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

JRCT ID: jRCT2031210609

Registered date:15/02/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: Solid tumors
• Date of first enrollment: 15/02/2022
• Target sample size: 804
• Countries of recruitment: US,Japan,UK,Japan,Australia,Japan,Spain,Japan,South Korea,Japan,China,Japan,Russia,Japan,Hungary,Japan,Czech,Japan,Poland,Japan,Italia,Japan,Canada,Japan
• Study type: Interventional

Intervention(s)

Module1 (AZD5305 monotherapy)
Module6 (AZD5305 in combination with Camizestrant)

Outcome(s)

Primary Outcome

The number of subjects with adverse events/serious adverse events Time Frame: From time of Informed Consent to 28 days post last dose

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. ]

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Both

Include criteria

- Age 18 or more 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 or more

- 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).

Exclude 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 over 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 the clinical study protocol

- 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

Related Information

• Primary Sponsor: Hibi Kazushige
• Secondary ID(s): NCT04644068