Ovarian CancerPhase 1/2PETRANCT04644068
Study of AZD5305 as Monotherapy and in Combination With Anti-cancer Agents in Patients With Advanced Solid Malignancies
A Phase 1/2 study testing AZD5305, Paclitaxel and Carboplatin in people with Ovarian Cancer and Breast Cancer, run by AstraZeneca at 68 sites in 14 countries.
Trial summary
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. Read more about this study
- Who is it for?
- Ages 18 to 130 years
- Conditions the study is for
- Ovarian Cancer, Breast Cancer, Pancreatic Cancer
- What is being tested?
- AZD5305, Paclitaxel and Carboplatin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 702 participants
- Where
- 68 sitesin 14 countries
- Study dates
- 12 Nov 2020to 28 May 2027
- Phase
- Phase 1/2
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 130 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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.
- For Part A:
- Patients may have received up to one prior line of therapy with a PARPi-based regimen (either as a treatment or as maintenance)
- For Part B:
- Patients must not have received prior therapy with a PARPi-based regimen (either as a treatment or as maintenance).
Who cannot join
- Treatment with any of the following:
- Nitrosourea or mitomycin C within 6 weeks of the first dose of study treatment
- 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
- Any other chemotherapy, immunotherapy or anticancer agents within 3 weeks of the first dose of study treatment
- 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.
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- 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:
- Symptomatic heart failure,
- uncontrolled hypertension,
- hypertensive heart disease with significant left ventricular hypertrophy
- 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.
- cardiomyopathy of any etiology
- presence of clinically significant valvular heart disease
- history of atrial or ventricular arrhythmia requiring treatment; subjects with atrial fibrillation and optimally controlled ventricular rate (< 100 beats per minute) are permitted.
- subjects with atrial fibrillation and optimally controlled ventricular rate are permitted
- transient ischaemic attack, or stroke within 6 months prior to screening
- 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).
- Prior malignancy whose natural history, in the Investigator's opinion, has the potential to interfere with safety and efficacy assessments of the investigational regimen.
- other module-specific criteria may apply
Trial locations and contacts
68 sites in 14 countries.
68 sites in 14 countries
China14 sites
Research Site
Beijing, 100142
Research Site
Changchun, 130021
Research Site
Changsha, 410013
Research Site
Chengdu, 610041
Research Site
Chongqing, 400030
Research Site
Guangzhou, 510060
Research Site
Harbin, 150081
Research Site
Jining, 272029
Research Site
Shandong
Research Site
Shanghai, 200025
Research Site
Shanghai, 200032
Research Site
Taiyuan, 030001
Research Site
Wuhan, 430079
Research Site
Xi'an, 710061
Poland7 sites
Research Site
Bydgoszcz, 85-796
Research Site
Gdansk, 80-214
Research Site
Gdynia, 81-519
Research Site
Grzepnica, 72-003
Research Site
Lodz, 90-302
Research Site
Torun, 87-100
Research Site
Warsaw, 02-781
Spain7 sites
Research Site
Barcelona, 08035
Research Site
Madrid, 28040
Research Site
Madrid, 28041
Research Site
Madrid, 28050
Research Site
Málaga, 29010
Research Site
Pozuelo de Alarcón, 28223
Research Site
Seville, 41013
Italy6 sites
Research Site
Milan, 20132
Research Site
Milan, 20141
Research Site
Modena, 41125
Research Site
Naples, 80131
Research Site
Padova, 35128
Research Site
Roma, 00168
United States5 sites
Research Site
Boston, Massachusetts, 02114
Research Site
Boston, Massachusetts, 02215
Research Site
Houston, Texas, 77030
Research Site
New York, New York, 10021
Research Site
Oklahoma City, Oklahoma, 73104
Canada4 sites
Research Site
Montreal, Quebec, H2X 0A9
Research Site
Montreal, Quebec, H3T 1E2
Research Site
Toronto, Ontario, M5G 2M9
Research Site
Vancouver, British Columbia, V5Z 1K1
Russia4 sites
Research Site
Moscow, 111123
Research Site
Moscow, 115478
Research Site
Moscow, 117997
Research Site
Moscow, 143442
South Korea4 sites
Research Site
Seoul, 03080
Research Site
Seoul, 03722
Research Site
Seoul, 05505
Research Site
Seoul, 06351
Ukraine4 sites
Research Site
Chernivtsі, 58013
Research Site
Ivano-Frankivsk, 76018
Research Site
Kyiv, 03022
Research Site
Uzhhorod, 88000
United Kingdom4 sites
Research Site
Cambridge, CB2 0QQ
Research Site
Manchester, M20 4BX
Research Site
Oxford, OX3 7LE
Research Site
Sutton, SM2 5PT
Hungary3 sites
Research Site
Budapest, 1062
Research Site
Budapest, 1082
Research Site
Budapest, 1122
Australia2 sites
Research Site
Heidelberg, 3084
Research Site
Melbourne, 3000
About this study
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
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.
