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Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies
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.
Study details:
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.
Eligibility criteria
Researchers look for people who fit a certain description, called eligibility criteria. See if you qualify.
Inclusion criteria
Exclusion criteria
Eligibility
Age eligible for study : 18 and older
Healthy volunteers accepted : No
Gender eligible for study: All
Things to know
Study dates
Study start: 2020-11-12
Primary completion: 2027-03-03
Study completion finish: 2027-03-03
Study type
TREATMENT
Phase
PHASE1
PHASE2
Trial ID
NCT04644068
Intervention or treatment
DRUG: AZD5305
DRUG: Paclitaxel
DRUG: Carboplatin
DRUG: T- Dxd
DRUG: Dato-DXd
DRUG: Camizestrant
Conditions
- • Ovarian Cancer
- • Breast Cancer
- • Pancreatic Cancer
- • Prostate Cancer
- • Non-small Cell Lung Cancer
- • Colorectal Cancer
- • Bladder Cancer
- • Gastric Cancer
- • Cervical Cancer
- • Endometrial Cancer
- • Additional Indications Below for Module 4 and 5
- • Biliary Cancer
- • Small Cell Lung Cancer Only in Module 5
Find a site
Closest Location:
Research Site
Research sites nearby
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Research Site
Melbourne, Not Specified, Australia
Study Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Participant Group/Arm | Intervention/Treatment |
---|---|
EXPERIMENTAL: Module 1: AZD5305 Monotherapy
| DRUG: AZD5305
|
EXPERIMENTAL: Module 2: AZD5305 + Paclitaxel
| DRUG: AZD5305
|
EXPERIMENTAL: Module 3: AZD5305 + Carboplatin with or without Paclitaxel
| DRUG: AZD5305
|
EXPERIMENTAL: Module 4: AZD5305 + Trastuzumab Deruxtecan
| DRUG: AZD5305
|
EXPERIMENTAL: Module 5 AZD5305 + Datopotamab Deruxtecan
| DRUG: AZD5305
|
EXPERIMENTAL: Module 6 AZD5305 + Camizestrant
| DRUG: AZD5305
|
What is the study measuring?
Primary outcome
Primary Outcome Measure | Primary Outcome Description | Primary Outcome Time Frame |
---|---|---|
The number of subjects with adverse events/serious adverse events | 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 | From time of Informed Consent to 28 + 7 days post last dose ( modules 1,2,3,5 and 6). 40+7 days post last dose for Module 4. |
The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol. | 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. | From first dose of study treatment until the end of Cycle 1. |
Secondary outcome
Secondary Outcome Measure | Secondary Outcome Description | Secondary Outcome Time Frame |
---|---|---|
Best percentage change in target lesion | Change in target lesion size from baseline, as defined by RECIST 1.1. | From Screening to confirmed progressive disease (approximately 1 year) |
Objective Response Rate | Best response until progression, as defined by RECIST 1.1. | From Screening to confirmed progressive disease (approximately 1 year) |
Duration of Response | Time from first response to progression or death , as defined by RECIST 1.1. | From Screening to confirmed progressive disease (approximately 1 year) |
Progression Free Survival | Time from C1D1 to progression or death, as defined by RECIST 1.1. | From Screening to confirmed progressive disease (approximately 1 year) |
Time To Response | Time from C1D1 to complete or partial response, as defined by RECIST 1.1. | From Screening to confirmed progressive disease (approximately 1 year) |
Effects of AZD5305 on pH2AX (Ser139) PD biomarker | Measure change from baseline in pH2AX | From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days) |
CA125 response (ovarian cancer) | at least a 50% reduction in CA125 levels from a pre-treatment sample as defined by GCIG criteria. | From Screening to confirmed progressive disease (approximately 1 year) |
Module 1: Area Under Curve (AUC) | 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. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 1: Maximum plasma concentration of the drug (Cmax) | The concentration of AZD5305 in plasma will be determined (Cmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 1: The time taken to reach the maximum concentration (Tmax) | The concentration of AZD5305 in plasma will be determined (Tmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 1 and Module 5: Objective Response Rate (prostate cancer) | Best response until progression, as defined by RECIST 1.1 or PCWG3 (bone) | From Screening to confirmed progressive disease (approximately 1 year) |
