Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Symptoms and General Pathology

Rare Diseases

Melanoma

Disease Progression

Neuroendocrine Tumors

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Nerve Tissue

Nevus, Pigmented

Nevus

Nevi and Melanomas

Skin Neoplasms

Skin Diseases

Disease Attributes

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Pembrolizumab

Nivolumab

Vemurafenib

Antineoplastic Agents, Immunological

Immune Checkpoint Inhibitors

Local treatment (i.e. surgery, radiotherapy) + Vemurafenib 240mg tablets (4 tabs/twice daily for 28 consecutive days) + Cobimetinib 20mg tablets (3 tabs/day for 21 consecutive days) beyond focal progression.

Pembrolizumab daily dose 2 mg/kg milligram(s)/kilogram or Nivolumab daily dose 3 mg/kg milligram(s)/kilogram.

Vemurafenib is taken on a 28-day cycle. Each dose consists of four 240 mg (960 mg) tablets twice daily for 28 consecutive days. The first dose should be taken in the morning and the second dose in the evening approximately 12 hours later. Each dose can be taken with or without a meal. Vemurafenib tablets should be swallowed whole with a glass of water and should not be chewed or crushed.

Cobimetinib is taken on a 28-day cycle. Each dose consists of three 20 mg tablets (60 mg) and should be taken orally, once daily for 21 consecutive days, followed by a 7-day break. Each subsequent treatment cycle should start after the 7-day treatment break has elapsed. The dose should be taken in the morning.

Local treatment (i.e. surgery, radiotherapy).

Experimental combination beyond Focal Progression

Pembrolizumab 2 mg/kg is administered as an intravenous infusion over 30 minutes every 3 weeks OR Nivolumab 3 mg/kg is administered intravenously over 60 minutes every 2 weeks.

Pembrolizumab or Nivolumab

Paola Queirolo, Dr.

The purpose of this study is to evaluate the efficacy beyond progression of vemurafenib combined with cobimetinib associated with local treatment compared to second-line treatment in patients with BRAFV600 mutation-positive metastatic melanoma in focal progression with first-line combined vemurafenib and cobimetinib.

Melanoma is a heterogeneous skin tumor, characterized by mutations of different oncogenes. Almost half of patients with advanced melanoma have a gene mutation of BRAF serine-threonine kinase. Over the past 5 years, two BRAF inhibitors targeting these mutations, vemurafenib and dabrafenib, have shown high rates of rapid response in phase II and III studies. However, the duration of responses is limited in most patients due to the development of acquired resistance. Mechanisms of resistance to BRAF inhibitor therapy are diverse and include the reactivation of the mitogen-activated protein kinase (MAPK) pathway in over two-thirds of tumors, along with promotion of parallel signaling networks.

Recently, the combination of drugs was superior in terms of responses, Progression Free Survival (PFS) and Overall Survival (OS) compared to monotherapy.

The data from recent studies confirm the clinical benefit of the combination of Vemurafenib with cobimetinib and support the use of the combination as a standard first-line approach to improve survival in patients.

The aim of this randomized, open-label, phase II study is to evaluate the efficacy, in terms of overall survival, of vemurafenib combined with cobimetinib associated with local treatment compared with second-line therapy, in patients with BRAFV600 mutation-positive metastatic melanoma in focal progression with first-line combined vemurafenib and cobimetinib.

To Evaluate the Efficacy Beyond Progression of Vemurafenib+Cobimetinib Associated With Local Treatment Compared to Second-line Treatment in Patients With BRAFV600+ Metastatic Melanoma in Focal Progression With First-line+Vemurafenib+Cobimetinib.

An Evaluation of the Efficacy Beyond Progression of Vemurafenib Combined With Cobimetinib Associated With Local Treatment Compared to Second-line Treatment in Patients With BRAFV600 Mutation-positive Metastatic Melanoma in Focal Progression With First-line Combined Vemurafenib and Cobimetinib.

Overall survival of patients with focal progression is defined as the time, in months, from randomization to the date of death from any cause. If a patient is not known to have died, survival time will be censored at the date of last contact ("last known date alive"). Overall survival of patients with focal progression will be compared between treatment groups using a log-rank test procedure with a two-sided α =0.2 level. The OS function for each treatment group will be estimated using the Kaplan-Meier product-limit method. Median and corresponding two-sided 80% confidence intervals will be computed by treatment group. A Cox proportional hazard model for OS with treatment arm as single factor will be used to estimate the hazard ratio of vemurafenib and cobimetinib plus local treatment to Standard of Care (SOC) second-line treatment and its corresponding 80% confidence interval.

