College London Hospitals

Queen's University, Belfast

University of Sheffield

University of Leeds

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Prostatic Neoplasms

Genital Neoplasms, Male

Urogenital Neoplasms

Genital Diseases

Genital Diseases, Male

Urogenital Diseases

Prostatic Diseases

Male Urogenital Diseases

Abiraterone Acetate

Hormones

Hormone Antagonists

Cytochrome P-450 Enzyme Inhibitors

Patients will receive an oral dose of AZD5305 and Enzalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Patients will receive an oral dose of AZD5305 and Abiraterone Acetate once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Patients will receive an oral dose of AZD5305 once daily and Darolutamide twice daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Patients will receive an oral dose of AZD5305 and Apalutamide once daily until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Patients will receive an oral dose of AZD5305 once daily

Patients will receive an oral dose of Enzalutamide once daily

Enzalutamide

Patients will receive an oral dose of Abiraterone Acetate once daily

Patients will receive an oral dose of Darolutamide twice daily

Darolutamide

Patients will receive an oral dose of Apalutamide once daily

Apalutamide

AstraZeneca Clinical Study Information Center

This study will evaluate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and preliminary efficacy of AZD5305 when given in combination with new hormonal agents (NHAs) in patients with Metastatic Prostate Cancer.

The study consists of 2 parts, Part A and Part B. Part A consists of the dose escalation cohorts and will include patients with metastatic castration resistant prostate cancer (mCRPC) or metastatic castration-sensitive prostate cancer (mCSPC); Part B consists of dose expansion cohorts and will include patients with mCSPC only.

Part A comprises 4 individual arms each evaluating the safety, tolerability, and preliminary efficacy of AZD5305 in combination with a specific new hormonal agent (NHA). Part B comprises up to 4 individual arms (arms to be opened at Sponsor's discretion) each investigating the preliminary efficacy and aims to further build on the safety data for the combination of AZD5305 with a specific NHA.

Approximately 783 patients will be enrolled and screened to ensure the required number of evaluable patients in each part and arm are enrolled. For Part A, 356 patients may be screened to obtain up to approximately 308 patients that can be assigned to study treatments across all study arms (1 to 4). For Part B dose expansion cohorts, up to 427 patients may be screened to obtain up to approximately 360 patients that can be assigned to study treatments across all study arms (1 to 4).

Study treatment administration will continue until disease progression, initiation of alternative anticancer therapy, unacceptable toxicity, withdrawal of consent, or other reasons to discontinue study treatment occur.

Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer

A Multi-arm, Open-label Phase I/IIa Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of AZD5305 in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer (PETRANHA)

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

Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline will be assessed.

To assess the safety and tolerability of AZD5305 when given in combination with NHA.

To characterise the PK (AUC) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.

To characterise the PK (Cmax) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.

To characterise the PK (tmax) of AZD5305 at steady state after multiple dosing of AZD5305 monotherapy.

To characterise the PK (AUC) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.

To characterise the PK (Cmax) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.

To characterise the PK (tmax) of AZD5305 following oral dose administration of AZD5305 in combination with NHA.

To assess the preliminary antitumour activity of AZD5305 in combination with NHA. ORR will be assessed as per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 (soft tissue) and Prostate Cancer Clinical Trials Working Group 3 (PCWG3) and is defined as the percentage of patients who have a confirmed visit response of complete response (CR) or partial response (PR) in their soft tissue disease and no disease progression in their bone scan.

To assess the preliminary antitumour activity of AZD5305 in combination with NHA. DoR is defined as the time from the date of first documented response (which is subsequently confirmed) until date of documented progression or death in the absence of progressive disease (PD).

To assess the preliminary antitumour activity of AZD5305 in combination with NHA. TTR is defined as the time from first dose until the first documentation of a subsequently confirmed objective response.

To assess the preliminary antitumour activity of AZD5305 in combination with NHA. rPFS is defined as the time from start of first treatment until progression as per RECIST v1.1 (soft tissue) and PCWG3 criteria (bone) or death from any cause.

