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

Study Status: Active, not recruiting
Recruit Status: Active, not recruiting
Study Type: Interventional

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

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 Summary:

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v1.1 There will be a data cut-off after all patients have completed at least 12 weeks of treatment with AZD6094 or withdrawn.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 fol
Sponsor: AstraZeneca

Current Primary Outcome: Objective tumour response (partial response [PR] or complete response [CR]) as assessed by RECIST v1.1 [ Time Frame: Every 6 weeks until objective disease progression (estimated 12 months). After database lock (DBL) tumour assessments will be performed every 12 weeks until objective disease progression. ]

The response rate is defined as the percentage of subjects with at least one visit response of complete or partial response that is confirmed at least 4 weeks later.


Original Primary Outcome: Assess the antitumor activity of AZD6094 as measured by Overall Response Rate [ Time Frame: Up to 7 months ]

The response rate is defined as the number (%) of subjects with at least one visit response of complete or partial response that is confirmed at least 4 weeks later.


Current Secondary Outcome:

  • Assess progression-free survival (PFS) in patients with PRCC and in the subgroup of MET-positive patients. [ Time Frame: Up to 7 months ]
    Progression-free survival is defined as the time from first dose until the date of objective disease progression or death (by any cause in the absence of progression).
  • Assess the safety and tolerability of AZD 6094 [ Time Frame: Up to 7 months ]
    Safety profiles will be assessed in terms of AEs and laboratory data, vital signs and ECGs that will be collected for all patients.
  • Pharmacokinetics (PK) of AZD6094 and major metabolites M2 and M3 for AUC, AUC(0-24), AUC(0-t), AUCss, Cmax, Css max, and Css min [ Time Frame: Cycle 1 Day 8 and 15, Cycle 2 Day 1, Cycle 3, Day 1, and Cycle 4, Day 1 ]
    Characterise the pharmacokinetics (PK) of AZD6094 and the major metabolites M2 and M3 following administration to steady state after multiple dosing when given orally.
  • Assess duration of response according to RECIST v1.1 [ Time Frame: Up to 7 months ]
    Duration of response is defined as the time from the date of first documented response until the date of documented progression or any cause death. In the case where a subject does not progress following response, the duration of response will be the same as the PFS censoring time.
  • Assess duration of overall survival according to RECIST v1.1 [ Time Frame: Up to 7 months ]
    Overall survival (OS) is defined as the time from the date of first treatment until death due to any cause.
  • Change from baseline in target lesion tumour size [ Time Frame: 12 weeks ]
    The percentage change from baseline in target lesion tumour size will be measured at 12 weeks.
  • Pharmacodynamic (PDc) effects will be assessed by measuring biomarkers phospho-cMET and total-cMET. [ Time Frame: 6 weeks, 12 weeks, at discontinuation of treatment, and at disease progression. ]
    The pharmacodynamic effects of AZD6094 will be evaluated in tumour tissue paired biopsies (a pre-dose tumour biopsy and paired tumour biopsies post-dose). The biomarkers investigated may include, but are not limited to, phospho-cMet and total-cMet.


Original Secondary Outcome:

  • Assess progression free survival [ Time Frame: Up to 7 months ]
    Progression-free survival is defined as the time from randomisation until the date of objective disease progression or death (by any cause in the absence of progression) regardless of whether the subject withdraws from randomised therapy or receives another anti-cancer therapy prior to progression.
  • Assess the safety and tolerability of AZD 6094 [ Time Frame: Up to 7 months ]
    Safety profiles will be assessed in terms of AEs and laboratory data, vital signs and ECGs that will be collected for all patients.
  • Pharmacokinetics (PK) of AZD6094 and major metabolites M2 and M3 for AUC, AUC(0-24), AUC(0-t), AUCss, Cmax, Css max, and Css min [ Time Frame: Cycle 1 Day 8 and 15, Cycle 2 Day 1, Cycle 3, Day 1, and Cycle 4, Day 1 ]
    Characterise the pharmacokinetics (PK) of AZD6094 and the major metabolites M2 and M3 following administration to steady state after multiple dosing when given orally.
  • Assess change in target lesion tumor size from baseline [ Time Frame: Up to 7 months ]
    Change in Target Lesion is percentage change from baseline in tumor size at 12 weeks. This is based on RECIST target lesion measurements taken at baseline and at week 12. Target lesions are measureable tumour lesions.
  • Assess duration of response according to RECIST v1.1 [ Time Frame: Up to 7 months ]
    Duration of response is defined as the time from the date of first documented response until the date of documented progression or any cause death. In the case where a subject does not progress following response, the duration of response will be the same as the PFS censoring time.
  • Assess duration of overall survival according to RECIST v1.1 [ Time Frame: Up to 7 months ]
    Overall Survival (OS) - Overall survival is defined as the time from the date of randomization until death due to any cause.


Information By: AstraZeneca

Dates:
Date Received: April 23, 2014
Date Started: April 2014
Date Completion: January 2017
Last Updated: September 21, 2016
Last Verified: September 2016