PFS of patients with focal progression is defined as the time, in months, from randomization to the date of the first documented tumor progression or death due to any cause, whichever comes first. Clinical deterioration will not be considered progression. For subjects who neither progress nor die, time will be censored at the date of their last tumor assessment. For subjects who start a new anti-tumor treatment, time will be censored at the start of the new treatment. For a randomized subject who does not have any post-randomization tumor assessments and who has not died, time will be censored at the randomization date. PFS will be compared between treatment groups using a log-rank test procedure with a two-sided α =0.2 level. The PFS function for each treatment group will be estimated using the Kaplan-Meier product-limit method. Median and two-sided 80% confidence intervals (CI) for median PFS will be computed by treatment group. A Cox proportional hazard model for PFS with treatment

Overall survival of patients with non-focal progression is defined as the time, in months, from date of non-focal progression to first-line to the date of death from any cause. If a patient is not known to have died, survival time will be censored at the date of last contact ("last known date alive"). The OS function will be estimated using the Kaplan-Meier product-limit method. Median and corresponding two-sided 80% confidence intervals will be computed. Overall survival results of patients with non-focal progression will be descriptively compared with OS results of patients with focal progression (i.e. primary efficacy endpoint).

Overall survival results of patients with non-focal progression will be descriptively compared with OS results of patients with focal progression (i.e. primary efficacy endpoint). No statistical test will be foreseen for this comparison. The overall survival results are defined as the time, in months, from the date of progression to the date of death.

Nature of adverse events (AE) and serious adverse events (SAE) verified during the study. Safety analyses will be reported by actual treatment group and on the Non-focal Progression Set. AE and SAE will be assessed according to the Common Terminology Criteria for AEs (CTCAE version 4).

Frequency of adverse events (AE) and serious adverse events (SAE) verified during the study. Safety analyses will be reported by actual treatment group and on the Non-focal Progression Set. AE and SAE will be assessed according to the Common Terminology Criteria for AEs (CTCAE version 4).

Severity of adverse events (AE) and serious adverse events (SAE) verified during the study. Safety analyses will be reported by actual treatment group and on the Non-focal Progression Set. AE and SAE will be assessed according to the Common Terminology Criteria for AEs (CTCAE version 4).

Timing of adverse events (AE) and serious adverse events (SAE) verified during the study. Safety analyses will be reported by actual treatment group and on the Non-focal Progression Set. AE and SAE will be assessed according to the Common Terminology Criteria for AEs (CTCAE version 4).

Changes in blood pressure during and following vemurafenib + cobimetinib administration. Blood pressure will be measured in mmHg (millimetres of mercury).

Changes in heart rate during and following vemurafenib + cobimetinib administration. Heart rate will be measured in bpm (beats per minute).

Changes in temperature during and following vemurafenib + cobimetinib administration. Temperature will be measured in °C (degrees centigrade).

Changes in respiratory rate during and following vemurafenib + cobimetinib administration. Respiratory rate will be measured in breaths per minute.

Changes in clinical laboratory results during and following vemurafenib + cobimetinib administration. Laboratory results will be assessed according to the Common Terminology Criteria for AEs (CTCAE version 4).

Intergruppo Melanoma Italiano

Death

Immunomodulating Agents

BCD-217 followed by prolgolimab 1 mg/kg monotherapy.

Subject recieves BCD-217 0.2 mL/kg, which is equivalent to 1 mg/kg nurulimab + 3 mg/kg prolgolimab, as an intravenous infusion once every 3 weeks (Q3W) simultaneously with placebo, a total of 4 intravenous infusions. Beginning with the 5th infusion, subjects are switched to prolgolimab 1 mg/kg monotherapy once every 2 weeks (Q2W).

BCD-217

Subject recieves prolgolimab 3 mg/kg as an intravenous infusion once every 3 weeks (Q3W) simultaneously with placebo, a total of 4 intravenous infusions. Beginning with the 5th infusion, subjects are switched to prolgolimab 1 mg/kg monotherapy once every 2 weeks (Q2W).

