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

NCT02127710 | Completed Phase 2 Results

• 2 other identifiers: D5082C00002GU 111
• Study Type: interventional
• Target: 111
• Locations: 4 countries
• Sites: 23

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.

Conditions

Papillary Renal Cell Cancer

Keywords

AZD6094; Savolitinib; Papillary Renal Cell Cancer

Outcome Measures

Primary Outcomes (3)

• Objective Response Rate (RECIST Version 1.1)

  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

  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

  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 Outcomes (15)

• Progression Free Survival Stratified by c-MET Status in the Efficacy Analysis Set

  Up to 12 months

• Overall Survival Stratified by c-MET Status in the Efficacy Analysis Set

  Up to 12 months

• 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

• Change From Baseline in Target Lesion Tumour Size at 12 Weeks in Efficacy Analysis Set

  12 Weeks (at 12 weeks timepoint)

Study Arms (1)

AZD6094 600 mg daily continuously

EXPERIMENTAL

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

Drug: AZD6094

Interventions

AZD6094 DRUG

AZD6094 is a potent and selective small molecule mesenchymal epithelial transition (c-MET) kinase inhibitor.

Also known as: Savolitinib, HMPL - 504

AZD6094 600 mg daily continuously

Eligibility Criteria

• Age: 18 Years - 99 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Provision of informed consent prior to any study specific procedures, sampling and analyses.
• Histologically confirmed PRCC, which is locally advanced or metastatic.
• Availability of an archival tumor sample or a pre-treatment fresh tumor sample for confirmation of PRCC by a central laboratory and other biomarker
• 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.
• Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1.
• 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.
• Adequate hematological function defined as:
• Absolute neutrophil count ≥1500/μL
• Haemoglobin ≥9 g/dL
• Platelets ≥100,000/μL
• Adequate liver function defined as:
• Alanine aminotransferase and aspartate aminotransferase ≤2.5 x the upper limit of normal (ULN)
• Total bilirubin ≤1.5 x ULN
• Adequate renal function defined as glomerular filtration rate ≥ 40 mL/min,
• Adequate coagulation parameters, defined as International Normalisation Ratio \<1.5 x ULN or activated partial thromboplastin time \<1.5 x ULN.

You may not qualify if:

• 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.
• 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.
• Prior or current treatment with a cMet inhibitor
• 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)
• 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
• Major surgical procedures ≤28 days of beginning study drug or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
• Previously untreated brain metastases.
• Current leptomeningeal metastases or spinal cord compression due to disease.
• Acute or chronic liver or pancreatic disease.
• Uncontrolled diabetes mellitus.
• Gastrointestinal disease or other condition that will interfere significantly with the absorption, distribution, metabolism, or excretion of oral therapy
• Any of the following cardiac diseases currently or within the last 6 months:
• Unstable angina pectoris
• Congestive heart failure (New York Heart Association ≥ Grade 2)
• Acute myocardial infarction

Sponsors & Collaborators

• AstraZeneca: lead
• SCRI Development Innovations, LLC: collaborator

Study Sites (23)

Research Site

Birmingham, Alabama, 35294, United States

Location

Research Site

Duarte, California, 91010, United States

Location

Research Site

Palo Alto, California, 94305, United States

Location

Research Site

Fort Myers, Florida, 33916, United States

Location

Research Site

Chicago, Illinois, 60637, United States

Location

Research Site

Iowa City, Iowa, 52242, United States

Location

Research Site

Boston, Massachusetts, 02215, United States

Location

Research Site

Detroit, Michigan, 48201, United States

Location

Research Site

New York, New York, 10021, United States

Location

Research Site

Philadelphia, Pennsylvania, 19111, United States

Location

Research Site

Nashville, Tennessee, 37203, United States

Location

Research Site

Dallas, Texas, 75246, United States

Location

Research Site

Houston, Texas, 77030, United States

Location

Research Site

Calgary, Alberta, T2N 4N2, Canada

Location

Research Site

Edmonton, Alberta, T6G 1Z2, Canada

Location

Research Site

Toronto, Ontario, M4N 3M5, Canada

Location

Research Site

Toronto, Ontario, M5G 2M9, Canada

Location

Research Site

Barcelona, 08041, Spain

Location

Research Site

Cambridge, CB2 0QQ, United Kingdom

Location

Research Site

Glasgow, G12 OYN, United Kingdom

Location

Research Site

London, EC1M 6BQ, United Kingdom

Location

Research Site

London, W1G 6AD, United Kingdom

Location

Research Site

Manchester, M20 4BX, United Kingdom

Location

Related Links

• D5082c00002-revised-csp-3\_Redacted

MeSH Terms

Conditions

Carcinoma, Renal Cell

Interventions

1-(1-(imidazo(1,2-a)pyridin-6-yl)ethyl)-6-(1-methyl-1H-pyrazol-4-yl)-1H-(1,2,3)triazolo(4,5-b)pyrazine

Condition Hierarchy (Ancestors)

Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms by Histologic Type; Neoplasms; Kidney Neoplasms; Urologic Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Kidney Diseases; Urologic Diseases; Male Urogenital Diseases

Limitations and Caveats

For the secondary outcome measure Duration of Response the median was not calculable because at data cut-off some participants were still responding. Point to note: All patients on this trial received 600mg AZD6094 po.

Results Point of Contact

• Title: Senior Medical Director, Savolitinib
• Organization: AstraZeneca

ClinicalTrialTransparency@astrazeneca.com

Study Officials

• Henrik-Tobias Arkenau, MD,PhD

  Sarah Cannon Research Institute United Kingdom

  STUDY CHAIR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 23, 2014
• First Posted: May 1, 2014
• Study Start: April 30, 2014
• Primary Completion: April 14, 2016
• Study Completion: April 20, 2020
• Last Updated: April 19, 2021
• Results First Posted: October 12, 2017

Record last verified: 2021-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• 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.
• 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.

Locations

GB (5); ES (1); CA (4); US (13)