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

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

INTRODUCTION

  • Org Study ID: D9720C00001
  • Secondary ID: N/A
  • NCT ID: NCT04644068
  • Sponsor: 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.

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.

  • Overall Status
    Recruiting
  • Start Date
    November 12, 2020
  • Phase
    Phase 1, Phase 2
  • Study Type
    Interventional

PRIMARY OUTCOMES

Primary Outcome 1 - Measure: The number of subjects with adverse events/serious adverse events

Primary Outcome 1 - Timeframe: From time of Informed Consent to 28 days post last dose (approximately 1 year). 40 days post last dose for Module 4

Primary Outcome 2 - Measure: The number of subjects with dose-limiting toxicity (DLT), as defined in the protocol.

Primary Outcome 2 - Timeframe: From first dose of study treatment until the end of Cycle 1.

CONDITION

  • Ovarian Cancer
  • Breast Cancer
  • Pancreatic Cancer
  • Prostate Cancer
  • Additional Indications Below for Module 4 and 5
  • Non-small Cell Lung Cancer
  • Small Cell Lung Cancer
  • Colorectal Cancer
  • Bladder Cancer
  • Gastric Cancer
  • Biliary Cancer
  • Cervical Cancer
  • Endometrial Cancer

ELIGIBILITY

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 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).
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 shorter) 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. 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:
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; subjects with atrial fibrillation and optimally controlled ventricular rate (< 100 beats per minute) are permitted. - 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).
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

Gender: All

Minimum Age: 18 Years

Maximum Age: N/A

Healthy Volunteers: No

OFFICIAL INFORMATION

Name: Timothy Yap

Role: Principal Investigator

Affiliation: M.D. Anderson Cancer Center

Overall Contact

Name: Timothy Yap

Phone: 1-877-240-9479, +1-877-400-4656

Email: information.center@astrazeneca.com, AstraZeneca@CareboxHealth.com

LOCATION

Facility Status Contact
Facility: Research Site
New York, New York 10021
United States
Status: Recruiting Contact: N/A
Facility: Research Site
Oklahoma City, Oklahoma 73104
United States
Status: Recruiting Contact: N/A
Facility: Research Site
Houston, Texas 77030
United States
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Facility: Research Site
Melbourne, 3000
Australia
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Facility: Research Site
Vancouver, British Columbia V5Z 1K1
Canada
Status: Recruiting Contact: N/A
Facility: Research Site
Toronto, Ontario M5G 2M9
Canada
Status: Recruiting Contact: N/A
Facility: Research Site
Montreal, Quebec H2X 0A9
Canada
Status: Recruiting Contact: N/A
Facility: Research Site
Montreal, Quebec H3T 1E2
Canada
Status: Recruiting Contact: N/A
Facility: Research Site
Changsha, 410013
China
Status: Recruiting Contact: N/A
Facility: Research Site
Chengdu, 610041
China
Status: Recruiting Contact: N/A
Facility: Research Site
Chongqing, 400030
China
Status: Recruiting Contact: N/A
Facility: Research Site
Guangzhou, 510060
China
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Facility: Research Site
Shanghai, 200032
China
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Facility: Research Site
Taiyuan, 030001
China
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Facility: Research Site
Wuhan, 430079
China
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Facility: Research Site
Brno, 656 53
Czechia
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Facility: Research Site
Budapest, 1062
Hungary
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Facility: Research Site
Budapest, 1083
Hungary
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Facility: Research Site
Budapest, 1122
Hungary
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Facility: Research Site
Milano, 20132
Italy
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Facility: Research Site
Milan, 20141
Italy
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Facility: Research Site
Modena, 41125
Italy
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Facility: Research Site
Napoli, 80131
Italy
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Facility: Research Site
Padova, 35128
Italy
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Facility: Research Site
Roma, 00168
Italy
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Facility: Research Site
Chuo-ku, 104-0045
Japan
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Facility: Research Site
Koto-ku, 135-8550
Japan
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Facility: Research Site
Seoul, 03080
Korea, Republic of
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Facility: Research Site
Seoul, 03722
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Research Site
Seoul, 05505
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Research Site
Seoul, 06351
Korea, Republic of
Status: Recruiting Contact: N/A
Facility: Research Site
Bydgoszcz, 85-796
Poland
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Facility: Research Site
Gdynia, 81-519
Poland
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Facility: Research Site
Grzepnica, 72-003
Poland
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Facility: Research Site
Lublin, 20-090
Poland
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Facility: Research Site
Toruń, 87-100
Poland
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Facility: Research Site
Warszawa, 02-781
Poland
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Facility: Research Site
Barcelona, 08035
Spain
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Facility: Research Site
Madrid, 28041
Spain
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Facility: Research Site
Madrid, 28050
Spain
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Facility: Research Site
Málaga, 29010
Spain
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Facility: Research Site
Sevilla, 41013
Spain
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Facility: Research Site
Cambridge, CB2 0QQ
United Kingdom
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Facility: Research Site
Manchester, M20 4BX
United Kingdom
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Facility: Research Site
Oxford, OX3 7LE
United Kingdom
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Facility: Research Site
Sutton, SM2 5PT
United Kingdom
Status: Recruiting Contact: N/A