Human ADME Study of [14C]-Ceralasertib (AZD6738) and Absolute Bioavailability of Ceralasertib

Официальное название

A Phase I, Open-label Study to Assess the Absolute Bioavailability of Ceralasertib (AZD6738) and Absorption, Distribution, Metabolism, and Excretion (ADME) of [14C]-Ceralasertib in Patients With Non-small Cell Lung Cancer, Ovarian Cancer, or Endometrial Cancer

Обзор

This is an open-label, two-part study in participants with NSCLC, ovarian cancer, or endometrial cancer and will be conducted at multiple study sites. Participants will be assessed for study eligibility prior to admission to the study site. Part A will assess the absolute bioavailability, determine the excretory routes of \[14C\]-Ceralasertib, and evaluate the PK parameters of a Ceralasertib oral dose and a radiolabelled IV microdose of \[14C\]-Ceralasertib. Participants will be admitted to the study site pre-dose Part A and will remain at the study site for excreta (urine and faeces) collections, PK sampling and safety assessments. A washout period days will be observed between dosing in Part A and Part B. Part B will assess the ADME of \[14C\]-Ceralasertib. Participants will be readmitted to the study site for Part B and will remain at the study site for excreta (urine, faeces, and any vomitus) collections, PK sampling, and safety assessments. Participants will return to the study site for a Follow-up Visit after the last dose of Ceralasertib which will include routine safety assessments. After the completion of Parts A and B, and following the Follow-up Visit, participants may be allowed further access to Ceralasertib if in the opinion of the investigator and medical monitor they may derive clinical benefit.

Вмешательства

• Препарат [14C] AZD6738
  radiolabeled AZD6738 / ceralasertib
• Препарат AZD6738 / ceralasertib
  Ceralasertib (AZD6738) is a potent, selective inhibitor of the serine/threonine-specific protein kinase ATR

Первичные конечные точки

• To evaluate absolute bioavailability Ceralasertib and PK of Ceralasertib and [14C]-Ceralasertib after administration of oral dose of Ceralasertib and IV [14C]-Ceralasertib (Part A [Срок оценки: Through end of Part A, approximately 5 weeks including screening period]
• To determine the rates and major excretory routes of Ceralasertib and its metabolites after IV dose of [14C]-Ceralasertib (Part A) and a oral dose of [14C]-Ceralasertib (Part B) [Срок оценки: Through end of Part B, approximately 10 weeks including screening period]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To characterise the PK of Ceralasertib and total radioactivity following oral dose of [14C]-Ceralasertib including the extent of distribution into blood cells (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]

Вторичные конечные точки (2)

• To provide biologic samples for metabolic profiling and identification after oral dose of [14C]-Ceralasertib (Part B) [Срок оценки: Through end of the part B, approximately 10 weeks (Including screening period)]
• To assess the safety of Ceralasertib in participants with NSCLC, ovarian cancer, or endometrial cancer (Parts A and B) [Срок оценки: Through study completion, approximately 9 - 11 weeks, with screening included]

Критерии участия

Критерии включения

• Participants are eligible to be included in the study only if all of the following criteria apply:

Age

• 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.

Type of Participant and Disease Characteristics

• Sufficient ECOG performance status, life expectancy, and ability to swallow and retain oral medication
• Adequate organ and marrow function
• Willingness and ability to comply with study and follow-up procedures.
• Able and willing to stay in hospital for specified residential periods following administration of Ceralasertib/\[14C\]-Ceralasertib
• Regular bowel movements
• Participants with NSCLC must have appropriately documented NSCLC diagnosis, mutation status, treatment history, and disease status according to protocol-specified eligibility criteria
• Participants with Ovarian cancer must have appropriately documented ovarian cancer diagnosis, mutation status, treatment history, and disease status according to protocol-specified eligibility criteria 9. Participants with Endometrial cancer must have appropriately documented endometrial cancer diagnosis, treatment history, and disease status according to protocol-specified eligibility criteria 10. Sex and Contraceptive/Barrier Requirements: Contraceptive use by men or women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies 11. Informed Consent: patient must be capable of giving signed informed consent as described in Appendix A which includes compliance with the requirements and restrictions listed in the ICF and in this protocol.

Критерии исключения

• Participants are excluded from the study if any of the following criteria apply:

• History of Diagnosis of protocol-specified medical conditions
• Spinal cord compression or brain metastasis prior to start of study intervention unless asymptomatic and stable
• Persistent toxicities (CTCAE Grade ≥ 2), with the exception of alopecia and vitiligo, caused by previous anticancer therapy.
• History of allogenic organ transplant or autoimmune or inflammatory disorders requiring use of immunosuppressive medications with some protocol specified conditions/exceptions
• Any medical or surgical condition that would preclude adequate absorption of Ceralasertib
• Inadequate cardiac function / status or other cardiovascular diseases
• Participants with active infection requiring systemic antibiotics, antifungal or antiviral drugs
• Any evidence of severe or uncontrolled systemic disease, as judged by the investigator that would make it undesirable for the participant to participate in the study or would jeopardise compliance with the protocol
• Protocol-specified prior/concomitant therapy exclusions
• Protocol-specified prior/concurrent clinical study experience
• Other Exclusions including but not limited to tobacco/nicotine and/or alcohol use, or drug/alcohol abuse history
• Not currently pregnant, breast-feeding, or planning to become pregnant

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Не применимо

Модель

Одна группа

Маскирование

Открытое

Основная цель

Фундаментальное исследование

Центры проведения

Великобритания · 2 центра

• Research Site — Liverpool
• Research Site — London

Идентификаторы

NCT: NCT06754761 · D533BC00002

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

Открыть это исследование на ClinicalTrials.gov ↗