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Savolitinib vs. Sunitinib in MET-driven PRCC

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT03091192
Recruitment Status : Active, not recruiting
First Posted : March 27, 2017
Last Update Posted : March 13, 2020
Sponsor:
Collaborator:
Hutchinson MediPharma (HMP)
Information provided by (Responsible Party):
AstraZeneca

Tracking Information
First Submitted Date  ICMJE February 9, 2017
First Posted Date  ICMJE March 27, 2017
Last Update Posted Date March 13, 2020
Actual Study Start Date  ICMJE July 25, 2017
Actual Primary Completion Date August 18, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
Progression Free Survival (PFS) [ Time Frame: Up to approximately 32 months after 1st patient randomized (121 PFS occurrences) ]
Time from randomisation to progression or death (PFS)
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: March 21, 2017)
  • Overall Survival (OS) [ Time Frame: Up to approximately 47 months after 1st patient randomized (121 OS occurrences) ]
    Time from the date of a patient's randomisation until death due to any cause
  • Objective Response Rate (ORR) [ Time Frame: Up to approximately 32 months after 1st patient randomized (at the time of PFS analysis) ]
    The proportion of patients achieving a complete or partial tumour response according to RECIST 1.1 criteria
  • Duration of Response (DoR) [ Time Frame: Up to approximately 32 months after 1st patient randomized (at the time of PFS analysis) ]
    The time from first documented tumour response until the date of documented progression or death from any casue
  • Disease Control Rate (DCR) [ Time Frame: At 6 and 12 months following the date of randomisation ]
    The proportion of patients achieving a complete response or partial response or stable disease according to RECIST 1.1 criteria
  • The plasma concentration-time data will be analysed by non-linear mixed effects modelling in order to evaluate the pharmacokinetic characteristics of savolitinib [ Time Frame: Cycle 1 Day 1 - pre-dose; Cycle 1 Day 15 - pre-dose and 1 and 3 hours post-dose; Cycle 1 Day 29 - pre-dose; Cycle 2 Day 15 - pre-dose ]
    Blood samples will be collected at various timepoints from patients receiving savolitinib
  • Mean change from baseline in FKSI-19 (Cancer Therapy Kidney Symptom Index-19) score [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, or end of treatment, whichever came first, assessed up to approximately 32 months ]
  • Mean change from baseline in FACIT-F (Functional Assessment of Chronic Illness Therapy - Fatigue) score [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, or end of treatment, whichever came first, assessed up to approximately 32 months ]
  • Best percentage change in tumour size [ Time Frame: Up to approximately 32 months after 1st patient randomized (at the time of PFS analysis) ]
    The maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction according to RECIST 1.1 criteria
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures
 (submitted: March 21, 2017)
  • Collection of adverse events (AEs) and serious adverse events (SAEs) as characterized and graded by National Cancer Institute (NCI) Common Terminology Criteria for Adverse Event [CTCAE] v4.03 [ Time Frame: Continuously from a patient randomization to 30 (+/-7) days after discontinuation of study drug ]
  • Collection of PRO CTCAE (The Patient-Reported Outcomes version of the Common Terminology Criteria) symptoms [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, or end of treatment, whichever came first, assessed up to approximately 32 months ]
    To assess the impact of savolitinib vs. sunitinib on patient reported AEs
  • Progression Fress Survival 2 (PFS2) [ Time Frame: Time from the patient randomization to data cut off (approx. 48 months) ]
    Time from randomisation to second progression or death; Following centrally confirmed progression and discontinuation of study drug, patients not continuing on post-progression study treatment will continue to be followed at least every 12 weeks by the site personnel for second PFS
  • Hospitalisations [ Time Frame: Continously from Day 1 Cycle 1 to 30 (+/-7) days after discontinuation of study drug ]
    All visits up to progression or end of treatment visit
  • Health state response and utility index derived from the EQ-5D-5L (European Quality of Life-5 Dimensions-5 Levels) questionnaire [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, or end of treatment, whichever came first, assessed up to approximately 32 months ]
  • Correlation of polymorphisms with variation in Pharmacokinetics, Pharmacodynamics, safety, response or disease observed in patients treated with savolitinib [ Time Frame: Once at Day 1 Cycle 1 ]
    Collect and store deoxyribonucleic acid (DNA) for future exploratory research into genes/genetic variation that may influence PK or response to savolitinib (i.e., absorption, distribution, metabolism, excretion, safety and efficacy) and/or susceptibility to/development of cancers
  • Comparison of MET-driven status between tumour DNA and plasma derived ctDNA [ Time Frame: At baseline ]
    To compare the MET-driven status of the tumour with results from plasma ctDNA testing in all screened patients
  • Number of participants with abnormal laboratory values (change from baseline) [ Time Frame: From date of randomization until the date of first documented progression, date of death from any cause, or end of treatment, whichever came first, assessed up to approximately 33 months ]
Original Other Pre-specified Outcome Measures Same as current
 
