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

ConditionNeoplasm
Trial statusNot yet recruiting
Trial phasePhase 1
Trial typeInterventional
Biological sexAll
Age18+
SponsorAstraZeneca

About this trial

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.

Eligibility criteria

This trial does not accept healthy volunteers

Qualifiers

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.

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.

Disqualifiers

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

Trial design

Design model

Single group

Treatments tested in this trial

  • [14C] AZD6738

    Drug

    radiolabeled AZD6738 / ceralasertib

  • AZD6738 / ceralasertib

    Drug

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

Treatment groups

8 Participants
are divided into 1 treatment group
Group A: Primary Treatment Arm - AZD6738Experimental treatment 2 interventions

Trial outcomes

Primary outcomes

1

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

Time frame
Through end of Part A, approximately 5 weeks including screening period
2

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

Time frame
Through end of Part B, approximately 10 weeks including screening period
3

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

Time frame
Through end of the part B, approximately 10 weeks (Including screening period)
4

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

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

Secondary outcomes

1

To provide biologic samples for metabolic profiling and identification after oral dose of [14C]-Ceralasertib (Part B)

Quantification and identification of major metabolites of Ceralasertib in plasma and excreta (will be reported separately)

Time frame
Through end of the part B, approximately 10 weeks (Including screening period)
2

To assess the safety of Ceralasertib in participants with NSCLC, ovarian cancer, or endometrial cancer (Parts A and B)

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

Time frame
Through study completion, approximately 9 - 11 weeks, with screening included

Other outcomes

Sponsors and contacts

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