NCT04644068

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
702

participants targeted

Target at P75+ for phase_1 ovarian-cancer

Timeline
13mo left

Started Nov 2020

Longer than P75 for phase_1 ovarian-cancer

Geographic Reach
14 countries

68 active sites

Status
active not recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress84%
Nov 2020May 2027

First Submitted

Initial submission to the registry

October 26, 2020

Completed
17 days until next milestone

Study Start

First participant enrolled

November 12, 2020

Completed
13 days until next milestone

First Posted

Study publicly available on registry

November 25, 2020

Completed
6.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

May 28, 2027

Expected
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

May 28, 2027

Last Updated

February 19, 2026

Status Verified

February 1, 2026

Enrollment Period

6.5 years

First QC Date

October 26, 2020

Last Update Submit

February 17, 2026

Conditions

Keywords

PARP inhibitorBreast CancerPancreatic CancerProstate CancerOvarian CancerAZD5305, T-DXd, Enhertu, Trastuzumab Deruxtecan, Dato-DXd, Datopotamab Deruxtecan, Camizestrant

Outcome Measures

Primary Outcomes (2)

  • 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 Outcomes (33)

  • Best percentage change in target lesion

    From Screening to confirmed progressive disease (approximately 1 year)

  • Objective Response Rate

    From Screening to confirmed progressive disease (approximately 1 year)

  • Duration of Response

    From Screening to confirmed progressive disease (approximately 1 year)

  • Progression Free Survival

    From Screening to confirmed progressive disease (approximately 1 year)

  • Time To Response

    From Screening to confirmed progressive disease (approximately 1 year)

  • +28 more secondary outcomes

Study Arms (6)

Module 1: AZD5305 Monotherapy

EXPERIMENTAL

AZD5305 Monotherapy

Drug: AZD5305

Module 2: AZD5305 + Paclitaxel

EXPERIMENTAL

AZD5305 + Paclitaxel

Drug: AZD5305Drug: Paclitaxel

Module 3: AZD5305 + Carboplatin with or without Paclitaxel

EXPERIMENTAL

AZD5305 + Carboplatin with or without Paclitaxel

Drug: AZD5305Drug: PaclitaxelDrug: Carboplatin

Module 4: AZD5305 + Trastuzumab Deruxtecan

EXPERIMENTAL

AZD5305 + T- DXd

Drug: AZD5305Drug: T- Dxd

Module 5 AZD5305 + Datopotamab Deruxtecan

EXPERIMENTAL

AZD5305 + Dato-DXd

Drug: AZD5305Drug: Dato-DXd

Module 6 AZD5305 + Camizestrant

EXPERIMENTAL

AZD5305 + Camizestrant

Drug: AZD5305Drug: Camizestrant

Interventions

Oral PARP inhibitor

Module 1: AZD5305 MonotherapyModule 2: AZD5305 + PaclitaxelModule 3: AZD5305 + Carboplatin with or without PaclitaxelModule 4: AZD5305 + Trastuzumab DeruxtecanModule 5 AZD5305 + Datopotamab DeruxtecanModule 6 AZD5305 + Camizestrant

IV Anti-microtubule agent

Module 2: AZD5305 + PaclitaxelModule 3: AZD5305 + Carboplatin with or without Paclitaxel

IV Platinum chemotherapeutic

Module 3: AZD5305 + Carboplatin with or without Paclitaxel
T- DxdDRUG

IV Antibody-drug conjugate

Module 4: AZD5305 + Trastuzumab Deruxtecan

IV Antibody-drug conjugate

Module 5 AZD5305 + Datopotamab Deruxtecan

Oral SERD Molecule

Module 6 AZD5305 + Camizestrant

Eligibility Criteria

Age18 Years - 130 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.
  • 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).

You may not qualify if:

  • 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.
  • 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:
  • +15 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (68)

Research Site

Boston, Massachusetts, 02114, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

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Research Site

New York, New York, 10021, United States

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Oklahoma City, Oklahoma, 73104, United States

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Houston, Texas, 77030, United States

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Heidelberg, 3084, Australia

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Melbourne, 3000, Australia

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Vancouver, British Columbia, V5Z 1K1, Canada

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Toronto, Ontario, M5G 2M9, Canada

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Montreal, Quebec, H2X 0A9, Canada

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Montreal, Quebec, H3T 1E2, Canada