Descriptive Information
Brief Title  ICMJE Savolitinib vs. Sunitinib in MET-driven PRCC
Official Title  ICMJE A Phase III, Open Label, Randomised, Controlled, Multi-Centre Study To Assess the Efficacy and Safety of Savolitinib Versus Sunitinib in Patients With MET-Driven, Unresectable and Locally Advanced, Or Metastatic Papillary Renal Cell Carcinoma (PRCC)
Brief Summary This study is designed for patients diagnosed with MET-driven, unresectable and locally advanced or metastatic Papillary Renal Cell Carcinoma. The purpose of this study is to see if an investigational new anti-cancer medication, savolitinib, is effective in treating patients with MET-driven PRCC, how it compares with another medication frequently used to treat this disease called sunitinib, and what side effects it might cause.
Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Carcinoma
  • Carcinoma, Renal Cell
  • Kidney Neoplasms
  • Urologic Neoplasms
  • Kidney Diseases
  • Neoplasms by Site
  • Enzyme Inhibitors
  • Protein Kinase Inhibitors
Intervention  ICMJE
  • Drug: Savolitinib
    600 mg (400 mg if <50 kg) by mouth (PO) with a meal once daily (QD), continuously
    Other Name: AZD6094 (HMPL-504)/Volitinib
  • Drug: Sunitinib
    50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off
Study Arms  ICMJE
  • Experimental: Savolitinib
    See: intervention description
    Intervention: Drug: Savolitinib
  • Active Comparator: Sunitinib
    See: intervention description
    Intervention: Drug: Sunitinib
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Actual Enrollment  ICMJE
 (submitted: January 17, 2019)
60
Original Estimated Enrollment  ICMJE
 (submitted: March 21, 2017)
180
Estimated Study Completion Date  ICMJE December 31, 2020
Actual Primary Completion Date August 18, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

Inclusion Criteria:

  1. Histologically confirmed PRCC, which is unresectable/locally advanced or metastatic with measurable disease as per RECIST 1.1. Patients with papillary urothelial carcinoma or renal pelvis cancer of the kidney are not considered PRCC and are not eligible.
  2. Confirmation of MET-driven PRCC without co-occurring FH or VHL mutations from an FFPE tumour sample using the sponsor-designated central laboratory validated NGS assay
  3. Patients who have received no prior systemic therapy as well as those who have received prior systemic therapy for PRCC in the advanced setting.* Patients can be treatment-naïve, or previously treated, but cannot have previously received sunitinib or a MET inhibitor. Patients who have received prior systemic therapy must have had disease progression in soft tissue disease or bone within 6 months of the last dose of the most recent systemic therapy
  4. Adequate haematological, renal, cardiac and liver functions
  5. Karnofsky performance status ≥ 80

Exclusion Criteria:

  1. Most recent cytotoxic chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents <28 days from the date of randomisation. Most recent non cytotoxic targeted therapy <14 days from the date of randomisation.
  2. Prior treatment with a MET inhibitor (e.g. foretinib, crizotinib, cabozantinib, onartuzumab or previous savolitinib) or sunitinb.
  3. Treatment with strong inducers or inhibitors of CYP3A4 or strong inhibitors of CYP1A2, taken within 2 weeks or not possible to be stopped for at least 2 week before the date of randomisation. Herbal medications cannot be taken within 7 days of the date of randomisation (3 weeks for St John's wort).
  4. Wide field radiotherapy administered ≤28 days or limited field radiation for palliation ≤7 days prior to the date of randomisation
  5. Major surgical procedures ≤28 days of randomisation or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
  6. Previously untreated brain metastases
  7. Serious active infection or gastrointestinal disease
  8. Presence of other active cancers, or history of treatment for invasive cancer within the last 5 years.
  9. Mean resting QTcF >470 msec for women and >450 msec for men on the Part 2 screening triplicate ECGs or factors that may increase the risk of QTcF prolongation such as chronic hypokalaemia not correctable with supplements, congenital or familial long QT syndrome, or family history of unexplained sudden death under 40 years of age in first-degree relatives or any concomitant medication known to prolong the QT interval and cause Torsades de Pointes
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 130 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Brazil,   France,   Italy,   Korea, Republic of,   Russian Federation,   Ukraine,   United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03091192
Other Study ID Numbers  ICMJE D5082C00003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE Not Provided
Responsible Party AstraZeneca
Study Sponsor  ICMJE AstraZeneca
Collaborators  ICMJE Hutchinson MediPharma (HMP)
Investigators  ICMJE
Principal Investigator: Toni K Choueiri, MD Dana-Farber Cancer Institute
PRS Account AstraZeneca
Verification Date March 2020

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP