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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/show/NCT04522323




Registration number
NCT04522323
Ethics application status
Date submitted
22/07/2020
Date registered
21/08/2020
Date last updated
28/04/2021

Titles & IDs
Public title
A Study to Evaluate MEDI5752 and Axitinib in Subjects With Advanced Renal Cell Carcinoma
Scientific title
A Phase 1b, Open-label Study to Evaluate the Safety, Tolerability, Pharmacokinetics, Immunogenicity, and Antitumor Activity of MEDI5752 in Combination With Axitinib in Subjects With Advanced Renal Cell Carcinoma
Secondary ID [1] 0 0
D7980C00003
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Advanced Renal Cell Carcinoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Non melanoma skin cancer
Cancer 0 0 0 0
Kidney

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Other interventions - MEDI5752
Treatment: Drugs - Axitinib

Experimental: Dose Exploration - The Dose exploration Phase will evaluate the safety and tolerability of MEDI5752 in combination with axitinib (27 patients)

Experimental: Dose Expansion - Evaluate safety and anti-tumor activity of MEDI5752 in combination with axitinib (50 pts)


Other interventions: MEDI5752
MEDI5752

Treatment: Drugs: Axitinib
INLYTA

Intervention code [1] 0 0
Other interventions
Intervention code [2] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Number of subjects experiencing advese events (AEs)/serious adverse events (SAEs) - The primary safety endpoint is as assessed by the number of subjects with adverse events and serious adverse events (SAEs) graded per NCI CTCAE v5.0.
Timepoint [1] 0 0
Informed consent through 90-Day Post Last Dose.
Primary outcome [2] 0 0
Number of Participants With Dose Limiting Toxicities (DLT) of MEDI5752 and Axitinib during the Dose Exploration period. - Determine the MTD or MAD of the combination of MEDI5752 and Axitinib. A dose limiting toxicities (DLT) is defined as MEDI-5752 treatment-related AE of any Grade 3 or higher toxicity (as defined in the protocol) CTCAE v5.0.
Timepoint [2] 0 0
Informed consent through the first 21 days of treatment with MEDI5752 and Axitnib in the Dose Exploration Period.
Primary outcome [3] 0 0
Number of subjects experiencing adverse events (AEs) leading to discontinuation. - The primary safety endpoint is as assessed by the number of subjects with serious adverse events (SAEs) graded per NCI CTCAE v5.0.
Timepoint [3] 0 0
Informed consent through 90-Day Post Last Dose.
Primary outcome [4] 0 0
Number of subjects experiencing abnormal laboratory evaluations. - The primary safety endpoint is as assessed by the number of subjects experiencing changes in laboratory evaluations from baseline.
Timepoint [4] 0 0
Informed Consent through 90 post treatment date.
Primary outcome [5] 0 0
Number of subjects experiencing changes in vital signs reported as Adverse Events. - The primary safety endpoint is assessed by the change in vital signs from baseline.
Timepoint [5] 0 0
Informed consent through 90-Day Post Last Dose
Primary outcome [6] 0 0
Number of subjects experiencing abnormal electrocardiograms (ECG) reported as Adverse Events. - The primary safety endpoint is as assessed by the change in ECG parameters from baseline.
Timepoint [6] 0 0
Informed consent through 90-Day Post Last Dose
Primary outcome [7] 0 0
Preliminary antitumor activity of MEDI5752 combined with axitinib by Objective response rate per RECIST version (v) 1.1. - The primary efficacy endpoint is assessed by the anti-tumor of MEDI5752 and Axitinib.
Timepoint [7] 0 0
First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
Secondary outcome [1] 0 0
Antitumor activity of MEDI5752 and axitinib by measuring the progression free survival (PFS) according to RECIST v1.1. - The endpoint for assessment of PFS is defined as the time from the first dose of treatment until the documentation of PD or death due to any cause, whichever occurs first.
Timepoint [1] 0 0
Last Subject Enrolled through study completion, an average of 48 months.
