Clinical Trials /

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

NCT04644068

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.

Related Conditions:
  • Breast Carcinoma
  • Ovarian Carcinoma
  • Pancreatic Carcinoma
  • Prostate Carcinoma
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

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

Clinical Trial IDs

  • ORG STUDY ID: D9720C00001
  • NCT ID: NCT04644068

Conditions

  • Ovarian Cancer
  • Breast Cancer
  • Pancreatic Cancer
  • Prostate Cancer

Interventions

DrugSynonymsArms
AZD5305Module 1: AZD5305 Monotherapy
PaclitaxelModule 2: AZD5305 + Paclitaxel
CarboplatinModule 3: AZD5305 + Paclitaxel + Carboplatin

Purpose

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.
    

Trial Arms

NameTypeDescriptionInterventions
Module 1: AZD5305 MonotherapyExperimentalAZD5305 Monotherapy
  • AZD5305
Module 2: AZD5305 + PaclitaxelExperimentalAZD5305 + Paclitaxel
  • AZD5305
  • Paclitaxel
Module 3: AZD5305 + Paclitaxel + CarboplatinExperimentalAZD5305 + Paclitaxel + Carboplatin
  • AZD5305
  • Paclitaxel
  • Carboplatin

Eligibility Criteria

        Key Inclusion 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 per RECIST v1.1

          -  Adequate organ and marrow function as defined by the protocol.

          -  For expansion cohorts: Provision of formalin-fixed and paraffin embedded (FFPE) tumour
             specimen is mandatory 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).

        Key Exclusion Criteria:

          -  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 longer) 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

          -  Concomitant use of medications or herbal supplements known to be cytochrome P450 3A4
             (CYP3A4) strong and moderate 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

          -  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.

               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)
      
Maximum Eligible Age:130 Years
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:The number of subjects with adverse events/serious adverse events
Time Frame:From time of Informed Consent to 28 days post last dose (approximately 1 year)
Safety Issue:
Description: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

Secondary Outcome Measures

Measure:Percentage change in target lesion
Time Frame:From Screening to confirmed progressive disease (approximately 1 year)
Safety Issue:
Description:Change in target lesion size from baseline, as defined by RECIST 1.1.
Measure:Objective Response Rate
Time Frame:From Screening to confirmed progressive disease (approximately 1 year)
Safety Issue:
Description:Best response until progression, as defined by RECIST 1.1.
Measure:Duration of response
Time Frame:From Screening to confirmed progressive disease (approximately 1 year)
Safety Issue:
Description:Time from response to progression, as defined by RECIST 1.1.
Measure:Progression Free Survival
Time Frame:From Screening to confirmed progressive disease (approximately 1 year)
Safety Issue:
Description:Time from C1D1 to progression or death, as defined by RECIST 1.1.
Measure:Time to response
Time Frame:From Screening to confirmed progressive disease (approximately 1 year)
Safety Issue:
Description:Time from C1D1 to complete or partial response, as defined by RECIST 1.1.
Measure:Effects of AZD5305 on Ph2AX (Ser139) PD biomarker
Time Frame:From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days)
Safety Issue:
Description:Measure change from baseline in pH2AX
Measure:Module 1: Area under curve (AUC)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description: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.
Measure:Module 1: Maximum plasma concentration of the drug (Cmax)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description:The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
Measure:Module 1: The time taken to reach the maximum concentration (Tmax)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description:The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
Measure:Module 2: Area under curve (AUC)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description: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.
Measure:Module 2: Maximum plasma concentration of the drug (Cmax)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description:The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
Measure:Module 2: The time taken to reach the maximum concentration (Tmax)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description:The concentration of AZD5305 in plasma will be determined (Tmax will be derived).
Measure:Module 3: Area under curve (AUC)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description: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.
Measure:Module 3: Maximum plasma concentration of the drug (Cmax)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description:The concentration of AZD5305 in plasma will be determined (Cmax will be derived).
Measure:Module 3: The time taken to reach the maximum concentration (Tmax)
Time Frame:At predefined intervals throughout the treatment period (approximately 12 weeks)
Safety Issue:
Description:The concentration of AZD5305 in plasma will be determined (Tmax will be derived).

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:AstraZeneca

Trial Keywords

  • PARP inhibitor
  • Breast Cancer
  • Pancreatic Cancer
  • Prostate Cancer
  • Ovarian Cancer

Last Updated

November 25, 2020