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
Overview
- Phase
- Phase 1
- Intervention
- [14C] AZD6738
- Conditions
- Neoplasm
- Sponsor
- AstraZeneca
- Enrollment
- 8
- Locations
- 1
- Primary Endpoint
- 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
- Status
- Not yet recruiting
- Last Updated
- last year
Overview
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.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Participants are eligible to be included in the study only if all of the following criteria apply:
- •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
Exclusion Criteria
- •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
Arms & Interventions
Primary Treatment Arm - AZD6738
Part A - oral dose of Ceralasertib and a radiolabelled IV microdose of \[14C\]-Ceralasertib Part B - oral dose of \[14C\]-Ceralasertib
Intervention: [14C] AZD6738
Primary Treatment Arm - AZD6738
Part A - oral dose of Ceralasertib and a radiolabelled IV microdose of \[14C\]-Ceralasertib Part B - oral dose of \[14C\]-Ceralasertib
Intervention: AZD6738 / ceralasertib
Outcomes
Primary Outcomes
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
Time Frame: 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)
Time Frame: 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)
Time Frame: Through end of the part B, approximately 10 weeks (Including screening period)
Pharmacokinetic activity of ceralasertib present in urine
Secondary Outcomes
- 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)