A Phase II Trial to Evaluate the Efficacy of AZD6094 (HMPL-504) in Patients With Papillary Renal Cell Carcinoma (PRCC)

Phase 2

Completed

Conditions: Papillary Renal Cell Cancer

Interventions: Drug: AZD6094

Registration Number: NCT02127710

Lead Sponsor: AstraZeneca

Brief Summary: This is an open-label, single-arm, multicentre, global, phase II study designed to evaluate the efficacy and safety of AZD6094 in patients with papillary renal cell carcinoma (PRCC) who are treatment naïve or previously treated.

An independent central pathology review of tumour samples will be used to confirm the diagnosis of PRCC of all patients enrolling. However, locally available pathology results confirming PRCC will be allowed for timely study entry.

Detailed Description: The study will comprise two stages. In Stage 1 approximately 20 patients will be enrolled. This group is considered sufficient to provide preliminary assessment of the anti-tumour activity of AZD6094 in the form of non-binding futility analysis.

If ≤ 2 tumour responses are observed in the first 20 evaluable patients termination of the study will be considered taking into account the relevant molecular profile of the patients and additional information from related studies in the drug development programme.

All patients entering the study will take AZD6094 600 mg by mouth (PO) once daily (QD). Treatment will be given continuously.

Following the baseline assessment, efficacy will be assessed by objective tumour assessments every 6 weeks (±7 days), for the first 12 months and every 12 weeks thereafter until objective disease progression as defined by RECIST v1.1 There will be a data cut-off after all patients have completed at least 12 weeks of treatment with AZD6094 or withdrawn. The database will be locked and data analysis will be performed on this dataset.

Any patients still receiving study drug at the time of data cut-off will be able to continue to receive AZD6094 while deriving clinical benefit. Such patients will continue to be monitored for the occurrence of serious adverse events up to 28 days after the last dose of AZD6094.

After database lock (DBL) tumour assessments will be performed every 12 weeks (±7 days) until objective disease progression as defined by RECIST v1.1.

Patients discontinuing treatment due to documented disease progression will enter a survival follow-up period, where they will be followed for the initiation of subsequent anti-cancer therapies every 3 months until death, loss to follow-up or withdrawal of consent, whichever comes first.

Patients discontinuing treatment prior to documented disease progression will enter a progression-free survival follow-up period where they will continue to have disease assessments every 6 weeks (±7 days) for the first 12 months of follow-up and every 12 weeks thereafter until objective disease progression as defined by RECIST v1.1, death, loss to follow-up or withdrawal of consent, whichever comes first. After DBL, tumour assessments will be performed in the progression free survival patient population every 12 weeks (±7 days) until objective disease progression as defined by RECIST v1.1

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 111

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
AZD6094 600 mg daily continuously	AZD6094	All patients entering the study will take AZD6094 600 mg by mouth (PO) once daily (QD). Treatment will be given continuously.

Primary Outcome Measures

Name	Time	Method
Objective Response Rate (RECIST Version 1.1)	Up to 12 months	The primary outcome measure was Objective Response Rate (ORR), defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to Response Evaluation Criteria for Solid Tumours (RECIST) v1.1.
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set	12 Months	The primary outcome measure was ORR, defined as the proportion of patients with either a complete response or a partial response by investigator assessment according to RECIST v1.1.
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set	12 Months	The primary outcome measure was ORR, defined as the proportion of patients with either a confirmed complete response/partial response by investigator assessment according to RECIST v1.1.

Secondary Outcome Measures

Name	Time	Method
Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set	Up to 12 months
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose (Time Zero to Last Measurement)	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Peak Plasma Concentration of AZD6094 Following Single Dose	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set	Up to 12 months
Overall Survival Stratified by c-MET Status in the Safety Analysis Set	Up to 12 months
Time to Peak Plasma Concentration of AZD6094 After Single Dose	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Elimination Half-Life of AZD6094 After Single Dose	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set	12 Weeks (at 12 weeks timepoint)	12 week summary for patients in the Efficacy analysis set, by MET status. The numbers of patients analysed represent the numbers evaluable at the 12 week timepoint.
Duration of Response	Up to 12 months	Duration of Response is the time from the first documentation of confirmed complete response/partial response until the date of progression, or death in the absence of progression. There were 8 responders: one of whom subsequently progressed or died and seven of whom were still classified as responders at the time of data cut-off and were therefore censored. It was not possible to determine a median or 75th percentile.
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Apparent Total Clearance of AZD6094 From Plasma After Single Dose	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
Mean Residence Time of AZD6094 After Single Dose	24 Hours	The number of patients analysed represent the number of evaluable PK parameters for this endpoint.
Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set	Up to 12 months
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set.	12 Weeks (at 12 week timepoint)	12 week summary for patients in the Safety analysis set by MET Status. The number of patients analysed represent the number of evaluable patients at the 12 week timepoint.
Apparent Volume of Distribution of AZD6094 Following Single Dose	24 Hours	The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.