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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT05061134




Registration number
NCT05061134
Ethics application status
Date submitted
22/09/2021
Date registered
29/09/2021

Titles & IDs
Public title
A Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Melanoma and Resistance to PD-(L)1 Inhibition
Scientific title
A Randomised, Open-Label, Phase 2 Study of Ceralasertib Monotherapy and Ceralasertib Plus Durvalumab in Patients With Unresectable or Advanced Melanoma and Primary or Secondary Resistance to PD-(L)1 Inhibition
Secondary ID [1] 0 0
2021-001722-21
Secondary ID [2] 0 0
D533AC00001
Universal Trial Number (UTN)
Trial acronym
MONETTE
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Melanoma 0 0
Condition category
Condition code
Cancer 0 0 0 0
Malignant melanoma

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Treatment: Drugs - Ceralasertib
Treatment: Other - Durvalumab

Experimental: Main study: Ceralasertib + Durvalumab - Participants will receive ceralasertib on Days 1 to 7 plus durvalumab Day 8, once in 28 days (Q28D), until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion is met.

Experimental: Main study: Ceralasertib - Participants will receive ceralasertib on Days 1 to 7, Q28D, until progressive disease, unacceptable toxicity, withdrawal of consent, or if a study treatment discontinuation criterion is met.

Experimental: Biopsy Sub-study: Ceralasertib + Durvalumab - From Cycle 1, participants will receive combination of ceralasertib twice daily (BD) Days 1 to 7 plus durvalumab Day 8, Q28D, until progressive disease, unacceptable toxicity, withdrawal of consent, or a study treatment discontinuation criterion is met.

Experimental: Biopsy study: Ceralasertib - During Cycle 0, participants will receive ceralasertib on Days 1 to 7, followed by an off-treatment period between Days 8 to 28.


Treatment: Drugs: Ceralasertib
Ceralasertib (240 mg) will be administered orally twice daily.

Treatment: Other: Durvalumab
Durvalumab (1500 mg) will be administered intravenously once every 28 days for participants who weight above \> 30 kgs. For participants who weigh below = 30 kgs, weight-based dosing equivalent to 20 mg/kg of durvalumab will be administered.

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

Outcomes
Primary outcome [1] 0 0
Main study: Objective response rate (ORR)
Timepoint [1] 0 0
8 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years)
Primary outcome [2] 0 0
Biopsy sub-study: CD8+ T-cells tumour infiltration assessed in baseline, on-treatment and off-treatment tumour biopsies
Timepoint [2] 0 0
Screening, on-treatment and off-treatment during Cycle 1
Secondary outcome [1] 0 0
Main study and Biopsy sub-study: Duration of Response (DoR)
Timepoint [1] 0 0
Main study: 8 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years); Biopsy study: 12 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years)
Secondary outcome [2] 0 0
Main study and Biopsy sub-study: Time to objective response (TTR)
Timepoint [2] 0 0
Main study: 8 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years); Biopsy study: 12 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years)
Secondary outcome [3] 0 0
Main study and Biopsy sub-study: Percentage change in target lesion tumour size
Timepoint [3] 0 0
Main study: 16 weeks; Biopsy study: 20 weeks
Secondary outcome [4] 0 0
Biopsy sub-study: ORR
Timepoint [4] 0 0
Biopsy study: 12 weeks after the start of treatment (Cycle 1 Day 1) until objective disease progression (approx 2 years)
Secondary outcome [5] 0 0
Main study and Biopsy sub-study: Progression free survival (PFS)
Timepoint [5] 0 0
From screening until objective disease progression or death (approx. up to 1 year)
Secondary outcome [6] 0 0
Main study and Biopsy sub-study: Overall survival (OS)
Timepoint [6] 0 0
From screening until death (approx. up to 2 years)
Secondary outcome [7] 0 0
Biopsy sub-study: Pre-treatment presence and/or on-treatment and/or off-treatment changes in PD-L1 and pRAD50
Timepoint [7] 0 0
Biopsy study: Screening, on-treatment and off-treatment during Cycle 1
Secondary outcome [8] 0 0
Main study and Biopsy sub-study: Number of adverse events and serious adverse events
Timepoint [8] 0 0
From screening until treatment discontinuation plus 90 day safety follow up (approx. up to 1 year)
Secondary outcome [9] 0 0
Main study: Concentration of ceralasertib in plasma
Timepoint [9] 0 0
Cycle 1, 2, 3 Day 7 (each cycle is 28 days)
Secondary outcome [10] 0 0
Biopsy sub-study: Assessment of proliferation of carcinoma in Ki67 marker (Marker Of Proliferation Ki-67) or CD8+ T cells immune cells
Timepoint [10] 0 0
From baseline, on-treatment and off-treatment until 24 months after the last patient (approx 2 years)

