Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

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

Neuroendocrine Tumor

Neuroepithelioma

Antineoplastic Agents

All Drugs and Chemicals

Atezolizumab

Vemurafenib

Immune Checkpoint Inhibitors

Antineoplastic Agents, Immunological

Protein Kinase Inhibitors

Enzyme Inhibitors

Arm A BRAF mutated patients. Over a period of 6 weeks (1) + (2):

1. Vemurafenib 960 mg bid p.o. from week 1 to week 6.
2. Cobimetinib 60 mg qd p.o. from week 1 to week 3 and week 5 to week 6. Week 4 off.

After surgery and a second screening period (up to six weeks): Atezolizumab 1200 mg IV for 52 weeks

Arm B BRAF mutated patients. Over a period of 6 weeks (1) + (2) + (3):

1. Vemurafenib 720 mg bid p.o. from week 1 to week 6.
2. Cobimetinib 60 mg qd p.o. from week 1 to week 3 and from week 5 to week 6. Week 4 off.
3. Atezolizumab 840 mg IV for 2 cycles (day 1 of week 4 and day 1 of week 7).

After surgery and a second screening period (up to six weeks): Atezolizumab 1200 mg IV for 52 weeks

Arm C BRAF WT patients. Over a period of six weeks (1) + (2):

1. Cobimetinib 60 mg qd p.o. from week 1 to week 3 and from week 5 to week 6,
2. Atezolizumab 840 mg IV for 2 cycles (day 1 of week 1 and day 1 of week 4).

After surgery and a second screening period (up to six weeks): Atezolizumab 1200 mg IV for 52 weeks

Cobimetinib 60 mg qd p.o. from week 1 to week 3 and week 5 to week 6. Week 4 off.

Cobimetinib 20 MG Oral Tablet

960 (arm A) /720 (arm B) mg bid p.o. from week 1 to week 6.

Vemurafenib 240 Mg Oral Capsule

840 mg IV for 2 cycles for Arm B and C. After surgery in all arms 1200 mg IV for 52 weeks

Atezolizumab 1200 MG in 20 ML Injection

Paolo Ascierto

Neoadjuvant plus adjuvant treatment with target therapy and immunotherapy given in combination or sequence may have an anti-tumour activity and may reduce the risk of relapse in patients with high-risk resectable melanoma (stage III B / C / D and oligometastatic stage IV).

Melanoma represents a considerable health burden and an ongoing area of unmet need in oncology. Despite melanoma accounts for only 1% of diagnosed skin cancers, it is the cause of most skin cancer-related deaths. Until recently, limited effective treatment options were available to patients with advanced melanoma. Historically, response rates to conventional chemotherapy and immunomodulation therapy (interleukin-2 or interferon-γ) have been reported at approximately 5-19%.

Adjuvant immune checkpoint blockade (ICB) and target therapy improve outcomes of patients with high-risk resectable melanoma. It has recently been demonstrated that treatment with neoadjuvant and adjuvant targeted therapy (dabrafenib and trametinib) is associated with a high pathologic complete response (pCR) rate and improved outcomes over surgery alone. However, treatment with ICB has not been well studied in the neoadjuvant setting, despite preclinical studies suggesting that neoadjuvant administration of ICB is associated with improved survival and enhanced anti-tumour immune responses compared to the same therapy administered in the adjuvant setting.

The advantage of neoadjuvant trials is the availability of blood and tumour tissue samples before and after systemic therapy for the conduct of novel mechanistic and biomarker studies in the circulation and the tumour microenvironment.

Prospective neoadjuvant clinical trials with targeted (dabrafenib/trametinib combo) or immunotherapeutic agents (nivolumab alone or nivolumab/ipilimumab combo) and combinations are now running in a subgroup of highrisk melanoma patients with pooled overall promising preliminary results of high rates of pathologic complete responses (pCRs, 30-50%) and early data of positive correlation between pCR and relapse-free survival. Based on the available results to date, we aim to conduct a randomized, noncomparative phase II trial to define the role of neoadjuvant plus adjuvant target and immunotherapy, given in combination or sequence, in patients with high risk surgically resectable melanoma.This approach has the potential to define whether neoadjuvant treatment has antitumour activity and whether it reduces the risk of relapse after surgery.

The study will be conducted according to an open-label, randomized, not comparative phase II design. Three arms for a total of 88 patients will be considered.

BRAF mutated patients will be randomized in two arms: Arm A and Arm B (27 patients per arm). BRAF WT patients will be included in Arm C (34 patients).

Combination or Sequence of Vemurafenib, Cobimetinib, and Atezolizumab in High-risk, Resectable Melanoma

"NEOadjuvant Plus Adjuvant Therapy With Combination or Sequence of Vemurafenib, cobImetinib, and atezolizuMab in Patients With High-risk, Surgically Resectable BRAF Mutated and Wild-type Melanoma"

Defined as the lack of all signs of cancer in tissue samples removed during surgery

Defined as the time from randomisation to recurrence event or last follow-up

Defined as the time from the date of randomisation to the date of death due to any cause

Defined as the sum of pathologic complete responses (pCRs), near pathologic complete responses near pCRs) and pathologic partial responses (pPRs).