Read the detailed description
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.
- Conditions
- Ovarian Cancer, Breast Cancer, Pancreatic Cancer, Prostate Cancer, Additional Indications Below for Module 4 and 5, Non-small Cell Lung Cancer
- Being tested
- AZD5305, Paclitaxel, Carboplatin, T- Dxd, Dato-DXd
- Keywords
- PARP inhibitor, Breast Cancer, Pancreatic Cancer, Prostate Cancer, Ovarian Cancer, AZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant
- Medical subject headings
- Ovarian Neoplasms, Breast Neoplasms, Pancreatic Neoplasms, Prostatic Neoplasms, Carcinoma, Non-Small-Cell Lung, Colorectal Neoplasms, Urinary Bladder Neoplasms, Stomach Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AZD5305Drug
Oral PARP inhibitor
PaclitaxelDrug
IV Anti-microtubule agent
CarboplatinDrug
IV Platinum chemotherapeutic
T- DxdDrug
IV Antibody-drug conjugate
Dato-DXdDrug
IV Antibody-drug conjugate
CamizestrantDrug
Oral SERD Molecule
| Study group | Role | What they receive |
|---|---|---|
| Module 1: AZD5305 Monotherapy | Experimental | AZD5305 Monotherapy Receives: Drug: AZD5305 |
| Module 2: AZD5305 + Paclitaxel | Experimental | AZD5305 + Paclitaxel Receives: Drug: AZD5305; Drug: Paclitaxel |
| Module 3: AZD5305 + Carboplatin with or without Paclitaxel | Experimental | AZD5305 + Carboplatin with or without Paclitaxel Receives: Drug: AZD5305; Drug: Paclitaxel; Drug: Carboplatin |
| Module 4: AZD5305 + Trastuzumab Deruxtecan | Experimental | AZD5305 + T- DXd Receives: Drug: AZD5305; Drug: T- Dxd |
| Module 5 AZD5305 + Datopotamab Deruxtecan | Experimental | AZD5305 + Dato-DXd Receives: Drug: AZD5305; Drug: Dato-DXd |
| Module 6 AZD5305 + Camizestrant | Experimental | AZD5305 + Camizestrant Receives: Drug: AZD5305; Drug: Camizestrant |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: 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.
Measured: From first dose of study treatment until the end of Cycle 1.
Secondary outcomes (33)
Best percentage change in target lesion
Change in target lesion size from baseline, as defined by RECIST 1.1.
Measured: From Screening to confirmed progressive disease (approximately 1 year)
Objective Response Rate
Best response until progression, as defined by RECIST 1.1.
Measured: 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.
Measured: 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.
Measured: 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.
Measured: From Screening to confirmed progressive disease (approximately 1 year)
Effects of AZD5305 on pH2AX (Ser139) PD biomarker
Measure change from baseline in pH2AX
Measured: 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.
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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)
Measured: 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).
Measured: 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
Measured: 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
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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.
Measured: 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).
Measured: 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).
Measured: 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
Measured: 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)
Measured: 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.
Measured: 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).
