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Savolitinib vs. Sunitinib in MET-driven PRCC

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ClinicalTrials.gov Identifier: NCT03091192
Recruitment Status : Recruiting
First Posted : March 27, 2017
Last Update Posted : August 7, 2018
Sponsor:
Collaborator:
Hutchinson MediPharma (HMP)
Information provided by (Responsible Party):
AstraZeneca

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.

Condition or disease Intervention/treatment Phase
Carcinoma Carcinoma, Renal Cell Kidney Neoplasms Urologic Neoplasms Kidney Diseases Neoplasms by Site Enzyme Inhibitors Protein Kinase Inhibitors Drug: Savolitinib Drug: Sunitinib Phase 3

Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 180 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Official Title: 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)
Actual Study Start Date : July 25, 2017
Estimated Primary Completion Date : March 31, 2020
Estimated Study Completion Date : June 30, 2021


Arm Intervention/treatment
Experimental: Savolitinib
See: intervention description
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

Active Comparator: Sunitinib
See: intervention description
Drug: Sunitinib
50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off




Primary Outcome Measures :
  1. 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)


Secondary Outcome Measures :
  1. 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

  2. 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

  3. 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

  4. 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

  5. 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

  6. 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 ]
  7. 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 ]
  8. 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


Other Outcome Measures:
  1. 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 ]
  2. 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

  3. 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

  4. 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

  5. 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 ]
  6. 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

  7. 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

  8. 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 ]


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Ages Eligible for Study:   18 Years to 130 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03091192


Contacts
Contact: AstraZeneca Clinical Study Information Center 1-877-240-9479 information.center@astrazeneca.com
Contact: AstraZeneca Cancer Study Locator, CancerStudyLocator.com 877-400-4656 AstraZeneca@emergingmed.com

  Show 79 Study Locations
Sponsors and Collaborators
AstraZeneca
Hutchinson MediPharma (HMP)
Investigators
Principal Investigator: Toni K Choueiri, MD Dana-Farber Cancer Institute

Responsible Party: AstraZeneca
ClinicalTrials.gov Identifier: NCT03091192     History of Changes
Other Study ID Numbers: D5082C00003
First Posted: March 27, 2017    Key Record Dates
Last Update Posted: August 7, 2018
Last Verified: August 2018

Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No

Keywords provided by AstraZeneca:
Papillary Renal Cell Cancer
AZD6094
Savolitinib

Additional relevant MeSH terms:
Carcinoma
Neoplasms
Kidney Diseases
Carcinoma, Renal Cell
Neoplasms by Site
Kidney Neoplasms
Urologic Neoplasms
Neoplasms, Glandular and Epithelial
Neoplasms by Histologic Type
Urologic Diseases
Adenocarcinoma
Urogenital Neoplasms
Sunitinib
Antineoplastic Agents
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Physiological Effects of Drugs
Growth Inhibitors