Eligibility
Key inclusion criteria
* Participants must have a histologically or cytologically confirmed diagnosis of unresectable or metastatic melanoma of cutaneous, acral or mucosal subtype
* Availability of an archival tumour sample and a fresh tumour biopsy taken at screening
* Patient must have received at least 1 prior immunotherapy (anti-PD-(L)1 ± anti-CTLA-4 [Cytotoxic T-lymphocyte-associated protein 4]) for a minimum of 6 weeks and no more than 2 prior regimens in the metastatic setting. Patients must have confirmed progression during treatment with a PD-(L)1 inhibitor +/- a CTLA-4 inhibitor.
* The interval between the last dose of anti-PD-(L)1, BRAF/MEK (B-Rapidly Accelerated Fibrosarcoma gene/mitogen-activated protein kinase gene) inhibitor and the first dose of the study regimen must be a minimum of 14 days
* Measurable disease by RECIST 1.1.
* Patients must have a life expectancy =3 months from proposed first dose date.
* Biopsy Sub-study: Consent to the provision of 3 mandatory tumour biopsies.
Minimum age
18 Years
Maximum age
130 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
* Patients must not have experienced a toxicity that led to permanent discontinuation of prior checkpoint inhibitors (CPI) treatment.
* History of another primary malignancy except for malignancy treated with curative intent with no known active disease = 3 years before the first dose of study treatment
* Uveal melanoma
* Must not have experienced a Grade = 3 immune-related AE or an immune-related neurologic or ocular AE of any grade while receiving prior immunotherapy
* History of symptomatic congestive heart failure, unstable angina pectoris, uncontrolled cardiac arrhythmia, which is symptomatic or requires treatment (CTCAE Grade 3), symptomatic or uncontrolled atrial fibrillation despite treatment, or asymptomatic sustained ventricular tachycardia. Patients with atrial fibrillation controlled by medication or arrhythmias controlled by pacemakers may be permitted upon discussion with the study clinical lead.
* History of organ transplant that requires use of immunosuppressive medications
* Inadequate bone marrow and impaired hepatic or renal function
* Known active infection requiring systemic therapy, active hepatitis infection, positive hepatitis C virus antibody, hepatitis B virus (HBV) surface antigen or HBV core antibody (anti-HBc), at screening
* Patients with confirmed COVID-19 infection by polymearse chain reaction test who have not made a full recovery.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
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
Parallel
Other design features
Phase
Phase 2
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 - East Melbourne
Recruitment hospital [2] 0 0
Research Site - Herston
Recruitment hospital [3] 0 0
Research Site - Woolloongabba
Recruitment postcode(s) [1] 0 0
3002 - East Melbourne
Recruitment postcode(s) [2] 0 0
4029 - Herston
Recruitment postcode(s) [3] 0 0
4102 - Woolloongabba
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
Florida
Country [3] 0 0
United States of America
State/province [3] 0 0
Maryland
Country [4] 0 0
United States of America
State/province [4] 0 0
Tennessee
Country [5] 0 0
Belgium
State/province [5] 0 0
Belgium
Country [6] 0 0
Belgium
State/province [6] 0 0
Bruges
Country [7] 0 0
Belgium
State/province [7] 0 0
Gent
Country [8] 0 0
Belgium
State/province [8] 0 0
Leuven
Country [9] 0 0
Canada
State/province [9] 0 0
Alberta
Country [10] 0 0
Canada
State/province [10] 0 0
Ontario
Country [11] 0 0
