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

March 23, 2021 updated by: AstraZeneca

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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v1.1 There will be a data cut-off after all patients have completed at least 12 weeks of treatment with AZD6094 or withdrawn.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

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
111

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Alberta
      • Calgary, Alberta, Canada, T2N 4N2
        • Research Site
      • Edmonton, Alberta, Canada, T6G 1Z2
        • Research Site
    • Ontario
      • Toronto, Ontario, Canada, M5G 2M9
        • Research Site
      • Toronto, Ontario, Canada, M4N 3M5
        • Research Site
  • Spain
      • Barcelona, Spain, 08041
        • Research Site
  • United Kingdom
      • Cambridge, United Kingdom, CB2 0QQ
        • Research Site
      • Glasgow, United Kingdom, G12 OYN
        • Research Site
      • London, United Kingdom, W1G 6AD
        • Research Site
      • London, United Kingdom, EC1M 6BQ
        • Research Site
      • Manchester, United Kingdom, M20 4BX
        • Research Site
  • United States
    • Alabama
      • Birmingham, Alabama, United States, 35294
        • Research Site
    • California
      • Duarte, California, United States, 91010
        • Research Site
      • Palo Alto, California, United States, 94305
        • Research Site
    • Florida
      • Fort Myers, Florida, United States, 33916
        • Research Site
    • Illinois
      • Chicago, Illinois, United States, 60637
        • Research Site
    • Iowa
      • Iowa City, Iowa, United States, 52242
        • Research Site
    • Massachusetts
      • Boston, Massachusetts, United States, 02215
        • Research Site
    • Michigan
      • Detroit, Michigan, United States, 48201
        • Research Site
    • New York
      • New York, New York, United States, 10021
        • Research Site
    • Pennsylvania
      • Philadelphia, Pennsylvania, United States, 19111
        • Research Site
    • Tennessee
      • Nashville, Tennessee, United States, 37203
        • Research Site
    • Texas
      • Dallas, Texas, United States, 75246
        • Research Site
      • Houston, Texas, United States, 77030
        • Research Site

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

18 years to 99 years (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion criteria

  1. Provision of informed consent prior to any study specific procedures, sampling and analyses.
  2. Histologically confirmed PRCC, which is locally advanced or metastatic.
  3. Availability of an archival tumor sample or a pre-treatment fresh tumor sample for confirmation of PRCC by a central laboratory and other biomarker
  4. Treatment naïve or have failed on previous treatment for PRCC. Previous treatments may include: targeted therapy (i.e. sunitinib, sorafenib, bevacizumab, pazopanib, temsirolimus, and everolimus), traditional immunotherapy (i.e. interferon-a, Interleukin-2), chemotherapy or a combination of chemoimmunotherapy.
  5. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
  6. At least one lesion, not previously irradiated, and not chosen for a biopsy if performed during the screening period that can be accurately measured at baseline and which is suitable for accurate repeated measurements.

  7. Adequate hematological function defined as:

    1. Absolute neutrophil count ≥1500/μL
    2. Haemoglobin ≥9 g/dL
    3. Platelets ≥100,000/μL

  8. Adequate liver function defined as:

    1. Alanine aminotransferase and aspartate aminotransferase ≤2.5 x the upper limit of normal (ULN)
    2. Total bilirubin ≤1.5 x ULN
  9. Adequate renal function defined as glomerular filtration rate ≥ 40 mL/min,
  10. Adequate coagulation parameters, defined as International Normalisation Ratio <1.5 x ULN or activated partial thromboplastin time <1.5 x ULN.
  11. Patients with known tumor thrombus or deep vein thrombosis are eligible if stable on low molecular weight heparin for ≥4 weeks.
  12. Females should be using adequate contraceptive measures should not be breast feeding, and must have a negative pregnancy test prior to start of dosing if of childbearing potential or must have evidence of non-childbearing potential
  13. Male patients should be willing to use barrier contraception, i.e. condoms.
  14. Ability to swallow and retain oral medications.
  15. Predicted life expectancy ≥12 weeks.
  16. Aged at least 18 years.
  17. Willingness and ability to comply with study and follow-up procedures.
  18. Ability to understand the nature of this study and give written informed consent.

Exclusion criteria

  1. Most recent chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents <21 days of the first dose of study treatment. Most recent targeted therapy <14 days of the first dose of study treatment.
  2. Unresolved toxicities from any prior therapy greater than Common Terminology Criteria for Adverse Events Grade 1 at the time of starting study treatment with the exception of alopecia.
  3. Prior or current treatment with a cMet inhibitor
  4. Strong inducers or inhibitors of cytochrome P450 3A4 (CYP3A4), strong inhibitors of cytochrome P450 1A2 (CYP1A2), or CYP3A4 substrates with a narrow therapeutic range within 2 weeks before the first dose of study treatment (3 weeks for St John's Wort)
  5. Wide field radiotherapy (including therapeutic radioisotopes such as strontium-89) administered ≤28 days or limited field radiation for palliation ≤7 days prior to starting study drug or has not recovered from side effects of such therapy
  6. Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
  7. Previously untreated brain metastases.
  8. Current leptomeningeal metastases or spinal cord compression due to disease.
  9. Acute or chronic liver or pancreatic disease.
  10. Uncontrolled diabetes mellitus.
  11. Gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy

