AZD5305 hADME in Patients With Advanced Solid Malignancies

Launched by ASTRAZENECA · Nov 27, 2024

Keywords

ClinConnect Summary

This clinical trial is studying a new medication called Saruparib (AZD5305) to understand how it moves through the body and how well it is absorbed, distributed, broken down, and eliminated. The study is for adults aged 18 and older who have locally advanced or metastatic solid tumors, which are types of cancer that have spread and for which there are no effective standard treatments. To participate, candidates must be in relatively good health, have a life expectancy of at least 12 weeks, and be willing to stay in the hospital for a couple of days after taking the medication.

Participants in the trial will receive Saruparib either as a single oral dose or as an injection, and researchers will collect samples of blood, urine, and other bodily fluids to study how the drug behaves in their bodies. This is an early-stage trial, which means it's one of the first steps in testing this new treatment. It's important for potential participants to know that they will be closely monitored throughout the study, and there are specific criteria that disqualify individuals with certain health conditions. This is to ensure the safety of all participants and to gather accurate data on Saruparib's effects.

Gender

ALL

Eligibility criteria

• Inclusion Criteria:
• • 1. Male or female ≥ 18 years of age (or the legal age of consent in the jurisdiction in which the study is taking place), at the time of signing the ICF.
• • 2. Histologically or cytologically documented, locally advanced or metastatic solid tumour, excluding lymphoma, for which standard therapy does not exist or has proven ineffective or intolerable.
• • 3. ECOG performance status of 0 or 1 with no deterioration over the 2 weeks prior to dosing.
• • 4. Predicted life expectancy ≥ 12 weeks.
• • 5. Adequate organ and marrow function as defined in the protocol
• • 6. Willingness and ability to comply with study and follow-up procedures.
• • 7. Able and willing to stay in hospital for specified residential periods following administration of Saruparib/\[14C\]-Saruparib
• • 8. Regular bowel movements
• • 9. Body weight within normal range specified in protocol
• • 10. Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies Reproduction
• • 11. Capable of giving signed informed consent which includes compliance with the requirements and restrictions listed in the ICF and in the protocol
• Exclusion Criteria:
• • 1. Participants with a history of MDS/AML or with features suggestive of MDS/AML (as determined by prior diagnostic investigation). Specific screening for MDS/AML is not required.
• • 2. Participants with any known predisposition to bleeding
• • 3. Any history of persisting severe cytopenia due to any cause
• • 4. Refractory nausea and vomiting, chronic gastrointestinal diseases, inability to swallow the formulated product or previous significant bowel resection that would preclude adequate absorption, distribution, metabolism, or excretion of Saruparib.
• • 5. History of another primary malignancy, with some exceptions
• • 6. Persistent toxicities (CTCAE Grade ≥ 2), excluding alopecia, caused by previous anticancer therapy.
• • 7. Spinal cord compression or brain metastases for at least 4 weeks prior to start of study intervention unless asymptomatic and stable
• • 8. Abnormal cardiac function exclusions or cardiovascular disease
• • 9. History of arrhythmia
• • 10. Active HBV (positive HBsAg result) or HCV.
• • 11. Evidence of active and uncontrolled HIV infection.
• • 12. Active tuberculosis infection
• • 13. Major surgical procedure (excluding placement of vascular access) or significant traumatic injury within 4 weeks of the first dose of study intervention or an anticipated need for major surgery during the study.
• • 14. As judged by the investigator, any other evidence of diseases (such as severe or uncontrolled systemic diseases or active uncontrolled infections which, in the investigator's opinion, makes it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol.
• • 15. Any prior treatment with a PARP inhibitor or platinum chemotherapy.
• • 16. Other anticancer therapy (chemotherapy, immunotherapy, hormonal anticancer therapy, radiotherapy \[except for palliative local radiotherapy\]), biological therapy or other novel agent is not permitted until the last PK sampling is completed.
• • 17. Palliative radiotherapy with a limited field of radiation within 2 weeks or with wide field of radiation or to more than 30% of the bone marrow within 4 weeks before the first dose of study intervention
• • 18. Concomitant use of medications or herbal supplements known to be CYP3A4 strong and moderate inhibitors or inducers
• • 19. Concomitant use of drugs that are known to prolong or shorten QT and have a known risk of Torsades de Pointes
• • 20. Participants who have participated in another absorption, distribution, metabolism, and excretion study within 1 year prior to screening.
• • 21. Participation in another clinical study with a study intervention administered in the last 3 months or 5 half-lives prior to dosing, whichever is longer.
• • 22. Participants with a known hypersensitivity to Saruparib or any of the excipients of the product.
• • 23. Recent radiation exposure from clinical studies may be exclusionary
• • 24. Participants who have been administered any amount of a \[14C\]-labelled compound within the last 12 months.
• • 25. Use of tobacco- or nicotine-containing products or alcohol may be exclusionary
• • 26. Poor peripheral venous access (venous access via a port will be permitted).
• • 27. Involvement in the planning and/or conduct of the study (applies to both AstraZeneca staff and/or staff at the study site).
• • 28. Judgment by the investigator that the participant should not participate in the study if the participant is unlikely to comply with study procedures, restrictions, and requirements.
• • 29. Previous enrolment in the present study.
• • 30. For female participants only: currently pregnant (confirmed with positive pregnancy test) or planning to become pregnant, breast-feeding, or intending to donate/retrieve ova before 6 months after the last dose of Saruparib.