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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04644068
Recruitment Status : Recruiting
First Posted : November 25, 2020
Last Update Posted : January 19, 2021
Sponsor:
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Ovarian Cancer Breast Cancer Pancreatic Cancer Prostate Cancer Drug: AZD5305 Drug: Paclitaxel Drug: Carboplatin Phase 1

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.

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 612 participants
Allocation: Non-Randomized
Intervention Model: Sequential Assignment
Intervention 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) Each Module has 2 study parts: Part A consisting of dose-escalation cohorts and Part B, consisting of expansion cohorts.
Masking: None (Open Label)
Primary Purpose: Treatment
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
Actual Study Start Date : November 12, 2020
Estimated Primary Completion Date : July 25, 2025
Estimated Study Completion Date : July 25, 2025


Arm Intervention/treatment
Experimental: Module 1: AZD5305 Monotherapy
AZD5305 Monotherapy
Drug: AZD5305
Oral PARP inhibitor

Experimental: Module 2: AZD5305 + Paclitaxel
AZD5305 + Paclitaxel
Drug: AZD5305
Oral PARP inhibitor

Drug: Paclitaxel
IV Anti-microtubule agent

Experimental: Module 3: AZD5305 + Carboplatin with or without Paclitaxel
AZD5305 + Carboplatin with or without Paclitaxel
Drug: AZD5305
Oral PARP inhibitor

Drug: Paclitaxel
IV Anti-microtubule agent

Drug: Carboplatin
Platinum chemotherapeutic




Primary Outcome Measures :
  1. 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) ]
    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

  2. 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. Approximately 35 days. ]
    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 and which includes pre-defined haematological, cardiac and non-haematological toxicities.


Secondary Outcome Measures :
  1. Percentage change in target lesion [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]
    Change in target lesion size from baseline, as defined by RECIST 1.1.

  2. Objective Response Rate [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]
    Best response until progression, as defined by RECIST 1.1.

  3. Duration of response [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]
    Time from response to progression, as defined by RECIST 1.1.

  4. Progression Free Survival [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]
    Time from C1D1 to progression or death, as defined by RECIST 1.1.

  5. Time to response [ Time Frame: From Screening to confirmed progressive disease (approximately 1 year) ]
    Time from C1D1 to complete or partial response, as defined by RECIST 1.1.

  6. Effects of AZD5305 on Ph2AX (Ser139) PD biomarker [ Time Frame: From Cycle 0 Day 1 to Cycle 1 Day 15 (approximately 21 days) ]
    Measure change from baseline in pH2AX

  7. Module 1: Area under curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    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.

  8. Module 1: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    The concentration of AZD5305 in plasma will be determined (Cmax will be derived).

  9. Module 1: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    The concentration of AZD5305 in plasma will be determined (Tmax will be derived).

  10. Module 2: Area under curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    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.

  11. Module 2: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    The concentration of AZD5305 in plasma will be determined (Cmax will be derived).

  12. Module 2: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    The concentration of AZD5305 in plasma will be determined (Tmax will be derived).

  13. Module 3: Area under curve (AUC) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    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.

  14. Module 3: Maximum plasma concentration of the drug (Cmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    The concentration of AZD5305 in plasma will be determined (Cmax will be derived).

  15. Module 3: The time taken to reach the maximum concentration (Tmax) [ Time Frame: At predefined intervals throughout the treatment period (approximately 12 weeks) ]
    The concentration of AZD5305 in plasma will be determined (Tmax will be derived).



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
    4. 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 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)

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04644068


Contacts
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Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com

Locations
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United States, New York
Research Site Not yet recruiting
New York, New York, United States, 10021
United States, Texas
Research Site Recruiting
Houston, Texas, United States, 77030
Australia
Research Site Not yet recruiting
Melbourne, Australia, 3000
Sponsors and Collaborators
AstraZeneca
Investigators
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Principal Investigator: Timothy Yap M.D. Anderson Cancer Center
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Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT04644068    
Other Study ID Numbers: D9720C00001
First Posted: November 25, 2020    Key Record Dates
Last Update Posted: January 19, 2021
Last Verified: January 2021

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by AstraZeneca:
PARP inhibitor
Breast Cancer
Pancreatic Cancer
Prostate Cancer
Ovarian Cancer
Additional relevant MeSH terms:
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Prostatic Neoplasms
Pancreatic Neoplasms
Ovarian Neoplasms
Neoplasms by Site
Neoplasms
Genital Neoplasms, Male
Urogenital Neoplasms
Prostatic Diseases
Digestive System Neoplasms
Endocrine Gland Neoplasms
Digestive System Diseases
Pancreatic Diseases
Endocrine System Diseases
Ovarian Diseases
Adnexal Diseases
Genital Neoplasms, Female
Gonadal Disorders
Paclitaxel
Carboplatin
Antineoplastic Agents, Phytogenic
Antineoplastic Agents
Tubulin Modulators
Antimitotic Agents
Mitosis Modulators
Molecular Mechanisms of Pharmacological Action