CPDR001F2301 - Study on the safety and efficacy of PDR001 in combination with Dabrafenib and Trametinib in patients with advanced melanoma

Argentina, Australia, Austria, Belgium, Brazil, Bulgaria, Canada, Chile, Czechia, Denmark, France, Germany, Greece, Hungary, Israel, Italy, Japan, Mexico, Netherlands, Norway, Poland, Portugal, Russian Federation, Spain, Sweden, Switzerland, Thailand, United Kingdom, United States (ICTRP)

ICTRP Studien-ID
NCT02967692 (ICTRP)

Offizieller Titel (Genehmigt von der Ethikkommission)
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 (BASEC)

Wissenschaftlicher Titel
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 (ICTRP)

Öffentlicher Titel
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma (ICTRP)

Untersuchte Krankheit(en)
Melanoma (ICTRP)

Untersuchte Intervention
Biological: Spartalizumab;Other: Placebo;Drug: Dabrafenib;Drug: Trametinib (ICTRP)

Studientyp
Interventional (ICTRP)

Studiendesign
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)

Ein-/Ausschlusskriterien
Gender: All
Maximum age: 100 Years
Minimum age: 18 Years
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

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. (ICTRP)

nicht verfügbar

Primäre und sekundäre Endpunkte
Safety Run-In (Part 1): Number of Participants With Dose Limiting Toxicities (DLTs);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;Biomarker Cohort (Part 2): Change From Baseline in CD8+ Cells Upon Treatment With Spartalizumab in Combination With Dabrafenib and Trametinib;Randomized (Part 3): Progression-Free Survival (PFS) as Per Investigator's Assessment by RECIST 1.1 (ICTRP)

Overall Survival (OS);Overall Response Rate (ORR) as Per Investigator's Assessment by RECIST 1.1;Duration of Response (DOR) as Per Investigator's Assessment by RECIST 1.1;Disease Control Rate (DCR) as Per Investigator's Assessment by RECIST 1.1;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;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;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;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;Randomized (Part 3): Change From Baseline in Function Assessment Cancer Therapy-melanoma (FACT-M) Melanoma Subscale Score;Randomized (Part 3): Change From Baseline in EuroQoL 5-level Instrument (EQ-5D-5L)- Visual Analog Scale (VAS) Score;Randomized (Part 3): PFS as Per Investigator's Assessment by RECIST 1.1 by PD-L1 Expression;Randomized (Part 3): OS by PD-L1 Expression;Spartalizumab Anti-drug Antibody (ADA) Prevalence at Baseline;Spartalizumab ADA Incidence;Trough Concentration (Ctrough) for Spartalizumab;Pre-dose Plasma Concentration for Dabrafenib;Pre-dose Plasma Concentration for Trametinib;Number of Participants With Dose Interruptions;Number of Participants With Dose Reductions;Relative Dose Intensity (ICTRP)

Registrierungsdatum
16.11.2016 (ICTRP)

Einschluss des ersten Teilnehmers
nicht verfügbar

Sekundäre Sponsoren
nicht verfügbar

Weitere Kontakte
Novartis Pharmaceuticals, Novartis Pharmaceuticals (ICTRP)

Sekundäre IDs
2016-002794-35, CPDR001F2301 (ICTRP)

Angaben zur Verfügbarkeit von individuellen Teilnehmerdaten
nicht verfügbar

Weitere Informationen zur Studie
https://clinicaltrials.gov/ct2/show/NCT02967692 (ICTRP)