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

Symptoms and General Pathology

Rare Diseases

Recurrence

Glioma

Glioblastoma

Astrocytoma

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

Phase 0: AZD1390 administered orally daily for 3 days prior to resection

Phase 1b: AZD1390 administered daily for 5 days concurrently with standard of care radiation therapy

Phase 0 Navigator

Nader Sanai, MD

This is an open-label, single-center Phase 0/1b study that will enroll at least 17 participants with recurrent WHO Grade 4 Glioma requiring re-radiation and approximately 20 participants with newly-diagnosed WHO Grade 4 glioma (nGBM). The trial will be composed of a Phase 0 component (subdivided into Arms A- C), and an expansion Phase 1b. Patients with tumors demonstrating a positive PK response in the Phase 0 component of the study will graduate to an expansion phase that combines therapeutic dosing of AZD1390 plus standard-of-care fractionated radiotherapy (RT).

AZD1390 in Recurrent and Newly Diagnosed WHO Grade 4 Glioma Patients

A Phase 0/1b, Single Center, Clinical Trial With an Expansion Phase of AZD1390 Plus Fractionated Radiotherapy in Recurrent and Newly Diagnosed WHO Grade 4 Glioma Patients

For PK analysis, total and unbound AZD1390 concentration in Gd-enhancing and Gd-non-enhancing tumor tissue.

The rate of 6-month progression-free survival (PFS6) measured from time of surgery to date of recurrence or death, whichever occurs first, will be summarized.

Number of adverse events through study completion

Number of clinical laboratory abnormalities per CTCAE

Barrow Neurological Institute

Ivy Brain Tumor Center

AstraZeneca

Nader Sanai

Director of the Ivy Brain Tumor Center

Nervous System Diseases

Heart and Blood Diseases

Diseases and Abnormalities at or Before Birth

Nutritional and Metabolic Diseases

Immune System Diseases

Brain Neoplasms

Neoplasm Metastasis

Ataxia

Cerebellar Ataxia

Telangiectasis

Ataxia Telangiectasia

Central Nervous System Neoplasms

Nervous System Neoplasms

Brain Diseases

Central Nervous System Diseases

Arm A: 35 Gy of Intensity-modulated radiation therapy (IMRT) administered at daily fractions of 3.5 Gy over 10 fractions (2 weeks) Arm B: 30 Gy of whole brain radiation therapy (WBRT) or partial brain radiation therapy (PBRT) administered at daily fractions of 3 Gy over 10 fractions (2 weeks).

\*\*Arm B has now closed to recruitment\*\* Arm C: 60 Gy of intensity-modulated radiation therapy (IMRT) administered at daily fractions of 2 Gy over 30 fractions (6 weeks)

Radiation Therapy

AZD1390 Administered in 3 Cycles depending on arm:

Cycle 0 (arms A and C): 1 dose prior to Radiation Therapy. For optional food effect assessment in Arm A, 2 doses prior to RT under both fed and fasted conditions. \*Note: the optional food effect assessment is currently not open to recruitment\*.

Cycle 1 (all arms): Intermittent or continuous dosing during Radiation Therapy (except for first 2 cohorts of Arm A).

Cycle 2 (arms A and C): 2 weeks adjuvant treatment after Radiation Therapy.

AstraZeneca Clinical Study Information Center

Patrick Wen

Brandon Imber

Mariza Daras

Jan Drappatz

Deborah Forst

Anthony Chalmers

Rajesh Jena

Susan Short

This study will test an investigational drug called AZD1390 in combination with radiation therapy for the treatment of brain tumors. This is the first time AZD1390 is being given to patients. This study will test safety, tolerability and PK (how the drug is absorbed, distributed and eliminated) of ascending doses of AZD1390 in combination with distinct regimens of radiation therapy