Secondary outcome [2] 0 0
Antitumor activity of MEDI5752 and axitinib by measuring the Best Overall Response (BOR) according to RECIST v1.1. - The endpoint for assessment of BOR will be based on all post-baseline disease assessments that occur prior to the initiation of subsequent anticancer treatment
Timepoint [2] 0 0
First subject enrolled through 18 months from last subject enrolled, an average of 30 months.
Secondary outcome [3] 0 0
Antitumor activity of MEDI5752 and axitinib by measuring the Disease Control Rate (DCR). - The endpoint for assessment of DCR is measured by the proportion of subjects with a BOR of confirmed CR, PR, or SD.
Timepoint [3] 0 0
Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [4] 0 0
Antitumor activity of MEDI5752 and axitinib by measuring the Duration of Response (DOR) according to RECIST v1.1. - The endpoint for assessment of DOR is measured by the duration from the first documented OR to the first documented PD or death due to any cause, whichever occurs first.
Timepoint [4] 0 0
Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [5] 0 0
Antitumor activity of MEDI5752 and axitinib by measuring the Time to Response (TTR) according to RECIST v1.1. - The endpoint for assessment of TTR is defined as the time from the first dose of treatment until the first documentation of an OR.
Timepoint [5] 0 0
Informed Consent through the date of first documented progression, end of study, date of death, or two years after last subject starts treatment whichever should occur first
Secondary outcome [6] 0 0
Pharmacokinetics of MEDI5752: Cmax - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Timepoint [6] 0 0
Day 1,8,15, 22,64 and then Day 1 of every other cycle
Secondary outcome [7] 0 0
Pharmacokinetics of MEDI5752: AUC - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Timepoint [7] 0 0
Day 1,8,15, 22,64 and then Day 1 of every other cycle
Secondary outcome [8] 0 0
Pharmacokinetics of MEDI5752: Cmin - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Timepoint [8] 0 0
Day 1,8,15, 22,64 and then Day 1 of every other cycle
Secondary outcome [9] 0 0
Pharmacokinetics of MEDI5752: t 1/2 - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Timepoint [9] 0 0
Day 1,8,15, 22,64 and then Day 1 of every other cycle
Secondary outcome [10] 0 0
Pharmacokinetics of MEDI5752: Clearance - The endpoints for the assessment of PK of MEDI5752 include individual MEDI5752 concentrations at different time points after administration.
Timepoint [10] 0 0
Day 1,8,15, 22,64 and then Day 1 of every other cycle
Secondary outcome [11] 0 0
Immunogencity of MEDI572: Incidence of ADAs against MEDI5752 - Immunogenicity of MEDI5752: The endpoints for the immunogenicity of MEDI5752 include the number of subjects who develop detectable anti-drug antibodies (ADAs) to MEDI5752.
Timepoint [11] 0 0
Day 1,8,15, 22,30,64 and then Day 1 of every other cycle

Eligibility
Key inclusion criteria
- Age = 18 at the time of screening

- Body weight > 35 kg

- Written informed consent

- Histologically or cytologically proven advanced RCC with clear cell component

- Advanced RCC not previously treated in that setting

- Provision of tumor material (= 5 unstained slides or tissue block) from an archival or
fresh tissue sample if clinically feasible

- ECOG performance status of 0 or 1

- Subjects must have at least 1 measurable lesion according to RECIST v1.1

- Life expectancy = 12 weeks

- Adequate organ and marrow function

- Female subjects of childbearing potential must have negative pregnancy test at
screening and prior to each administration of investigational product, and must use at
least one highly effective method of contraception.
Minimum age
18 Years
Maximum age
101 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
- Any condition that, in the opinion of the investigator, would interfere with
evaluation of the investigational product or interpretation of subject safety or study
results

- Concurrent enrollment in another clinical study, unless it is an observational study.

