CPDR001F2301 - Study on the safety and efficacy of PDR001 in combination with Dabrafenib and Trametinib in patients with advanced melanoma
Summary description of the study
This clinical study aims to evaluate whether treatment with PDR001 in combination with Dabrafenib (Tafinlar®) and Trametinib (Mekinist®) is safe and effective in patients with inoperable or metastatic melanoma. The study has three parts: • Part I "Safety Preliminary Study": This part aims to determine the optimal dosage and frequency of treatment with PDR001 as an addition to Dabrafenib and Trametinib in patients with melanoma. • Part II "Biomarker Study": This part focuses on the analysis of biomarkers in blood and tumor tissue to better characterize the impact of the study treatment on the immune system. • Part III "Randomized Main Study": Here, the efficacy of the combination of PDR001, Dabrafenib, and Trametinib is compared to the combination of placebo, Dabrafenib, and Trametinib. This part begins only after the Safety Preliminary Study is completed. Half of the patients will receive PDR001 & Dabrafenib & Trametinib, while the other half will receive a placebo (dummy medication) & Dabrafenib & Trametinib. Neither the patients nor the study physician know which of the two treatments is administered. If the interim analysis shows that the combination with PDR001 is effective, the protocol allows suitable patients to switch to the treatment arm with PDR001 instead of placebo.
(BASEC)
Intervention under investigation
The study includes 1 to 3 visits at the study center per treatment cycle (28 days) to monitor the health of study participants. The study drugs PDR001 or placebo are administered at the study center every four to eight weeks through a vein in the arm (intravenous infusion). Dabrafenib and Trametinib are capsules and tablets, respectively, that are taken once or twice daily.
(BASEC)
Disease under investigation
Patients with inoperable or metastatic BRAF-V600 mutated melanoma
(BASEC)
- Age >= 18 years - Previously untreated patients with inoperable or metastatic BRAF-V600 mutated melanoma (BASEC)
Exclusion criteria
- Patients with choroidal melanoma or mucosal melanoma - Patients with brain metastases - Patients with active autoimmune diseases (BASEC)
Trial sites
Aarau, Basel, Bern, Lausanne, Zurich
(BASEC)
Sponsor
Novartis Pharma Schweiz AG
(BASEC)
Contact
Contact Person Switzerland
Jutta Sommerfeld
+41 41 763 71 11
gmo.switzerland@clutternovartis.comNovartis Pharma Schweiz AG
(BASEC)
General Information
Novartis Pharmaceuticals
(ICTRP)
Scientific Information
Novartis Pharmaceuticals
(ICTRP)
Name of the authorising ethics committee (for multicentre studies, only the lead committee)
Ethics Committee Zurich
(BASEC)
Date of authorisation
16.02.2017
(BASEC)
ICTRP Trial ID
NCT02967692 (ICTRP)
Official title (approved by ethics committee)
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)
Academic 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 (ICTRP)
Public title
A Study of the Anti-PD1 Antibody PDR001, in Combination With Dabrafenib and Trametinib in Advanced Melanoma (ICTRP)
Disease under investigation
Melanoma (ICTRP)
Intervention under investigation
Biological: Spartalizumab;Other: Placebo;Drug: Dabrafenib;Drug: Trametinib (ICTRP)
Type of trial
Interventional (ICTRP)
Trial design
Allocation: Randomized. Intervention model: Parallel Assignment. Primary purpose: Treatment. Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor). (ICTRP)
Inclusion/Exclusion criteria
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)
not available
Primary and secondary end points
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)
Registration date
16.11.2016 (ICTRP)
Incorporation of the first participant
not available
Secondary sponsors
not available
Additional contacts
Novartis Pharmaceuticals, Novartis Pharmaceuticals (ICTRP)
Secondary trial IDs
2016-002794-35, CPDR001F2301 (ICTRP)
Results-Individual Participant Data (IPD)
not available
Further information on the trial
https://clinicaltrials.gov/ct2/show/NCT02967692 (ICTRP)
Results of the trial
Results summary
not available
Link to the results in the primary register
not available