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

Study Identifier:
D9720C00001
CT.gov Identifier:
NCT04644068
EudraCT Identifier:
2020-002688-77
EU Trial (CTIS) Number:
2022-502856-29-00
Study Contact Information:
N/A
Recruitment Complete

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Study Summary

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.

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.

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 and paclitaxel) Each Module has 2 study parts: Part A consisting of dose-escalation cohorts and Part B, consisting of expansion cohorts.

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

To assess the safety and tolerability of AZD5305 as monotherapy and in combination with anti-cancer agents in patients with advanced malignancies.

Medical Condition
The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.
  • Ovarian
  • Breast Cancers
  • Pancreas
  • Prostate
  • Non-Small Cell Lung Cancer
  • Bowel (Colorectal)
  • Bladder
  • Gastric
  • Bile Duct
  • Cervical cancer
  • Endometrial
  • Small Cell Lung
    • Phase
    The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
    I/II
    Sex
    Female & Male
    Age
    18 - 130 Years
    Study Drug
  • Drug: Experimental: Module 1: AZD5305 Monotherapy
    • Read More
  • Drug: Experimental: Module 3: AZD5305 + Carboplatin with or without Paclitaxel
  • Drug: Patients received AZD5305 QD PO until disease progression.
  • Drug: AZD5305 5 mg oral
  • Drug: Chinese common name: AZD5305
  • Drug: Dose escalation evaluated saruparib (10-140 mg QD; Part A) with dose expansions at 20/60/90 mg QD in PARPi-naive pts (Part B).
    • Study Status
    Indicates the current recruitment status or the expanded access status
    Recruitment Complete

    Requirements information
    Inclusion criteria
    • Age > or = 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 > or = 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).
    • Hb > or = 9.0 g/dL were required
    • Provision of signed and dated, written informed consent prior to any study specific procedures, sampling and analyses
    • Female subjects of childbearing potential: Must have negative pregnancy test result at screening and prior to each administration of study treatment and must use at least one highly effective method of birth control.
    • Female subjects must not breastfeed and must not donate or retrieve ova for their own use, from screening to approximately 6 months after the last dose of study treatment with IMP.
    • Non-sterilized male patients who are sexually active with a female partner of childbearing potential must use a condom with spermicide from screening to approximately 6 months after the last dose of AZD5305 IMP.
    Exclusion criteria
    • 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:
    • 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

    Clinical Study Information for Healthcare Providers

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    Study Locations

    Location
    Investigator
    Status
    Condition(s) Treated at Site
    Location
    START Madrid, Spain (CIOCC)
    Madrid, Spain, 28050
    Investigator
    Emiliano Calvo
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Ovarian
    Breast Cancers
    Pancreas
    Prostate
    Non-Small Cell Lung Cancer
    Bowel (Colorectal)
    Bladder
    Gastric
    Bile Duct
    Cervical cancer
    Endometrial
    Small Cell Lung
    Location
    START Madrid, Spain (FJD)
    Madrid, Spain, 28040
    Investigator
    Bernard Doger de Speville
    Status
    Recruitment Complete
    Condition(s) Treated at Site
    Ovarian
    Breast Cancers
    Pancreas
    Prostate
    Non-Small Cell Lung Cancer
    Bowel (Colorectal)
    Bladder
    Gastric
    Bile Duct
    Cervical cancer
    Endometrial
    Small Cell Lung