BCD-100

Placebo

Anna A Siliutina, MD PhD

Fedor B Kriukov, MD PhD

Igor A Sharf

Vitalii S Volkov

Vasilii N Belyakovskii

Dmitrii P Norik

Nikolaii B Ermakov

Svetlana A Demidova

Natalia I Ivanova

Aleksei L Obukhov

Amit Bhargava, MD

M S Athiyamaan, MD

Prabhat G Bhargava, MD

Ajay O Mehta, MD

Rajnish Nagarkar, MD

Bhushan Nemade, MD

Sameer Rastogi, MD

Chetanavata Deshmukh, MD

Rakesh Neve, MD

Vaibhav Amale, MD

Kaushal Patel, MD

Anshul Agrawal, MD

Natalya V Fadeeva, MD, PhD

Victoria V Chistyakova

Yana S Chapko, MD

Sergei A Kolomiets

Oleg A Gladkov

Olga V Kurchenkova

Mariia V Smagina

Sufia Z Safina, MD

Artur Z Azanov

Vera A Vaschenko

Igor O Belogortsev

Leo Demidov

Igor A Utiashev

Elena V Poddubskaya

Elena F Satirova

Anastasiia S Mochalova

Daniil L Stroyakovsky, MD, PhD

Marina A Lyadova

Mikhail Yu Fedyanin

Irina S Shumskaya

Artem A Zeidlits

Vadim V Kozlov

Natalia A Falaleeva

Anastasiya V Zimina

Svetlana A Protsenko

Svetlana V Odintsova, MD

Julia V Semiletova

Ivan V Rikov

Sergei V Orlov

Timur T Agishev

Andrei V Kutkovich

Ivan S Sardaryan

Timur T Andabekov, PhD in Medicine

Artem N Poltoratski

Konstantin D Pen'kov

Mikhail V Kopp

Vladimir Moiseenko, MD

Pavel Skopin, PhD

DmitriI V Kirtbaya

Dmitrii V Gladishev

Nadezhda V Kovalenko, MD

Nikolay V Kislov

The aim of study is to investigate the efficacy, safety, immunogenicity, pharmacokinetics, and pharmacodynamics of BCD-217 followed by prolgolimab monotherapy versus prolgolimab monotherapy as first-line therapy in subjects with unresectable or metastatic melanoma.

This study is designed as a phase III, randomized, double-blind, placebo-controlled study.

After the stratification procedure, subjects are randomized in a 1:1 ratio into 2 groups:

* BCD-217 + placebo (4 doses) → prolgolimab (BCD-217 group)
* Prolgolimab + placebo (4 doses) → prolgolimab (BCD-100 monotherapy group)

A Clinical Study of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma

A Double-Blind Placebo-Controlled Comparative Randomized Clinical Study of the Efficacy and Safety of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma

Biocad

Neoplasm Metastasis

Abdominal Neoplasms

Neoplastic Processes

Patients with stage IV malignant melanoma with abdominal metastasis (M1c) that underwent abdominal surgery with metastasectomy during the study period.

Emergency or elective surgery on indications related to abdominally metastasized malignant melanoma

Abdominal surgery with metastasectomy

The aim is to conduct a single centre retrospective study of all patients with stage IV melanoma that underwent surgery for metastases at Sahlgrenska University Hospital between 2010-01-01 and 2018-12-31. Pre- and postoperative data will be collected from digital medical records, the Swedish Cancer Registry, the Swedish Cause of Death Register as well as from the national Swedish cancer patient database (INCA). If needed, patient records will be collected from other hospitals. Results will be presented in written format as a summary and analysis of the characteristics of the cases operated on during the inclusion period.

The aim is to identify predictive and prognostic factors for outcome and complications in the surgical treatment of stage IV metastatic melanoma.

Surgery for Gastrointestinal Metastases of Malignant Melanoma - a Single Center Retrospective Cohort Study

Complications according to Clavien-Dindo within 90 days.

Vastra Gotaland Region

Associate Professor, Senior Consultant Surgeon

Dacarbazine

Carmustine

Antineoplastic Agents, Alkylating

Alkylating Agents

Dacarbazine IV - Day 1; Carmustine IV - Day 2; Neulasta SC - Day 3

Neulasta

Jordan Waypa, FNP

The purpose of this study is to determine whether dacarbazine and carmustine at the doses and schedule used in this study will help to increase tumor shrinkage.