Measured: 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).
Measured: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: Anti-Drug Antibody (ADA)
Presence of ADAs for Dato-DXd
Measured: 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 Dato-DXd
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).
Measured: 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
Measured: 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.
Measured: 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.
Measured: At predefined intervals throughout the treatment period (approximately 12 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Nov 2020
- Study start12 Nov 2020
- Primary completion28 May 2027 (estimated)
- Study completion28 May 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Ovarian CancerStudies of the same condition, open and under way.
- More trials run by AstraZenecaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Model description
- 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.
- Masking
- None (open label)
- Enrolment
- 702 participants (actual)
Sponsor and investigators
- Lead sponsor
- AstraZeneca
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Timothy Yap, Principal investigator, M.D. Anderson Cancer Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04644068
- Sponsor's protocol ID
- D9720C00001
- Other IDs
- 2020-002688-77
- Acronym
- PETRA
- Status last verified
- Sep 2026
- First submitted
- 26 Oct 2020
- Last updated
- 21 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Illuzzi G, Staniszewska AD, Gill SJ, Pike A, McWilliams L, Critchlow SE, Cronin A, Fawell S, Hawthorne G, Jamal K, Johannes J, Leonard E, Macdonald R, Maglennon G, Nikkila J, O'Connor MJ, Smith A, Southgate H, Wilson J, Yates J, Cosulich S, Leo E. Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper. Clin Cancer Res. 2022 Nov 1;28(21):4724-4736. doi: 10.1158/1078-0432.CCR-22-0301.
PubMed 35929986
Study at a glance
From the registry record, last updated by the sponsor on 21 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT04644068
- Acronym / sponsor ID
- PETRA / D9720C00001
- Conditions
- Ovarian Cancer, Breast Cancer, Pancreatic Cancer, Prostate Cancer, Additional Indications Below for Module 4 and 5, Non-small Cell Lung Cancer
- Keywords
- PARP inhibitor, Breast Cancer, Pancreatic Cancer, Prostate Cancer, Ovarian Cancer, AZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Active, not recruiting
- Enrolment
- 702 participants (actual)
- Lead sponsor
- AstraZenecaIndustry (pharma, biotech, devices)
- Study start
- 12 Nov 2020 (actual)
- Primary completion
- 28 May 2027 (estimated)
- Study completion
- 28 May 2027 (estimated)
- First posted
- 25 Nov 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Detailed description
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Sequential
- Masking
- None (open label)
- Number of arms
- 6
- Model description
- 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.
| Arm | Type | Receives |
|---|---|---|
| Module 1: AZD5305 Monotherapy | Experimental | Drug: AZD5305AZD5305 Monotherapy |
| Module 2: AZD5305 + Paclitaxel | Experimental | Drug: AZD5305, Drug: PaclitaxelAZD5305 + Paclitaxel |
| Module 3: AZD5305 + Carboplatin with or without Paclitaxel | Experimental | Drug: AZD5305, Drug: Paclitaxel, Drug: CarboplatinAZD5305 + Carboplatin with or without Paclitaxel |
| Module 4: AZD5305 + Trastuzumab Deruxtecan | Experimental | Drug: AZD5305, Drug: T- DxdAZD5305 + T- DXd |
| Module 5 AZD5305 + Datopotamab Deruxtecan | Experimental | Drug: AZD5305, Drug: Dato-DXdAZD5305 + Dato-DXd |
| Module 6 AZD5305 + Camizestrant | Experimental | Drug: AZD5305, Drug: CamizestrantAZD5305 + Camizestrant |
Who may qualify
- Ages
- 18 to 130 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (30 listed)
- Treatment with any of the following:
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AZD5305Oral PARP inhibitor | Drug | Module 1: AZD5305 Monotherapy, Module 2: AZD5305 + Paclitaxel, Module 3: AZD5305 + Carboplatin with or without Paclitaxel, Module 4: AZD5305 + Trastuzumab Deruxtecan, Module 5 AZD5305 + Datopotamab Deruxtecan, Module 6 AZD5305 + Camizestrant |
| PaclitaxelIV Anti-microtubule agent | Drug | Module 2: AZD5305 + Paclitaxel, Module 3: AZD5305 + Carboplatin with or without Paclitaxel |
| CarboplatinIV Platinum chemotherapeutic | Drug | Module 3: AZD5305 + Carboplatin with or without Paclitaxel |
| T- DxdIV Antibody-drug conjugate | Drug | Module 4: AZD5305 + Trastuzumab Deruxtecan |
| Dato-DXdIV Antibody-drug conjugate | Drug | Module 5 AZD5305 + Datopotamab Deruxtecan |
| CamizestrantOral SERD Molecule | Drug | Module 6 AZD5305 + Camizestrant |
Primary outcome
The number of subjects with adverse events/serious adverse events
Time frame: 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.
