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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
Results First Posted : July 10, 2020
Last Update Posted : August 11, 2020
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

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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 31, 2020


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) 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 :
  1. 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.

  2. 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.

  3. 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.

  4. 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.

  5. 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.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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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.
  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

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 Show 58 study locations
Sponsors and Collaborators
AstraZeneca
Hutchinson MediPharma (HMP)
Investigators
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Principal Investigator: Toni K Choueiri, MD Dana-Farber Cancer Institute
  Study Documents (Full-Text)

Documents provided by AstraZeneca:
Statistical Analysis Plan  [PDF] August 28, 2019
Study Protocol  [PDF] December 19, 2018

Additional Information:
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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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: August 11, 2020
Last Verified: July 2020
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.
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

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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:
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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