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.
Active, not recruiting
Phase 3
| Drug | Synonyms | Arms |
|---|---|---|
| Savolitinib | AZD6094 (HMPL-504)/Volitinib | Savolitinib |
| Sunitinib | Sunitinib |
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.
| Name | Type | Description | Interventions |
|---|---|---|---|
| Savolitinib | Experimental | See: intervention description |
|
| Sunitinib | Active Comparator | See: intervention description |
|
Inclusion Criteria:
1. Histologically confirmed Papillary Renal Cell Carcinoma, which is unresectable and locally advanced or metastatic with measurable disease as per RECIST 1.1.
2. Confirmation of MET-driven PRCC without co-occurring Fumarate Hydratase or Von Hippel Lindau mutations from a tumour sample using the sponsor-designated central laboratory validated MET Next Generational Sequencing assay
3. Patients who have received no prior systemic therapy as well as those who have received prior systemic therapy for PRCC. Patients who have received prior therapy must have had disease progression within 6 months of the last dose of previous systemic therapy
4. Adequate haematological, renal (creatinine < 2xULN), cardiac and liver functions
5. Karnofsky performance status ≥ 80
6. Ability to swallow oral medicines.
Exclusion Criteria:
1. Most recent cytotoxic chemotherapy, immunotherapy, chemo-immunotherapy, or investigational agents <21 days from the date of randomisation or 5 half-lives of the agent, whichever is longer. 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 weeks before the date of randomisation.
4. History of serious liver disease
5. Serious active infection or gastrointestinal disease
6. Uncontrolled hypertension (BP ≥150/95 mmHg despite medical therapy)
| Maximum Eligible Age: | 130 Years |
| Minimum Eligible Age: | 18 Years |
| Eligible Gender: | All |
| Healthy Volunteers: | No |
| Measure: | Progression Free Survival (PFS) |
| Time Frame: | Up to approximately 32 months after 1st patient randomized (121 PFS occurrences) |
| Safety Issue: | |
| Description: | Time from randomisation to progression or death (PFS) |
| Measure: | Overall Survival (OS) |
| Time Frame: | Up to approximately 47 months after 1st patient randomized (121 OS occurrences) |
| Safety Issue: | |
| Description: | Time from the date of a patient's randomisation until death due to any cause |
| Measure: | Objective Response Rate (ORR) |
| Time Frame: | Up to approximately 32 months after 1st patient randomized (at the time of PFS analysis) |
| Safety Issue: | |
| Description: | The proportion of patients achieving a complete or partial tumour response according to RECIST 1.1 criteria |
| Measure: | Duration of Response (DoR) |
| Time Frame: | Up to approximately 32 months after 1st patient randomized (at the time of PFS analysis) |
| Safety Issue: | |
| Description: | The time from first documented tumour response until the date of documented progression or death from any casue |
| Measure: | Disease Control Rate (DCR) |
| Time Frame: | At 6 and 12 months following the date of randomisation |
| Safety Issue: | |
| Description: | The proportion of patients achieving a complete response or partial response or stable disease according to RECIST 1.1 criteria |
| Measure: | 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 |
| Safety Issue: | |
| Description: | Blood samples will be collected at various timepoints from patients receiving savolitinib |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Measure: | 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 |
| Safety Issue: | |
| Description: |
| Measure: | Best percentage change in tumour size |
| Time Frame: | Up to approximately 32 months after 1st patient randomized (at the time of PFS analysis) |
| Safety Issue: | |
| Description: | The maximum reduction from baseline or the minimum increase from baseline in the absence of a reduction according to RECIST 1.1 criteria |
| Phase: | Phase 3 |
| Primary Purpose: | Interventional |
| Overall Status: | Not yet recruiting |
| Lead Sponsor: | AstraZeneca |
March 21, 2017
