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Trial details imported from ClinicalTrials.gov

For full trial details, please see the original record at https://clinicaltrials.gov/study/NCT02967692




Registration number
NCT02967692
Ethics application status
Date submitted
16/11/2016
Date registered
18/11/2016

Titles & IDs
Public title
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma
Scientific title
A Randomized, Double-blind, Placebo-controlled, Phase III Study Comparing the Combination of PDR001, Dabrafenib and Trametinib Versus Placebo, Dabrafenib and Trametinib in Previously Untreated Patients With Unresectable or Metastatic BRAF V600 Mutant Melanoma
Secondary ID [1] 0 0
2016-002794-35
Secondary ID [2] 0 0
CPDR001F2301
Universal Trial Number (UTN)
Trial acronym
COMBI-i
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: Other - Spartalizumab
Other interventions - Placebo
Treatment: Drugs - Dabrafenib
Treatment: Drugs - Trametinib

Experimental: Part 1: Safety run-in Cohort - In Part 1, participants are treated at different dose levels to determine the recommended Phase 3 regimen of spartalizumab in combination with dabrafenib and trametinib. The starting dose of spartalizumab is 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).

Experimental: Part 2: Biomarker cohort - In Part 2, participants are treated with spartalizumab 400 mg Q4W in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD).

Experimental: Part 3- Arm 1: Spartalizumab in combination with dabrafenib and trametinib - In Part 3, participants are randomized to receive spartalizumab at the RP3R identified in Part 1 (400 mg Q4W) in combination with approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)

Placebo comparator: Part 3- Arm 2: Placebo in combination with dabrafenib and trametinib - In Part 3, participants are randomized to receive matching placebo in combination with the approved dose of dabrafenib (150 mg BID) and trametinib (2 mg QD)


Treatment: Other: Spartalizumab
Spartalizumab powder for solution is used in Part 1 and Part 2, and as concentrate for solution for infusion for Part 3. Spartalizumab is administered via intravenous infusion over 30 minutes once every 4 weeks

Other interventions: Placebo
Placebo is administered via intravenous infusion over 30 minutes once every 4 weeks

Treatment: Drugs: Dabrafenib
Dabrafenib 150 mg capsules BID is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions.

Treatment: Drugs: Trametinib
Trametinib 2 mg tablets QD is administered orally for Days 1-28 of a 28-day cycle, in fasting conditions

Intervention code [1] 0 0
Treatment: Other
Intervention code [2] 0 0
Other interventions
Intervention code [3] 0 0
Treatment: Drugs
Comparator / control treatment
Control group

Outcomes
Primary outcome [1] 0 0
Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs)
Timepoint [1] 0 0
Up to 8 weeks (Part 1)
Primary outcome [2] 0 0
Biomarker Cohort (Part 2): Change From Baseline in Programmed Cell Death-ligand 1 (PD-L1) Expression Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib
Timepoint [2] 0 0
Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days
Primary outcome [3] 0 0
Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib
Timepoint [3] 0 0
Baseline, Cycle 1 Day 15 and Cycle 3 Day 1 (Part 2). Each cycle is 28 days
Primary outcome [4] 0 0
Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1
Timepoint [4] 0 0
Up to disease progression or death due to any cause, whichever occurs first, assessed up to 2.8 years (Part 3)
Secondary outcome [1] 0 0
Overall Survival (OS)
Timepoint [1] 0 0
Up to death due to any cause, assessed up to approximately 5 years
Secondary outcome [2] 0 0
Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1
Timepoint [2] 0 0
Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 years
Secondary outcome [3] 0 0
Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1
Timepoint [3] 0 0
From first documented response to date of first documented progression or death, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3)
Secondary outcome [4] 0 0
Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1
Timepoint [4] 0 0
Part 1: Up to 3.3 years. Part 2: Up to 3 years. Part 3: Up to 2.8 year
Secondary outcome [5] 0 0
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status Scores
Timepoint [5] 0 0
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Secondary outcome [6] 0 0
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Physical Functioning Scale Scores
Timepoint [6] 0 0
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Secondary outcome [7] 0 0
Randomized (Part 3): Change From Baseline in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Pain Symptom Scale Scores
Timepoint [7] 0 0
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Secondary outcome [8] 0 0
Randomized (Part 3): Time to 10 Point Definitive Deterioration in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ) C30- Global Health Status
Timepoint [8] 0 0
From baseline to date of at least 10 points relative to baseline worsening of the global health status score or death due to any cause, up to 2.8 years (Part 3)
Secondary outcome [9] 0 0
Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score
Timepoint [9] 0 0
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Secondary outcome [10] 0 0
Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score
Timepoint [10] 0 0
From baseline to 60 days post progression, assessed up to 2.8 years (Part 3)
Secondary outcome [11] 0 0
Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression
Timepoint [11] 0 0
Up to disease progression or death due to any cause, up to 2.8 years (Part 3)
Secondary outcome [12] 0 0
Randomized (Part 3): OS by PD-L1 Expression
Timepoint [12] 0 0
Up to death due to any cause, up to 5 years
Secondary outcome [13] 0 0
Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline
Timepoint [13] 0 0
Baseline
Secondary outcome [14] 0 0
Spartalizumab ADA Incidence
Timepoint [14] 0 0
Throughout study until 150 days after the last dose of spartalizumab, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3).
Secondary outcome [15] 0 0
Trough Concentration (Ctrough) for Spartalizumab
Timepoint [15] 0 0
Pre-infusion on Day 1 of each Cycle starting from Cycle 2, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days
Secondary outcome [16] 0 0
Pre-dose Plasma Concentration for Dabrafenib
Timepoint [16] 0 0
Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days
Secondary outcome [17] 0 0
Pre-dose Plasma Concentration for Trametinib
Timepoint [17] 0 0
Pre-infusion on Day 1 of every cycle from Cycle 2 to 12, and then every 6 cycles from Cycle 18 to 36, up to 3.3 years (Part 1), 3 years (Part 2) and 2.8 years (Part 3). Cycle=28 days
Secondary outcome [18] 0 0
Number of Participants With Dose Interruptions
Timepoint [18] 0 0
From baseline to end of treatment, up to 5 years
Secondary outcome [19] 0 0
Number of Participants With Dose Reductions
Timepoint [19] 0 0
From baseline to end of treatment, up to 5 years
Secondary outcome [20] 0 0
Relative Dose Intensity
Timepoint [20] 0 0
From baseline to end of treatment, up to 5 years