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Beijing, 100142, China

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Changchun, 130021, China

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Changsha, 410013, China

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Chengdu, 610041, China

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Chongqing, 400030, China

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Guangzhou, 510060, China

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Harbin, 150081, China

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Jining, 272029, China

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Shandong, China

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Shanghai, 200025, China

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Shanghai, 200032, China

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Taiyuan, 030001, China

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Wuhan, 430079, China

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Xi'an, 710061, China

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Brno, 656 53, Czechia

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Prague, 15006, Czechia

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Budapest, 1062, Hungary

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Budapest, 1082, Hungary

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Budapest, 1122, Hungary

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Milan, 20132, Italy

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Milan, 20141, Italy

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Modena, 41125, Italy

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Naples, 80131, Italy

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Padua, 35128, Italy

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Roma, 00168, Italy

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Chūōku, 104-0045, Japan

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Kōtoku, 135-8550, Japan

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Bydgoszcz, 85-796, Poland

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Gdansk, 80-214, Poland

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Gdynia, 81-519, Poland

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Grzepnica, 72-003, Poland

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Lodz, 90-302, Poland

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Torun, 87-100, Poland

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Warsaw, 02-781, Poland

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Moscow, 111123, Russia

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Moscow, 115478, Russia

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Moscow, 117997, Russia

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Moscow, 143442, Russia

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Seoul, 03080, South Korea

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Seoul, 03722, South Korea

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Seoul, 05505, South Korea

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Seoul, 06351, South Korea

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Barcelona, 08035, Spain

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Madrid, 28040, Spain

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Madrid, 28041, Spain

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Madrid, 28050, Spain

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Málaga, 29010, Spain

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Pozuelo de Alarcón, 28223, Spain

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Seville, 41013, Spain

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Chernivtsі, 58013, Ukraine

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Ivano-Frankivsk, 76018, Ukraine

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Kyiv, 03022, Ukraine

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Research Site

Uzhhorod, 88000, Ukraine

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Cambridge, CB2 0QQ, United Kingdom

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Research Site

Manchester, M20 4BX, United Kingdom

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Research Site

Oxford, OX3 7LE, United Kingdom

Location

Research Site

Sutton, SM2 5PT, United Kingdom

Location

Related Publications (1)

  • 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.

Related Links

MeSH Terms

Conditions

Ovarian NeoplasmsBreast NeoplasmsPancreatic NeoplasmsProstatic NeoplasmsCarcinoma, Non-Small-Cell LungColorectal NeoplasmsUrinary Bladder NeoplasmsStomach NeoplasmsBiliary Tract NeoplasmsUterine Cervical NeoplasmsEndometrial Neoplasms

Interventions

AZD5305PaclitaxelCarboplatinAZD9833

Condition Hierarchy (Ancestors)

Endocrine Gland NeoplasmsNeoplasms by SiteNeoplasmsOvarian DiseasesAdnexal DiseasesGenital Diseases, FemaleFemale Urogenital DiseasesFemale Urogenital Diseases and Pregnancy ComplicationsUrogenital DiseasesGenital Neoplasms, FemaleUrogenital NeoplasmsGenital DiseasesEndocrine System DiseasesGonadal DisordersBreast DiseasesSkin DiseasesSkin and Connective Tissue DiseasesDigestive System NeoplasmsDigestive System DiseasesPancreatic DiseasesGenital Neoplasms, MaleGenital Diseases, MaleProstatic DiseasesMale Urogenital DiseasesCarcinoma, BronchogenicBronchial NeoplasmsLung NeoplasmsRespiratory Tract NeoplasmsThoracic NeoplasmsLung DiseasesRespiratory Tract DiseasesIntestinal NeoplasmsGastrointestinal NeoplasmsGastrointestinal DiseasesColonic DiseasesIntestinal DiseasesRectal DiseasesUrologic NeoplasmsUrinary Bladder DiseasesUrologic DiseasesStomach DiseasesBiliary Tract DiseasesUterine NeoplasmsUterine Cervical DiseasesUterine Diseases

Intervention Hierarchy (Ancestors)

TaxoidsCyclodecanesCycloparaffinsHydrocarbons, AlicyclicHydrocarbons, CyclicHydrocarbonsOrganic ChemicalsDiterpenesTerpenesCoordination Complexes

Study Officials

  • Timothy Yap

    M.D. Anderson Cancer Center

    PRINCIPAL INVESTIGATOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Model Details: 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.
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

October 26, 2020

First Posted

November 25, 2020

Study Start

November 12, 2020

Primary Completion (Estimated)

May 28, 2027

Study Completion (Estimated)

May 28, 2027

Last Updated

February 19, 2026

Record last verified: 2026-02

Locations