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Brief Title: Sequential Combo Immuno and Target Therapy (SECOMBIT) Study
Official Title: A Three Arms Prospective, Randomized Phase II Study to Evaluate the Best Sequential Approach With Combo Immunotherapy (Ipilimumab/Nivolumab) and Combo Target Therapy (LGX818/MEK162) in Patients With Metastatic Melanoma and BRAF Mutation
Study ID: NCT02631447
Brief Summary: To evaluate the best sequencing approach with the combination of target agents (LGX818 plus MEK162) and the combination of immunomodulatory antibodies (ipilimumab plus nivolumab) in patients with metastatic melanoma and BRAF V600 mutation.
Detailed Description: The combination BRAF (B-raf murine sarcoma viral oncogene homolog B1) inhibitor plus mitogen-activated protein kinase (MEK) inhibitor seems to be more effective in the V600 BRAF mutated advanced melanoma patients compared to treatment with the BRAF inhibitors alone. In fact, a phase I-II study showed a better overall response rate (ORR) and progression-free survival (PFS) in the combination arm (dabrafenib plus trametinib) respect to the single agent treatment (dabrafenib): 76% and 9.4 months versus 54% and 5.8 months respectively. Another phase I study with a similar combination (vemurafenib plus cobimetinib) showed an ORR of 85% in vemurafenib-naïve patients. Recently, the results of a phase I study about the combination ipilimumab plus nivolumab have been reported. In this study at the selected schedule (ipilimumab 3 mg/kg and nivolumab 1 mg/kg), 53% of patients had an objective response, all with tumor reduction of 80% or more. Reponses were durable, although longer follow-up is needed. A recent phase I study has shown a high rate of liver toxicity with the combo ipilimumab plus vemurafenib . which makes difficult a combination with these two different drugs. Moreover, a better efficacy of the sequencing treatment BRAF inhibitors/ipilimumab vs. the single agent treatment was also observed; for this reason it was also suggested to start immunotherapy treatment in the BRAF V600 mutated melanoma population as first option, in order to increase the percentage of patients who can benefit from the sequencing, considering the possibility of a fast progression of the disease after the BRAF inhibitors treatment. Taking into account these considerations, it seems impossible to think to combine all the four compounds (the target agents and immunomodulating monoclonal antibodies). The risk of a high rate of toxicity is realistic and would render this approach inapplicable. Sequencing with these different combinations seems to be more feasible. However, also in this case it would be important to start with the best combination in order to give to the patients the best chance to increase the overall survival. The aim of this prospective randomized phase II study is to evaluate the sequencing of these two different combinations and evaluate which is the best of these approaches.
Minimum Age: 18 Years
Eligible Ages: ADULT, OLDER_ADULT
Sex: ALL
Healthy Volunteers: No
Paracelsus Medical University, Salzburg, AT, Austria
Karl Landsteiner University of Health Sciencies - University Clinic, St. Pölten, AT, Austria
Medical University of Graz, Graz, AU, Austria
Medical University of Vienna, Wien, , Austria
Hôpitaux Universitaires Saint-Louis, Paris, , France
University of Tuebingen, Tuebingen, , Germany
University of Athens, Athens, , Greece
IRCCS - Istituto Scientifico Romagnolo per la Cura e lo Studio dei Tumori (I.R.S.T) S.r.l., Meldola, Forlì-Cesena, Italy
National Institute of Cancer, Bari, , Italy
Università degli Studi di Bari Aldo Moro, Bari, , Italy
Azienda Ospedaliera Papa Giovanni XXIII, Bergamo, , Italy
IRCCS San Martino - IST, Genova, , Italy
Fondazione I.R.C.C.S. Istituto Nazionale dei Tumori, Milano, , Italy
IEO - Istituto Europeo di Oncologia - IRCCS, Milano, , Italy
Istituto Nazionale per lo Studio e la Cura dei Tumori "Fondazione Giovanni Pascale", Naples, , Italy
Azienda Ospedaliero Universitaria Federico II, Naples, , Italy
Istituto Oncologico Veneto, Padova, , Italy
Istituto Nazionale Tumori Regina Elena, Roma, , Italy
Istituto Dermopatico dell'Immacolata - IDI - IRCCS, Roma, , Italy
IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, , Italy
Azienda Ospedaliera Universitaria - Città della Salute e della Scienza di Torino, Torino, , Italy
Azienda Ospedaliera Universitaria Integrata di Udine, Udine, , Italy
Maria Sklodowska-Curie Institute - Oncology Center, Warsaw, PL, Poland
Hospital Universitario Quiròn Dexeus, Barcelona, SP, Spain
Hospital Clínic Barcelona, Barcelona, , Spain
Clinica Universidad de Navarra, Pamplona, , Spain
Karolinska University Hospital, Stockholm, , Sweden
University Hospital Zurich, Zurich, , Switzerland
The Royal Marsden NHS Foundation Trust, London, , United Kingdom
The Christie NHS Foundation Trust, Manchester, , United Kingdom
Name: Paolo Ascierto, MD
Affiliation: Fondazione Melanoma Onlus
Role: STUDY_CHAIR