This first time-in patients (FTIP), open-label, multicentre study of AZD1390 will be conducted in the United States and in the United Kingdom, and it consists of three treatment arms: Arm A, B, C. This Phase 1 study will assess safety and tolerability of AZD1390 in combination with radiation therapy (RT) in brain malignancies. The combination cohorts have been designed to assess escalating cumulative doses of AZD1390 in settings with 3 different radiation treatment regimens:

* Arm A: 35 Gy over 2 weeks with intensity-modulated radiation therapy (IMRT) in patients with recurrent Glioblastoma Multiforme (GBM)
* Arms B: 30 Gy over two weeks with whole brain radiation therapy (WBRT)/ partial brain radiation therapy (PBRT) in patients with brain metastases. \*\*Arm B has now closed to recruitment\*\*
* Arm C: 60 Gy over 6 weeks (IMRT) in patients with primary GBM Each arm provides standard of care RT for the disease setting indicated with the experimental agent being administered in dose escalating cohorts.

AZD1390 will be administered to patients in three different Arms (A, B and C), with each arm receiving standard of care radiation therapy (RT) for their disease setting.

In arms A and C, AZD1390 will be administered in three cycles: Cycle 0 (before RT), Cycle 1 (during RT) and Cycle 2 (after RT).

In arm B, AZD1390 will be administered in cycle 1 only (during RT). Within each arm, AZD1390 will be administered in dose escalating cohorts, first in an intermittent and then in a consecutive fashion, to achieve daily administration prior to RT.

\*\*Arm B has now closed to recruitment\*\*

For Arm A, there is an optional food effect assessment during cycle 0. \*Note: the optional food effect assessment is currently not open to recruitment\*

A Study to Assess the Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients With Brain Cancer

A Phase I, Multicentre Study to Assess the Safety, Tolerability, and Pharmacokinetics of Ascending Doses of AZD1390 in Combination With Radiation Therapy in Patients With Glioblastoma Multiforme and Brain Metastases From Solid Tumors.

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

DLTs will be used to calculate the maximum tolerated dose (MTD). The MTD of AZD1390 is the maximum dose at which \<=25% patients experience a DLT.

For each adverse event CTCAE grade and causality (related to AZD1390 or radiotherapy) will be collected.

Defined as the time from the first dose of AZD1390 until the occurrence of any of the following events:

1. Tumor progression or recurrence based on RANO criteria
2. Secondary malignancy
3. Change in tumor treatment due to increase clinical symptoms
4. Death due to any cause

The proportion of patients achieving a complete or partial tumor response (CR or PR) according to RANO criteria.

The proportion of patients achieving a complete or partial tumor response (CR or PR) according to RANO-BM criteria.

The proportion of patients achieving a complete or partial tumor response (CR or PR) according to RECIST 1.1 criteria.

Blood samples will be collected to assess plasma concentrations of AZD1390 at a series of timepoints to derive Cmax

Blood samples will be collected to assess plasma concentrations of AZD1390 at a series of timepoints to derive Tmax

Blood samples will be collected to assess plasma concentrations of AZD1390 at a series of timepoints to derive AUC

Urine samples will be collected to assess urine concentrations of AZD1390 at a series of timepoints to derive renal clearance

Defined as the time from the first dose of AZD1390 until death from any cause

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
AZD1390 in Recurrent and Newly Diagnosed WHO Grade 4 Glioma Patients	NCT05182905	Glioblastoma Glioma Glioblastoma Mu... Glioma, Maligna...	AZD1390	18 Years -	St. Joseph's Hospital and Medical Center, Phoenix
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 Study to Assess the Safety and Tolerability of AZD1390 Given With Radiation Therapy in Patients With Brain Cancer	NCT03423628	Recurrent Gliob... Primary Gliobla... Brain Neoplasms... Leptomeningeal ...	Radiation Thera... AZD1390	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

Spots Global Cancer Trial Database for azd1390

Every month we try and update this database with for azd1390 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 azd1390

Every month we try and update this database with for azd1390 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 azd1390 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.