To assess the preliminary antitumour activity of AZD5305 in combination with NHA. Percentage change in tumour size will be determined for patients with measurable disease at baseline.

To assess the preliminary antitumour activity of AZD5305 in combination with NHA.

To characterize the PK (AUC) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305

To characterize the PK (Cmax) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305

To characterize the PK (tmax) of Enzalutamide in plasma at steady state when given orally in combination with AZD5305

To characterize the PK (AUC) of Apalutamide in plasma at steady state when given orally in combination with AZD5305

To characterize the PK (Cmax) of Apalutamide in plasma at steady state when given orally in combination with AZD5305

To characterize the PK (tmax) of Apalutamide in plasma at steady state when given orally in combination with AZD5305

To investigate HRRm (including BRCA1/2) and their relationship with clinical response

Bayer

AstraZeneca

Skin and Connective Tissue Diseases

Digestive System Diseases

Gland and Hormone Related Diseases

Rare Diseases

Breast Neoplasms

Stomach Neoplasms

Small Cell Lung Carcinoma

Ovarian Neoplasms

Carcinoma, Ovarian Epithelial

Pancreatic Neoplasms

Urinary Bladder Neoplasms

Uterine Cervical Neoplasms

Endometrial Neoplasms

Gastrointestinal Neoplasms

Digestive System Neoplasms

Gastrointestinal Diseases

Endocrine Gland Neoplasms

Pancreatic Diseases

Endocrine System Diseases

Ovarian Diseases

Adnexal Diseases

Genital Diseases, Female

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Genital Neoplasms, Female

Gonadal Disorders

Uterine Neoplasms

Uterine Diseases

Stomach Cancer

Small Cell Lung Cancer

Ovarian Cancer

Ovarian Epithelial Cancer

Pancreatic Cancer

Biliary Tract Cancer

Antibodies

Paclitaxel

Carboplatin

Trastuzumab

Trastuzumab deruxtecan

Albumin-Bound Paclitaxel

Immunoglobulins

Tubulin Modulators

Antimitotic Agents

AZD5305 + Carboplatin with or without Paclitaxel

T- Dxd

Dato-DXd

Camizestrant

AZ Breast Cancer Study Navigators

Timothy Yap

This research is designed to determine if experimental treatment with PARP inhibitor, AZD5305, alone, or in combination with anti-cancer agents is safe, tolerable, and has anti-cancer activity in patients with advanced solid tumors.

This study is a Phase I/IIa modular, open-label, multi-center study of AZD5305 administered orally, either as monotherapy or in combination with other anti-cancer agents in patients with advanced solid malignancies.

The study consists of individual modules each evaluating the safety and tolerability of AZD5305 dosed as monotherapy, or with a specific combination partner:

* Module 1 (AZD5305 monotherapy)
* Module 2 (AZD5305 in combination with paclitaxel)
* Module 3 (AZD5305 in combination with carboplatin, with or without paclitaxel)
* Module 4 (AZD5305 in combination with T DXd)
* Module 5 (AZD5305 in combination with Dato-DXd).
* Module 6 (AZD5305 in combination with Camizestrant)

Modules 1 and 4 has 2 study parts: Part A consisting of dose-escalation cohorts and Part B, consisting of expansion cohorts. Modules 2, 3, 5 and 6 have only PART A.

Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

A Modular Phase I/IIa, Open-label, Multicentre Study to Assess the Safety, Tolerability, Pharmacokinetics, Pharmacodynamics and Preliminary Efficacy of Ascending Doses of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies

Number of patients with adverse events and with serious adverse events including abnormal clinical observations, abnormal ECG parameters, abnormal laboratory assessments and abnormal vital signs that changed from baseline

A DLT is defined as any toxicity that occurs from the first dose of study treatment (either AZD5305 or combination anti-cancer agent) up to and including the planned end of Cycle 1 (the DLT assessment period) that is assessed as unrelated to the disease or disease-related processes under investigation. DLTs occurring outside the DLT window (ie, late onset toxicities) may be defined as a DLT after consultation with the sponsor and investigators, based on the emerging safety profile.