Module 1: Radiographic progression free survival (prostate cancer) | Time from C1D1 to progression or death, as defined by RECIST 1.1 and PCWG3(bone). | From Screening to confirmed progressive disease (approximately 1 year) |
Module 1: Proportion of subjects with ≥ 50% PSA decrease (prostate cancer) | PSA from baseline to the lowest post-baseline PSA result, confirmed by a second consecutive PSA assessment | From Screening to confirmed progressive disease (approximately 1 year) |
Module 1 : To investigate the effect of a high-fat meal on the PK of AZD5305 | 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 | Cycle 0, Day 1 (C0D1), in either the "fasted" or "fed" state, followed by a single oral dose of AZD5305 in the other state for Cycle 1, Day 1 (C1D1) at least 72 hours later; 1 cycle is 28 days. |
Module 2: Area Under Curve (AUC) | 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. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 2: Maximum plasma concentration of the drug (Cmax) | The concentration of AZD5305 in plasma will be determined (Cmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 2: The time taken to reach the maximum concentration (Tmax) | The concentration of AZD5305 in plasma will be determined (Tmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 3: Area Under Curve (AUC) | 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. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 3: Maximum plasma concentration of the drug (Cmax) | The concentration of AZD5305 in plasma will be determined (Cmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 3: The time taken to reach the maximum concentration (Tmax) | The concentration of AZD5305 in plasma will be determined (Tmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 4 : Area Under Curve | 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. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 4: Maximum plasma concentration of the drug (Cmax) | The concentration of AZD5305 in plasma will be determined (Cmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 4: The time taken to reach the maximum concentration (Tmax) | The concentration of AZD5305 in plasma will be determined (Tmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 4: Anti-Drug Antibody (ADA) | To investigate the presence of ADAs for T-DXd | Samples will be collected within 1 hour before dose administration on Day 1 of Cycle 1, 2, and 4, then every 4 Cycles (each cycle is 21 days), EoT, and at safety follow-up (40 days after last dose) as per Schedule of Assessments |
Module 4: To assess the preliminary anti-tumour activity of AZD5305 as monotherapy and in combination with T-DXd. | Time from C1D1 to progression or death, as defined by RECIST v 1.1 summarised at the 6 month landmark (PFS6) | From screening to approximately 6 months |
Module 5: Area Under Curve | 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. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 5: Maximum plasma concentration of the drug (Cmax) | The concentration of AZD5305 in plasma will be determined (Cmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 5: The time taken to reach the maximum concentration (Tmax) | The concentration of AZD5305 in plasma will be determined (Tmax will be derived). | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 5: Anti-Drug Antibody (ADA) | Presence of ADAs for Dato-DXd | Whole blood samples for determination of ADA for Dato-DXd in plasma will be collected in patients receiving Dato-DXd per the schedule specified in the SoA : Day 1 of Cycle 1, 2, 4, and 8 (each cycle is 21 days) , EoT, and then 28 day follow up visit. |
Module 5: Premilinary anti tumour activity AZD5305 in combination with | 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). | From screening to confirmed progresive disease ( approximately 12 weeks) |
Module 6: To characterise the PK of AZD5305 and camizestrant following a single dose and at steady state after multiple dosing, when given in combination. | 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 | At predefined interval throughout the treatment (approximately 12 weeks) |
Module 6: To evaluate the effect of camizestrant on the PK 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 camizestrant. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
Module 6: To evaluate the effect of AZD5305 on the PK of 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. | At predefined intervals throughout the treatment period (approximately 12 weeks) |
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