Savolitinib vs. Sunitinib in MET-driven PRCC.
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| ClinicalTrials.gov Identifier: NCT03091192 |
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Recruitment Status :
Active, not recruiting
First Posted : March 27, 2017
Results First Posted : July 10, 2020
Last Update Posted : January 17, 2023
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Sponsor:
AstraZeneca
Collaborator:
Hutchinson MediPharma (HMP)
Information provided by (Responsible Party):
AstraZeneca
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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) |
| Actual Enrollment : | 60 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 |
| Actual Primary Completion Date : | August 18, 2019 |
| Estimated Study Completion Date : | December 29, 2023 |
Resource links provided by the National Library of Medicine
| Arm | Intervention/treatment |
|---|---|
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Experimental: Savolitinib
See: intervention description
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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 |
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Active Comparator: Sunitinib
See: intervention description
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Drug: Sunitinib
50 mg by mouth (PO) once daily (QD), with or w/o food, 4 weeks on/2weeks off |
Primary Outcome Measures :
- Progression Free Survival (PFS) by Blinded Independent Central Review (BICR) [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR. ]Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Progressive Disease (PD): >= 20% increase in the sum of diameters of TLs and an absolute increase in sum of diameters of >=5mm (compared to the previous minimum sum) or progression of NTLs or a new lesion. PFS is the time from date of randomisation until the date of PD (defined by Recist 1.1 and confirmed by BICR) or death (by any cause in the absence of progression) regardless of whether the patient withdrew from randomised therapy or received another anti-cancer therapy prior to progression.
Secondary Outcome Measures :
- Overall Survival (OS) [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR. ]Time between the date of randomisation and the date of death due to any cause.
- Objective Response Rate (ORR) by BICR [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR. ]Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. ORR is the percentage of patients with at least 1 visit response of CR or PR prior to progression or any further therapy.
- Duration of Response (DoR) by BICR [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR. ]Per Response Evaluation Criteria in Solid Tumours (RECIST v1.1) assessed by MRI or CT: Complete Response (CR): Disappearance of all target and non-target lesions and no new lesions; Partial Response (PR): >= 30% decrease in the sum of diameters of Target Lesions (compared to baseline) and no new lesions. DoR is the time from the date of first documented response until the date of documented progression or death in the absence of disease progression.
- Disease Control Rate (DCR) at 6 Months by BICR [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR. ]Disease control rate at 6 months is defined as the percentage of patients who have a best objective response of Complete Response or Partial Response in that period or who have demonstrated Stable Disease for a minimum interval of 23 weeks.
- Disease Control Rate (DCR) at 12 Months by BICR [ Time Frame: RECIST tumour assessments every 6 weeks from randomisation until disease progression as defined by Recist 1.1 and confirmed by BICR. ]Disease control rate at 12 months is defined as the percentage of patients who have a best objective response of complete responses or partial responses in that period or who have demonstrated stable disease for a minimum interval of 47 weeks.
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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:
- 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.
- 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
- 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
- Adequate haematological, renal, cardiac and liver functions
- Karnofsky performance status ≥ 80
Exclusion Criteria:
- 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.
- Prior treatment with a MET inhibitor (e.g. foretinib, crizotinib, cabozantinib, onartuzumab or previous savolitinib) or sunitinb.
- 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).
- Wide field radiotherapy administered ≤28 days or limited field radiation for palliation ≤7 days prior to the date of randomisation
- Major surgical procedures ≤28 days of randomisation or minor surgical procedures ≤7 days. No waiting is required following port-a-cath placement.
- Previously untreated brain metastases
- Serious active infection or gastrointestinal disease
- Presence of other active cancers, or history of treatment for invasive cancer within the last 5 years.
- 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
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
Locations
Show 59 study locations
Sponsors and Collaborators
AstraZeneca
Hutchinson MediPharma (HMP)
Investigators
| Principal Investigator: | Toni K Choueiri, MD | Dana-Farber Cancer Institute |
Study Documents (Full-Text)
Documents provided by AstraZeneca:
Documents provided by AstraZeneca:
Study Protocol [PDF] December 19, 2018
Statistical Analysis Plan [PDF] August 28, 2019
Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | AstraZeneca |
| ClinicalTrials.gov Identifier: | NCT03091192 |
| Other Study ID Numbers: |
D5082C00003 |
| First Posted: | March 27, 2017 Key Record Dates |
| Results First Posted: | July 10, 2020 |
| Last Update Posted: | January 17, 2023 |
| Last Verified: | January 2023 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Yes |
| Plan Description: | Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal. All request will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure. Yes, indicates that AZ are accepting requests for IPD, but this does not mean all requests will be shared. |
| Supporting Materials: |
Study Protocol Statistical Analysis Plan (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. |
| URL: | https://astrazenecagroup-dt.pharmacm.com/DT/Home |
| Studies a U.S. FDA-regulated Drug Product: | Yes |
| Studies a U.S. FDA-regulated Device Product: | No |
Keywords provided by AstraZeneca:
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Papillary Renal Cell Cancer AZD6094 Savolitinib |
Additional relevant MeSH terms:
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Carcinoma Neoplasms Carcinoma, Renal Cell Neoplasms by Site Kidney Neoplasms Urologic Neoplasms Kidney Diseases 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 Protein Kinase Inhibitors Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action |