In this phase II trial, patients with stage IV melanoma will be treated with dacarbazine and carmustine commonly used in this cancer, but given using a schedule that might theoretically improve on this combination. Patients on this study will be assessed in terms of toxicity, response rate, median duration of response, median time to disease progression, and median survival.

Dacarbazine and Carmustine in Metastatic Melanoma

Phase II Trial of Sequenced Chemotherapy With Dacarbazine and Carmustine With Neulasta® Support in Previously Treated Metastatic Melanoma

Progression free survival of patients with Stage IV melanoma who have had disease progression on at least one prior systemic therapy

To determine the response rate after being treated with Dacarbazine Carmustine

To determine the median duration of response for patients who received Dacarbazine and Carmustine

Western Regional Medical Center

Number of Participants who received Dacarbazine Carmustine

Received Treatment

Age, Categorical

Sex: Female, Male

United States

Region of Enrollment

Jessica L. Coats

Number of participants who received Dacarbazine + Carmustine Progression Free survival at 8 weeks

Participants 8 Week Survival.

Data not collected. The study has been terminated due to the PI no longer being employed at CTCA and not having rights to the trial information."After much effort, results were not able to be retained.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
To Evaluate the Efficacy Beyond Progression of Vemurafenib+Cobimetinib Associated With Local Treatment Compared to Second-line Treatment in Patients With BRAFV600+ Metastatic Melanoma in Focal Progression With First-line+Vemurafenib+Cobimetinib.	NCT03514901	Melanoma Metast... BRAF V600 Mutat...	Experimental co... Pembrolizumab o...	18 Years -	Intergruppo Melanoma Italiano
A Clinical Study of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma	NCT05732805	Melanoma Melanoma (Skin) Melanoma Stage ... Melanoma Stage ... Melanoma Unrese... Melanoma Metast... Melanoma Advanc...	BCD-217 BCD-100 Placebo	18 Years -	Biocad
To Evaluate the Efficacy Beyond Progression of Vemurafenib+Cobimetinib Associated With Local Treatment Compared to Second-line Treatment in Patients With BRAFV600+ Metastatic Melanoma in Focal Progression With First-line+Vemurafenib+Cobimetinib.	NCT03514901	Melanoma Metast... BRAF V600 Mutat...	Experimental co... Pembrolizumab o...	18 Years -	Intergruppo Melanoma Italiano
Surgery for Gastrointestinal Metastases of Malignant Melanoma - a Single Center Retrospective Cohort Study	NCT03879395	Melanoma Stage ... Melanoma Metast... Abdominal Tumor	Abdominal surge...	18 Years -	Vastra Gotaland Region
Surgery for Gastrointestinal Metastases of Malignant Melanoma - a Single Center Retrospective Cohort Study	NCT03879395	Melanoma Stage ... Melanoma Metast... Abdominal Tumor	Abdominal surge...	18 Years -	Vastra Gotaland Region
To Evaluate the Efficacy Beyond Progression of Vemurafenib+Cobimetinib Associated With Local Treatment Compared to Second-line Treatment in Patients With BRAFV600+ Metastatic Melanoma in Focal Progression With First-line+Vemurafenib+Cobimetinib.	NCT03514901	Melanoma Metast... BRAF V600 Mutat...	Experimental co... Pembrolizumab o...	18 Years -	Intergruppo Melanoma Italiano
A Clinical Study of BCD-217 (Nurulimab + Prolgolimab) Followed by Anti-PD-1 Compared to Anti-PD-1 Monotherapy as First-Line Treatment in Subjects With Unresectable/Metastatic Melanoma	NCT05732805	Melanoma Melanoma (Skin) Melanoma Stage ... Melanoma Stage ... Melanoma Unrese... Melanoma Metast... Melanoma Advanc...	BCD-217 BCD-100 Placebo	18 Years -	Biocad
Dacarbazine and Carmustine in Metastatic Melanoma	NCT01692691	Melanoma Metast...	Dacarbazine Carmustine Neulasta	18 Years -	Western Regional Medical Center

Spots Global Cancer Trial Database for melanoma metastatic