Eligibility
Key inclusion criteria
Inclusion criteria Part 1: Safety run-in

* Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
* Aspartate transaminase (AST) < 2.5× ULN and Alanine transaminase (ALT) < 2.5× ULN
* Measurable disease according to RECIST 1.1
* ECOG performance status = 1

Part 2: Biomarker cohort

* Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
* At least two cutaneous or subcutaneous or nodal lesions for tumor sample collection
* Measurable disease according to RECIST 1.1
* ECOG performance status = 2

Part 3: Double-blind, randomized, placebo-controlled part

* Histologically confirmed, unresectable or metastatic melanoma with BRAF V600 mutation
* ECOG performance status = 2
* Measurable disease according to RECIST 1.1
Minimum age
18 Years
Maximum age
No limit
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Part 1: Safety run-in

* Subjects with uveal or mucosal melanoma
* Any history of CNS metastases
* Prior systemic anti-cancer treatment for unresectable or metastatic melanoma
* Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollmen
* Radiation therapy within 4 weeks prior to start of study treatment
* Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment

Parts 2 & 3: Biomarker cohort & double-blind, randomized, placebo-controlled part

* Subjects with uveal or mucosal melanoma
* Prior systemic anti-cancer treatment for unresectable or metastatic melanoma
* Neoadjuvant and/or adjuvant therapy for melanoma completed less than 6 months prior to enrollment
* Radiation therapy within 4 weeks prior to start of study treatment
* Clinically active cerebral melanoma metastasis.
* Active autoimmune disease, and/or history of autoimmune disease(s) that required treatment

Other protocol-defined Inclusion/Exclusion may apply.

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
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Phase 3
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)
NSW,QLD,VIC,WA
Recruitment hospital [1] 0 0
Novartis Investigative Site - Gateshead
Recruitment hospital [2] 0 0
Novartis Investigative Site - North Sydney
Recruitment hospital [3] 0 0
Novartis Investigative Site - Greenslopes
Recruitment hospital [4] 0 0
Novartis Investigative Site - Prahran
Recruitment hospital [5] 0 0
Novartis Investigative Site - Nedlands
Recruitment postcode(s) [1] 0 0
2290 - Gateshead
Recruitment postcode(s) [2] 0 0
2060 - North Sydney
Recruitment postcode(s) [3] 0 0
4120 - Greenslopes
Recruitment postcode(s) [4] 0 0
3181 - Prahran
Recruitment postcode(s) [5] 0 0
6009 - Nedlands
Recruitment outside Australia
Country [1] 0 0
United States of America
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California
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United States of America
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Kansas
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United States of America
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Maryland
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United States of America
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Nebraska
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United States of America
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New York
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United States of America
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Pennsylvania
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United States of America
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Tennessee
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United States of America
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Texas
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United States of America
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Utah
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Argentina
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Buenos Aires
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Argentina
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Santa Fe
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Austria
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Tyrol
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Austria
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Graz
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Austria
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Linz
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Austria
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Salzburg
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Austria
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St Poelten
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Belgium
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Brussel
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Bruxelles
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PR
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Rio de Janeiro
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GE
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MI
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MO
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PD
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SI
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TO
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VR
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Napoli
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Breda
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Oslo
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Gdansk
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Portugal
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Lisboa
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Portugal
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Porto
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Chelyabinsk
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Moscow
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Nizhny Novgorod
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Omsk
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Saint Petersburg
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Samara
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St Petersburg
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Andalucia
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Asturias
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Cadiz
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Catalunya
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Spain
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Comunidad Valenciana
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Spain
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Galicia
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Spain
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Las Palmas de Gran Canaria
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Spain
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Madrid
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Sweden
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Goteborg
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Sweden
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Lund
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Sweden
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Stockholm
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Switzerland
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Aarau
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Switzerland
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Zuerich
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Thailand
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Hat Yai
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Thailand
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Bangkok
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United Kingdom
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Cornwall
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United Kingdom
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England
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United Kingdom
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Middlesex
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United Kingdom
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Surrey
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United Kingdom
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Leicester
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United Kingdom
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London
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United Kingdom
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Manchester
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United Kingdom
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Middlesbrough
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United Kingdom
State/province [154] 0 0
Preston

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

Ethics approval
Ethics application status

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

Contacts
Principal investigator
Name 0 0
Novartis Pharmaceuticals
Address 0 0
Novartis Pharmaceuticals
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?
Novartis is committed to sharing with qualified external researchers, access to patient-level data and supporting clinical documents from eligible studies. These requests are reviewed and approved by an independent review panel on the basis of scientific merit. All data provided is anonymized to respect the privacy of patients who have participated in the trial in line with applicable laws and regulations.

This trial data availability is according to the criteria and process described on www.clinicalstudydatarequest.com
When will data be available (start and end dates)?
Available to whom?
Available for what types of analyses?
How or where can data be obtained?


What supporting documents are/will be available?

Results publications and other study-related documents

No documents have been uploaded by study researchers.