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

Phase 1

Not yet recruiting

• Conditions: Neoplasm
• Interventions: Drug: [14C] AZD6738; Drug: AZD6738 / ceralasertib

• Registration Number: NCT06754761
• Lead Sponsor: AstraZeneca

Brief Summary

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2024-11-04
• Status Verified: 2024-12
• Study First Submitted QC: 2024-12-23
• Last Update Submitted: 2024-12-23
• Study First Posted: 2025-01-01
• Last Update Posted: 2025-01-01
• Study Start: 2025-01-17
• Primary Completion: 2025-08-08
• Study Completion: 2025-08-08

Recruitment & Eligibility

• Status: NOT_YET_RECRUITING
• Sex: All
• Target Recruitment: 8

Inclusion Criteria

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

Age

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.

   Type of Participant and Disease Characteristics

2. Sufficient ECOG performance status, life expectancy, and ability to swallow and retain oral medication

3. Adequate organ and marrow function

4. Willingness and ability to comply with study and follow-up procedures.

5. Able and willing to stay in hospital for specified residential periods following administration of Ceralasertib/[14C]-Ceralasertib

6. Regular bowel movements

7. Participants with NSCLC must have appropriately documented NSCLC diagnosis, mutation status, treatment history, and disease status according to protocol-specified eligibility criteria

8. 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.

Exclusion Criteria

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

  1. History of Diagnosis of protocol-specified medical conditions
  2. Spinal cord compression or brain metastasis prior to start of study intervention unless asymptomatic and stable
  3. Persistent toxicities (CTCAE Grade ≥ 2), with the exception of alopecia and vitiligo, caused by previous anticancer therapy.
  4. History of allogenic organ transplant or autoimmune or inflammatory disorders requiring use of immunosuppressive medications with some protocol specified conditions/exceptions
  5. Any medical or surgical condition that would preclude adequate absorption of Ceralasertib
  6. Inadequate cardiac function / status or other cardiovascular diseases
  7. Participants with active infection requiring systemic antibiotics, antifungal or antiviral drugs
  8. 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
  9. Protocol-specified prior/concomitant therapy exclusions
  10. Protocol-specified prior/concurrent clinical study experience
  11. Other Exclusions including but not limited to tobacco/nicotine and/or alcohol use, or drug/alcohol abuse history
  12. Not currently pregnant, breast-feeding, or planning to become pregnant

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Primary Treatment Arm - AZD6738	[14C] AZD6738	Part A - oral dose of Ceralasertib and a radiolabelled IV microdose of \[14C\]-Ceralasertib Part B - oral dose of \[14C\]-Ceralasertib
Primary Treatment Arm - AZD6738	AZD6738 / ceralasertib	Part A - oral dose of Ceralasertib and a radiolabelled IV microdose of \[14C\]-Ceralasertib Part B - oral dose of \[14C\]-Ceralasertib

Primary Outcome Measures

Name	Time	Method
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	Through end of Part A, approximately 5 weeks including screening period	Absolute bioavailability (F) of Ceralasertib and PK parameters
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)	Through end of Part B, approximately 10 weeks including screening period	\[14C\]-Ceralasertib (Part A) or total radioactivity (Part B) recovery in urine and faeces
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)	Through end of the part B, approximately 10 weeks (Including screening period)	Pharmacokinetic activity of ceralasertib present in urine

Secondary Outcome Measures

Name	Time	Method
To provide biologic samples for metabolic profiling and identification after oral dose of [14C]-Ceralasertib (Part B)	Through end of the part B, approximately 10 weeks (Including screening period)	Quantification and identification of major metabolites of Ceralasertib in plasma and excreta (will be reported separately)
To assess the safety of Ceralasertib in participants with NSCLC, ovarian cancer, or endometrial cancer (Parts A and B)	Through study completion, approximately 9 - 11 weeks, with screening included	Incidence and severity of AEs Incidence of laboratory abnormalities, based on haematology, clinical chemistry, and urinalysis test results 12-lead ECG parameters Vital signs measurements Physical examinations

Trial Locations

Locations (1)

Research Site; 🇬🇧 London, United Kingdom