Change in target lesion size from baseline, as defined by RECIST 1.1.

Best response until progression, as defined by RECIST 1.1.

Time from first response to progression or death , as defined by RECIST 1.1.

Time from C1D1 to progression or death, as defined by RECIST 1.1.

Time from C1D1 to complete or partial response, as defined by RECIST 1.1.

at least a 50% reduction in CA125 levels from a pre-treatment sample as defined by GCIG criteria.

The concentration of AZD5305 in plasma will be determined. Area under the curve is the integral of the concentration-time curve. The AUC reflects the actual body exposure to drug after administration. The AUC is dependent on the rate of elimination of the drug from the body and the dose administered.

The concentration of AZD5305 in plasma will be determined (Cmax will be derived).

The concentration of AZD5305 in plasma will be determined (Tmax will be derived).

Best response until progression, as defined by RECIST 1.1 or PCWG3 (bone)

Time from C1D1 to progression or death, as defined by RECIST 1.1 and PCWG3(bone).

PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment

Effect on High fat meal on PK parameters of AZD5305.PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without food

To investigate the presence of ADAs for T-DXd

Time from C1D1 to progression or death, as defined by RECIST v 1.1 summarised at the 6 month landmark (PFS6)

objective response rate and radiographic progression-free survival using RECIST v1.1.

Proportion of patients achieving a ≥ 50% decrease in PSA from baseline to the post-baseline PSA result, confirmed by a second consecutive PSA assessment at least 3 weeks later (PSA50 response).

Plasma concentrations and PK parameters of AZD5305 and camizestrant after single dose and multiple dose administration, including, but not limited to:

AUC, Cmax, Tmax, as data allow

PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without camizestrant.

PK parameters, including but not limited to AUC and/or AUC(0-t), Cmax, Tmax, AUC(0-t) and Cmax ratio, with and without AZD5305.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC	NCT04550104	Non Small Cell ...	Radiotherapy Olaparib Oral T... AZD1390 Ceralasertib AZD5305 Durvalumab	18 Years -	University of Leeds
A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC	NCT04550104	Non Small Cell ...	Radiotherapy Olaparib Oral T... AZD1390 Ceralasertib AZD5305 Durvalumab	18 Years -	University of Leeds
Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer	NCT05367440	Metastatic Pros...	AZD5305 Enzalutamide Abiraterone Ace... Darolutamide Apalutamide	18 Years - 130 Years	AstraZeneca
Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies	NCT04644068	Ovarian Cancer Breast Cancer Pancreatic Canc... Prostate Cancer Additional Indi... Non-small Cell ... Colorectal Canc... Bladder Cancer Gastric Cancer Biliary Cancer Cervical Cancer Endometrial Can... Small Cell Lung...	AZD5305 Paclitaxel Carboplatin T- Dxd Dato-DXd Camizestrant	18 Years - 130 Years	AstraZeneca
A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC	NCT04550104	Non Small Cell ...	Radiotherapy Olaparib Oral T... AZD1390 Ceralasertib AZD5305 Durvalumab	18 Years -	University of Leeds
Study of AZD5305 When Given in Combination With New Hormonal Agents in Patients With Metastatic Prostate Cancer	NCT05367440	Metastatic Pros...	AZD5305 Enzalutamide Abiraterone Ace... Darolutamide Apalutamide	18 Years - 130 Years	AstraZeneca
A Platform Study of Novel Agents in Combination With Radiotherapy in NSCLC	NCT04550104	Non Small Cell ...	Radiotherapy Olaparib Oral T... AZD1390 Ceralasertib AZD5305 Durvalumab	18 Years -	University of Leeds
Phase I/IIa Study for AZD5335 as Monotherapy and in Combination With Anti-cancer Agents in Participants With Solid Tumors	NCT05797168	Ovarian Cancer Lung Adenocarci...	AZD5335 AZD5305	18 Years - 130 Years	AstraZeneca

Spots Global Cancer Trial Database for azd5305

Every month we try and update this database with for azd5305 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for azd5305

Every month we try and update this database with for azd5305 cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for azd5305 cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.