  12. Any of the following cardiac diseases currently or within the last 6 months:

    1. Unstable angina pectoris
    2. Congestive heart failure (New York Heart Association ≥ Grade 2)
    3. Acute myocardial infarction
    4. Stroke or transient ischemic attack
  13. Inadequately controlled hypertension (i.e., systolic blood pressure >160 mmHg or diastolic blood pressure >100 mmHg) (patients with values above these levels must have their blood pressure controlled with medication prior to starting treatment).
  14. Mean resting correct QT interval (QTc) >470 msec obtained from triplicate electrocardiagrams
  15. Any clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiograms, e.g. complete left bundle branch block, third degree heart block, second degree heart block, PR interval >250 msec.
  16. Any factors that increase the risk of QTc prolongation or risk of arrhythmic events such as heart failure, hypokalaemia, congenital or familial long QT syndrome or family history of unexplained sudden death under 40 years of age or any concomitant medications known to prolong QT interval.
  17. Currently receiving treatment with therapeutic doses of warfarin sodium. Low molecular weight heparin is allowed.
  18. Serious active infection at the time of treatment, or another serious underlying medical condition that would impair the ability of the patient to receive protocol treatment.
  19. Known diagnosis of human immunodeficiency virus, hepatitis B, or hepatitis C.
  20. Presence of other active cancers, or history of treatment for invasive cancer ≤5years. Patients with Stage I cancer who have received definitive local treatment at least 3 years previously, and are considered unlikely to recur are eligible. All patients with previously treated in situ carcinoma (i.e., non-invasive) are eligible, as are patients with history of non-melanoma skin cancer.
  21. Psychological, familial, sociological, or geographical conditions that do not permit compliance with the protocol.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NA
  • Interventional Model: SINGLE_GROUP
  • Masking: NONE

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: AZD6094 600 mg daily continuously
All patients entering the study will take AZD6094 600 mg by mouth (PO) once daily (QD). Treatment will be given continuously.
Drug: AZD6094
AZD6094 is a potent and selective small molecule mesenchymal epithelial transition (c-MET) kinase inhibitor.
Other Names:
  • Savolitinib
  • HMPL - 504

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Objective Response Rate (RECIST Version 1.1)
Time Frame: 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.
Up to 12 months
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Efficacy Analysis Set
Time Frame: 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.
12 Months
Objective Response Rate (RECIST Version 1.1) Stratified by c-MET Status in Safety Analysis Set
Time Frame: 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.
12 Months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set
Time Frame: Up to 12 months
Up to 12 months
Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set
Time Frame: Up to 12 months
Up to 12 months
Progression Free Survival Stratified by c-MET Status in the Safety Analysis Set
Time Frame: Up to 12 months
Up to 12 months
Overall Survival Stratified by c-MET Status in the Safety Analysis Set
Time Frame: Up to 12 months
Up to 12 months
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set
Time Frame: 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.
12 Weeks (at 12 weeks timepoint)
Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Safety Analysis Set.
Time Frame: 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.
12 Weeks (at 12 week timepoint)
Duration of Response
Time Frame: 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.
Up to 12 months
Peak Plasma Concentration of AZD6094 Following Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours
Time to Peak Plasma Concentration of AZD6094 After Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours
Apparent Volume of Distribution of AZD6094 Following Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours
Area Under Plasma Concentration Time Curve for AZD6094 After Single Dose (Time Zero to Last Measurement)
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours
Apparent Total Clearance of AZD6094 From Plasma After Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours
Mean Residence Time of AZD6094 After Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of evaluable PK parameters for this endpoint.
24 Hours
Elimination Half-Life of AZD6094 After Single Dose
Time Frame: 24 Hours
The number of patients analysed represent the number of patients with evaluable PK parameters for this endpoint.
24 Hours

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
AstraZeneca

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
SCRI Development Innovations, LLC

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Henrik-Tobias Arkenau, MD,PhD, Sarah Cannon Research Institute United Kingdom

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
April 30, 2014

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 14, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 20, 2020

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 23, 2014

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 28, 2014

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 1, 2014

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 19, 2021

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
March 23, 2021

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
March 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • D5082C00002
  • GU 111 (Other Identifier: Sarah Cannon Research Institute (SCRI))

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Time Frame

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA Pharma Data Sharing Principles. For details of our timelines, please rerefer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Access Criteria

When a request has been approved AstraZeneca will provide access to the de-identified individual patient-level data in an approved sponsored tool . Signed Data Sharing Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information. Additionally, all users will need to accept the terms and conditions of the SAS MSE to gain access. For additional details, please review the Disclosure Statements at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

IPD Sharing Supporting Information Type

  • STUDY_PROTOCOL
  • SAP

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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