- Previous treatment with mTOR inhibitors, PD-1, PD-L1, or CTLA-4 inhibitors for RCC or
any other immune checkpoint inhibitors

- Previous treatment with axitinib; other VEGF TKIs used in the adjuvant setting are
allowed if last dose > 6 months prior to the first dose of investigational product

- History of active primary immunodeficiency:

- History of organ transplant

- Active or prior documented autoimmune or inflammatory disorders

- Current or prior use of immunosuppressive medication within 14 days prior to the first
dose of investigational product.

- Has poorly controlled hypertension defined as systolic BP = 140 mm Hg and/or diastolic
BP = 90 mm Hg.

- Thromboembolic (arterial or venous) events within previous 6 months

- Any concurrent therapy for cancer

- Receipt of live attenuated vaccine within 30 days prior to the first dose of
investigational product

- Known allergy or hypersensitivity to investigational product(s) or any of the
excipients of the investigational product(s)

- Untreated or progressive CNS metastatic disease, any leptomeningeal disease, or cord
compression

- History of another primary malignancy

- Unresolved toxicities from previous anticancer therapy

- Major surgery within 4 weeks prior to enrollment or radiation therapy within 2 weeks
prior to enrollment,

- Female subjects who are pregnant or breastfeeding as well as male or female subjects
of reproductive potential who are not willing to employ one highly effective method of
birth control as described in inclusion criteria

- History of arrhythmia which is symptomatic or requires treatment symptomatic or
uncontrolled atrial fibrillation despite treatment

- Uncontrolled intercurrent illness within the last 6 months prior to enrollment

- Clinically significant gastrointestinal abnormality

- Evidence of inadequate wound healing

- Current use or anticipated need for treatment with drugs or foods that are known
strong CYP3A4/5 inhibitors

Study design
Purpose of the study
Treatment
Allocation to intervention
N/A
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Single group
Other design features
Phase
Phase 1
Type of endpoint(s)
Statistical methods / analysis

Recruitment
Recruitment status
Active, not recruiting
Data analysis
Reason for early stopping/withdrawal
Other reasons
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
Recruitment hospital [1] 0 0
Research Site - Frankston
Recruitment hospital [2] 0 0
Research Site - Melbourne
Recruitment hospital [3] 0 0
Research Site - Waratah
Recruitment postcode(s) [1] 0 0
3199 - Frankston
Recruitment postcode(s) [2] 0 0
3000 - Melbourne
Recruitment postcode(s) [3] 0 0
2298 - Waratah
Recruitment outside Australia
Country [1] 0 0
United States of America
State/province [1] 0 0
California
Country [2] 0 0
United States of America
State/province [2] 0 0
District of Columbia
Country [3] 0 0
United States of America
State/province [3] 0 0
Florida
Country [4] 0 0
United States of America
State/province [4] 0 0
Missouri
Country [5] 0 0
United States of America
State/province [5] 0 0
New Jersey
Country [6] 0 0
United States of America
State/province [6] 0 0
New York
Country [7] 0 0
United States of America
State/province [7] 0 0
Ohio
Country [8] 0 0
United States of America
State/province [8] 0 0
Tennessee
Country [9] 0 0
France
State/province [9] 0 0
Villejuif Cedex
Country [10] 0 0
Spain
State/province [10] 0 0
Barcelona
Country [11] 0 0
Spain
State/province [11] 0 0
Córdoba
Country [12] 0 0
Spain
State/province [12] 0 0
Madrid
Country [13] 0 0
Spain
State/province [13] 0 0
Sabadell
Country [14] 0 0
Spain
State/province [14] 0 0
Sevilla
Country [15] 0 0
Spain
State/province [15] 0 0
Valencia

Funding & Sponsors
Primary sponsor type
Commercial sector/Industry
Name
MedImmune LLC
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
The purpose of this study is to evaluate MEDI5752 in combination with axitinib.in subjects
with advanced renal cell carcinoma.
Trial website
https://clinicaltrials.gov/show/NCT04522323
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
AstraZeneca Early Oncology
Address 0 0
AstraZeneca
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for public queries
Name 0 0
Address 0 0
Country 0 0
Phone 0 0
Fax 0 0
Email 0 0
Contact person for scientific queries

Summary results
Other publications