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

NCT06754761 | Not Yet Recruiting Phase 1

• 1 other identifier: D533BC00002
• Study Type: interventional
• Target: 8
• Locations: 1 country
• Sites: 2

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.

Conditions

Neoplasm

Keywords

non-small cell lung cancer; ovarian cancer; endometrial cancer; hADME, bioavailability; AZD6738; ceralasertib

Outcome Measures

Primary Outcomes (10)

• 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

  Absolute bioavailability (F) of Ceralasertib and PK parameters

  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)

  \[14C\]-Ceralasertib (Part A) or total radioactivity (Part B) recovery in urine and faeces

  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)

  AUCinf

  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)

  AUClast

  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)

  Cmax

  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)

  tmax

  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)

  t1/2(lambda)z

  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)

  Ratio of AUCinf of plasma Ceralasertib relative to AUCinf of plasma total radioactivity

  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)

  Ratio of AUCinf of whole blood total radioactivity relative to AUCinf of plasma total radioactivity

  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)

  Pharmacokinetic activity of ceralasertib present in urine

  Through end of the part B, approximately 10 weeks (Including screening period)

Secondary Outcomes (2)

• 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)

• 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

Study Arms (1)

Primary Treatment Arm - AZD6738

EXPERIMENTAL

Part A - oral dose of Ceralasertib and a radiolabelled IV microdose of \[14C\]-Ceralasertib Part B - oral dose of \[14C\]-Ceralasertib

Drug: [14C] AZD6738; Drug: AZD6738 / ceralasertib

Interventions

[14C] AZD6738 DRUG

radiolabeled AZD6738 / ceralasertib

Primary Treatment Arm - AZD6738

AZD6738 / ceralasertib DRUG

Ceralasertib (AZD6738) is a potent, selective inhibitor of the serine/threonine-specific protein kinase ATR

Primary Treatment Arm - AZD6738

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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/concurrent clinical study experience
• Not currently pregnant, breast-feeding, or planning to become pregnant

Sponsors & Collaborators

• AstraZeneca: lead

Study Sites (2)

Research Site

Liverpool, L7 8YA, United Kingdom

Location

Research Site

London, NW1 2PG, United Kingdom

Location

MeSH Terms

Conditions

Neoplasms; Carcinoma, Non-Small-Cell Lung; Ovarian Neoplasms; Endometrial Neoplasms

Interventions

ceralasertib

Condition Hierarchy (Ancestors)

Carcinoma, Bronchogenic; Bronchial Neoplasms; Lung Neoplasms; Respiratory Tract Neoplasms; Thoracic Neoplasms; Neoplasms by Site; Lung Diseases; Respiratory Tract Diseases; Endocrine Gland Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders; Uterine Neoplasms; Uterine Diseases

Central Study Contacts

AstraZeneca Clinical Study Information Center

CONTACT

1-877-240-9479; information.center@astrazeneca.com

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 4, 2024
• First Posted: January 1, 2025
• Study Start: January 17, 2025
• Primary Completion: August 8, 2025
• Study Completion: August 8, 2025
• Last Updated: January 1, 2025

Record last verified: 2024-12

Data Sharing

• IPD Sharing: Will share
• Time Frame: AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA PhRMA Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.
• Access Criteria: When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.

Locations

GB (2)