ACTIVE_NOT_RECRUITING

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

Conditions

Ovarian Cancer Breast Cancer Pancreatic Cancer Prostate Cancer Additional Indications Below for Module 4 and 5 Non-small Cell Lung Cancer Colorectal Cancer Bladder Cancer Gastric Cancer Biliary Cancer Cervical Cancer Endometrial Cancer Small Cell Lung Cancer Only in Module 5 PARP inhibitor AZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant

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Study Overview

This clinical trial focuses on testing the efficacy of different digital interventions to promote re-engagement in cancer-related long-term follow-up care for adolescent and young adult (AYA) survivors of childhood cancer.

Description

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.

Official Title

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

Quick Facts

Study Start:2020-11-12

Study Completion:2027-06-01

Study Type:Not specified

Phase:Not Applicable

Enrollment:Not specified

Status:ACTIVE_NOT_RECRUITING

Study ID

NCT04644068

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Ages Eligible for Study:18 Years to 130 Years

Sexes Eligible for Study:ALL

Accepts Healthy Volunteers:No

Standard Ages:ADULT, OLDER_ADULT

Inclusion Criteria	Exclusion Criteria
* Age ≥ 18 at the time of screening * Histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria.. * Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2) * Life expectancy ≥ 12 weeks * Progressive cancer at the time of study entry * Patients must have evaluable disease as defined in module-specific criteria for Part A and Part B * Adequate organ and marrow function as defined by the protocol. * For Part B expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific Module.	* Treatment with any of the following: 1. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment 2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study treatment 3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment 4. Any live virus or bacterial vaccine within 28 days of the first dose of study treatment * Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong inhibitors or inducers. * Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes. * Receiving continuous corticosteroids at a dose of \>10 mg prednisone/day or equivalent for any reason. * Major surgery within 4 weeks of the first dose of study treatment. * Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment. * Any history of persisting (\> 2 weeks) severe pancytopenia due to any cause * Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of \>10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment. Patients with leptomeningeal carcinomatosis are excluded. * patient with known predisposition to bleeding (e.g., active peptic ulceration, recent \[within 6 months\] haemorrhagic stroke, proliferative diabetic retinopathy). * Cardiac conditions as defined by the clinical study protocol * Other cardiovascular diseases as defined by any of the following: 1. Symptomatic heart failure, 2. uncontrolled hypertension, 3. hypertensive heart disease with significant left ventricular hypertrophy 4. acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months. 5. cardiomyopathy of any etiology 6. presence of clinically significant valvular heart disease 7. history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (\< 100 beats per minute) are permitted. 8. subjects with atrial fibrillation and optimally controlled ventricular rate are permitted 9. transient ischaemic attack, or stroke within 6 months prior to screening 10. patients with symptomatic hypotension at screening * Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML). * Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305 * Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).

Inclusion Criteria

Exclusion Criteria

* Age ≥ 18 at the time of screening
* Histological or cytological confirmation of advanced malignancy considered to be suitable for study treatment and meeting module specific eligibility criteria..
* Eastern Cooperative Oncology Group Performance status (ECOG PS: 0-2)
* Life expectancy ≥ 12 weeks
* Progressive cancer at the time of study entry
* Patients must have evaluable disease as defined in module-specific criteria for Part A and Part B
* Adequate organ and marrow function as defined by the protocol.
* For Part B expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour specimen is mandatory, where available, except if stated that it is optional in a specific Module.

* Treatment with any of the following:
1. Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
2. Any investigational agents or study drugs from a previous clinical study within 5 half-lives or 3 weeks (whichever is shorter) of the first dose of study treatment
3. Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
4. Any live virus or bacterial vaccine within 28 days of the first dose of study treatment
* Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4 (CYP3A4) strong inhibitors or inducers.
* Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes.
* Receiving continuous corticosteroids at a dose of \>10 mg prednisone/day or equivalent for any reason.
* Major surgery within 4 weeks of the first dose of study treatment.
* Radiotherapy with a wide field of radiation within 4 weeks or radiotherapy with a limited field of radiation for palliation within 2 weeks of the first dose of study treatment.
* Any history of persisting (\> 2 weeks) severe pancytopenia due to any cause
* Spinal cord compression or brain metastases unless asymptomatic, treated and stable and not requiring continuous corticosteroids at a dose of \>10mg prednisone/day or equivalent for at least 4 weeks prior to start of study treatment. Patients with leptomeningeal carcinomatosis are excluded.
* patient with known predisposition to bleeding (e.g., active peptic ulceration, recent \[within 6 months\] haemorrhagic stroke, proliferative diabetic retinopathy).
* Cardiac conditions as defined by the clinical study protocol
* Other cardiovascular diseases as defined by any of the following:
1. Symptomatic heart failure,
2. uncontrolled hypertension,
3. hypertensive heart disease with significant left ventricular hypertrophy
4. acute coronary syndrome (ACS)/acute myocardial infarction (AMI), unstable angina pectoris, coronary intervention procedure with percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG) within 6 months.
5. cardiomyopathy of any etiology
6. presence of clinically significant valvular heart disease
7. history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (\< 100 beats per minute) are permitted.
8. subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
9. transient ischaemic attack, or stroke within 6 months prior to screening
10. patients with symptomatic hypotension at screening
* Patients with myelodysplastic syndrome/acute myeloid leukaemia or with features suggestive of myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML).
* Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption of AZD5305
* Known allergy or hypersensitivity to investigational product(s) or any of the excipients of the investigational product(s).

Contacts and Locations

Principal Investigator

Timothy Yap

PRINCIPAL_INVESTIGATOR

M.D. Anderson Cancer Center

Study Locations (Sites)

Research Site

Boston, Massachusetts, 02114

United States

Research Site

Boston, Massachusetts, 02215

United States

Research Site

New York, New York, 10021

United States

Research Site

Oklahoma City, Oklahoma, 73104

United States

Research Site

Houston, Texas, 77030

United States

Collaborators and Investigators

Sponsor: AstraZeneca

Timothy Yap, PRINCIPAL_INVESTIGATOR, M.D. Anderson Cancer Center

Study Record Dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Registration Dates

Study Start Date2020-11-12

Study Completion Date2027-06-01

Study Record Updates

Study Start Date2020-11-12

Study Completion Date2027-06-01

Terms related to this study

Keywords Provided by Researchers

PARP inhibitor
Breast Cancer
Pancreatic Cancer
Prostate Cancer
Ovarian Cancer
AZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant

Additional Relevant MeSH Terms

Ovarian Cancer
Breast Cancer
Pancreatic Cancer
Prostate Cancer
Additional Indications Below for Module 4 and 5
Non-small Cell Lung Cancer
Colorectal Cancer
Bladder Cancer
Gastric Cancer
Biliary Cancer
Cervical Cancer
Endometrial Cancer
Small Cell Lung Cancer Only in Module 5