Canada
State/province [11] 0 0
Quebec
Country [12] 0 0
France
State/province [12] 0 0
Bobigny
Country [13] 0 0
France
State/province [13] 0 0
Boulogne Billancourt
Country [14] 0 0
France
State/province [14] 0 0
Marseille Cedex 5
Country [15] 0 0
France
State/province [15] 0 0
Paris
Country [16] 0 0
France
State/province [16] 0 0
Pau Cedex
Country [17] 0 0
France
State/province [17] 0 0
Pierre Benite Cedex
Country [18] 0 0
France
State/province [18] 0 0
Poitiers
Country [19] 0 0
France
State/province [19] 0 0
Vandoeuvre-Les-Nancy
Country [20] 0 0
France
State/province [20] 0 0
Villejuif Cedex
Country [21] 0 0
Germany
State/province [21] 0 0
Berlin
Country [22] 0 0
Germany
State/province [22] 0 0
Buxtehude
Country [23] 0 0
Germany
State/province [23] 0 0
Heidelberg
Country [24] 0 0
Germany
State/province [24] 0 0
Heilbronn
Country [25] 0 0
Germany
State/province [25] 0 0
Kiel
Country [26] 0 0
Germany
State/province [26] 0 0
Mainz
Country [27] 0 0
Germany
State/province [27] 0 0
München
Country [28] 0 0
Germany
State/province [28] 0 0
Regensburg
Country [29] 0 0
Germany
State/province [29] 0 0
Schwerin
Country [30] 0 0
Germany
State/province [30] 0 0
Tuebingen
Country [31] 0 0
Italy
State/province [31] 0 0
Candiolo
Country [32] 0 0
Italy
State/province [32] 0 0
Milan
Country [33] 0 0
Italy
State/province [33] 0 0
Napoli
Country [34] 0 0
Italy
State/province [34] 0 0
Padova
Country [35] 0 0
Italy
State/province [35] 0 0
Perugia
Country [36] 0 0
Italy
State/province [36] 0 0
Roma
Country [37] 0 0
Italy
State/province [37] 0 0
Siena
Country [38] 0 0
Korea, Republic of
State/province [38] 0 0
Goyang
Country [39] 0 0
Korea, Republic of
State/province [39] 0 0
Seoul
Country [40] 0 0
Poland
State/province [40] 0 0
Brzozów
Country [41] 0 0
Poland
State/province [41] 0 0
Gdansk
Country [42] 0 0
Poland
State/province [42] 0 0
Kraków
Country [43] 0 0
Poland
State/province [43] 0 0
Lodz
Country [44] 0 0
Poland
State/province [44] 0 0
Poznan
Country [45] 0 0
Poland
State/province [45] 0 0
Warszawa
Country [46] 0 0
Spain
State/province [46] 0 0
Barcelona
Country [47] 0 0
Spain
State/province [47] 0 0
Madrid
Country [48] 0 0
Spain
State/province [48] 0 0
Málaga
Country [49] 0 0
Spain
State/province [49] 0 0
Pamplona
Country [50] 0 0
Spain
State/province [50] 0 0
Pozuelo de Alarcon
Country [51] 0 0
United Kingdom
State/province [51] 0 0
Cambridge
Country [52] 0 0
United Kingdom
State/province [52] 0 0
Chelsea
Country [53] 0 0
United Kingdom
State/province [53] 0 0
Manchester
Country [54] 0 0
United Kingdom
State/province [54] 0 0
Northwood

Funding & Sponsors
Primary sponsor type
Commercial sector/industry
Name
AstraZeneca
Address
Country

Ethics approval
Ethics application status

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 0 0
Address 0 0
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

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
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 document/s available: Study protocol, Statistical analysis plan (SAP)
When will data be available (start and end dates)?
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.
Available to whom?
When a request has been approved AstraZeneca will provide access to the deidentified 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.
Available for what types of analyses?
How or where can data be obtained?
IPD available at link: https://astrazenecagroup-dt.pharmacm.com/DT/Home


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

No documents have been uploaded by study researchers.