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
The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol.
Time frame: From first dose of study treatment until the end of Cycle 1.
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.
33 secondary outcomes
Best percentage change in target lesion
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Objective Response Rate
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Duration of Response
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Progression Free Survival
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Time To Response
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Effects of AZD5305 on pH2AX (Ser139) PD biomarker
Time frame: From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days)
CA125 response (ovarian cancer)
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Module 1: Area Under Curve (AUC)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 1: Maximum plasma concentration of the drug (Cmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 1: The time taken to reach the maximum concentration (Tmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 1 and Module 5: Objective Response Rate (prostate cancer)
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Module 1: Radiographic progression free survival (prostate cancer)
Time frame: From Screening to confirmed progressive disease (approximately 1 year)
Module 1: Proportion of subjects with ≥ 50% PSA decrease (prostate cancer)
Time frame: 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
Time frame: 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)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2: Maximum plasma concentration of the drug (Cmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 2: The time taken to reach the maximum concentration (Tmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 3: Area Under Curve (AUC)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 3: Maximum plasma concentration of the drug (Cmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 3: The time taken to reach the maximum concentration (Tmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4 : Area Under Curve
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4: Maximum plasma concentration of the drug (Cmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4: The time taken to reach the maximum concentration (Tmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 4: Anti-Drug Antibody (ADA)
Time frame: 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 frame: From screening to approximately 6 months
Module 5: Area Under Curve
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: Maximum plasma concentration of the drug (Cmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: The time taken to reach the maximum concentration (Tmax)
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 5: Anti-Drug Antibody (ADA)
Time frame: 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 Dato-DXd
Time frame: 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.
Time frame: At predefined interval throughout the treatment (approximately 12 weeks)
Module 6: To evaluate the effect of camizestrant on the PK of AZD5305.
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Module 6: To evaluate the effect of AZD5305 on the PK of Camizestrant.
Time frame: At predefined intervals throughout the treatment period (approximately 12 weeks)
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Sep 2026.
- Derived from this study: PubMed 35929986Illuzzi G, Staniszewska AD, Gill SJ, Pike A, McWilliams L, Critchlow SE, Cronin A, Fawell S, Hawthorne G, Jamal K, Johannes J, Leonard E, Macdonald R, Maglennon G, Nikkila J, O'Connor MJ, Smith A, Southgate H, Wilson J, Yates J, Cosulich S, Leo E. Preclinical Characterization of AZD5305, A Next-Generation, Highly Selective PARP1 Inhibitor and Trapper. Clin Cancer Res. 2022 Nov 1;28(21):4724-4736. doi: 10.1158/1078-0432.CCR-22-0301.
- Breast Cancer Study Locator details (for US)Link provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Timothy Yap principal investigator
M.D. Anderson Cancer Center
68 sites in 14 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing AZD5305, Paclitaxel and Carboplatin in people with Ovarian Cancer and Breast Cancer, run by AstraZeneca at 68 sites in 14 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 30 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: under way, not looking for participants, as of the sponsor's last update on 21 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in China, Poland, Spain, Italy, United States and 9 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The number of subjects with adverse events/serious adverse events (time frame: 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 study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04644068, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Sep 2026.