Savolitinib vs. Sunitinib in MET-driven PRCC.
Condition: Carcinoma; Carcinoma, Renal Cell; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases; Neoplasms by Site; Enzyme Inhibitors; Protein Kinase Inhibitors
MeSH terms: Carcinoma; Neoplasms; Carcinoma, Renal Cell; Neoplasms by Site; Kidney Neoplasms; Urologic Neoplasms; Kidney Diseases
Intervention: Savolitinib; Sunitinib
Intervention description: 600 mg (400 mg if <50 kg) by mouth (PO) with a meal once daily (QD), continuously; 50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off
Intervention MeSH terms: Sunitinib
Phase: Phase 3
Study type: Interventional
Primary purpose: Treatment
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: None (Open Label)
Enrollment: 60.0
Sex: All
Minimum age: 18 Years
Maximum age: 130 Years
Healthy volunteers: No
Keywords: Papillary Renal Cell Cancer; AZD6094; Savolitinib

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.
    

Eligibility 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.

          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