All AEs, Grade 3 to 4 AEs, serious adverse events (SAEs), deaths, AEs of special interest (AESIs), and AEs leading to treatment discontinuation or withdrawal from the study

Immunoscore, Circulating cytokines and chemokines profiling, Metabolomic profiling,Tumour mutational burden, Myeloid-derived suppressors cells, immune cell subtypes expression and lymphocyte activation, Additional analysis of protein levels (i.e. CCR5), DNA mutations, and/or mRNA analysis

Clinical Research Technology S.r.l.

Fondazione Melanoma Onlus

Respiratory Tract (Lung and Bronchial) Diseases

Carcinoma, Non-Small-Cell Lung

Lung Neoplasms

Carcinoma

Respiratory Tract Neoplasms

Thoracic Neoplasms

Lung Diseases

Respiratory Tract Diseases

Carcinoma, Bronchogenic

Bronchial Neoplasms

Amino Acids

Mitogens

Tyrosine Kinase Inhibitors

Erlotinib Hydrochloride

Tyrosine

Erlotinib (trade name: Tarceva®) (150mg oral daily) or Icotinib (trade name: Conmana®) (125mg oral three times a day) with concurrent radiotherapy to a total radiation dose of 60-66 Gray (Gy).

Erlotinib (trade name: Tarceva®) (150mg oral daily) or Icotinib (trade name: Conmana®) (125mg oral three times a day).

Erlotinib (trade name: Tarceva®) or Icotinib (trade name: Conmana®)

Concurrent radiotherapy total dose 60-66 Gy in 2 Gy fractions. One fraction per day, and 5 fractions per week.

Radiotherapy

Zhishuang Zheng, Dr

Zhishuang Zheng

Shixiu Wu, MD

Concurrent chemoradiotheray is the standard care for patients with locally advanced non-small cell lung cancer (NSCLC), but often accompanying with high toxicity and poor tolerability. Radiosensitization of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has been proved in preclinical studies, and the safety of TKI combined with thoracic radiotherapy has also been evaluated in several phase II trials. The aim of study is to investigate the efficacy and safety of thoracic radiotherapy combined with TKI in wild-type EGFR patients who refused or unsuitable for concurrent chemoradiotherapy.

RT Plus EGFR-TKI for Wild-type NSCLC

Thoracic Radiotherapy Combined With EGFR-TKI for Wild-type Non-small Cell Lung Cancer

Toxicity of the treatment will be evaluated according to the common toxicity criteria for adverse events version 3.0 (CTCAE v3.0).

Progression-free survival (PFS) will be calculated from the date of treatment initiation to the date of documented failure (local recurrence or metastasis occurrence) or the date of the last follow-up for those remaining.

Overall survival (OS) wiil be determined as the time (in months) between the first day of therapy and the last follow-up or the date of death.

Hangzhou Cancer Hospital

Breast Neoplasms

Breast Diseases

Fulvestrant

Estrogens

Estrogen Antagonists

Estrogen Receptor Antagonists

Antineoplastic Agents, Hormonal

Hormones

Hormone Antagonists

In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene

In post-menopausal patients with estrogen receptor positive locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene, and in patients whose tumors are have wild-type PIK3CA gene

BYL719 is an oral α-specific phosphatidylinositol-3-kinase (PI3K) inhibitor.

BYL719

In adult patients with advanced solid malignancies whose tumors have an alteration (mutation or amplification) of the PIK3CA gene.

Fulvestrant is an estrogen receptor antagonist, administered by monthly intramuscular injection

Novartis Pharmaceuticals

This is a first-in-man trial, in which BYL719 will be administered to adult patients with advanced solid tumors, whose tumors have an alteration of the PIK3CA gene and whose disease has progressed despite standard therapy or for whom no standard therapy exists. A combination of BYL719 with fulvestrant will also be investigated in post-menopausal patients with locally advanced or metastatic breast cancer whose tumors have an alteration of the PIK3CA gene. The single agent MTD dose expansion cohort and the fulvestrant combination MTD dose expansion cohort will also include ER+/HER2- breast cancer patients whose tumors have the wild type PIK3CA gene

A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

A Phase IA, Multicenter, Open-label Dose Escalation Study of Oral BYL719, in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene

MTD (or RP2D) of oral BYL719 as single agent and in combination with fulvestrant.

Safety and tolerability: type, intensity, severity and seriousness of adverse events (AE) according to NCI CTCAE v. 4.0.

Objective tumor response rate (ORR), defined as the sum of complete response and partial response as best reported response by RECIST 1.0 criteria (Novartis v2.0 guideline)

Symptoms and General Pathology

Immune System Diseases

Pruritus

Mastocytosis

Flushing

Mastocytosis, Systemic

Neoplasms, Connective Tissue

Neoplasms, Connective and Soft Tissue

Mast Cell Activation Disorders

Systemic Mastocytosis

Psychotropic Drugs

Respiratory System Agents

Anti-Allergic Agents

Anti-Inflammatory Agents

Histamine Antagonists

Histamine H1 Antagonists

Antidepressive Agents

Leukotriene Antagonists

Proton Pump Inhibitors

Cromolyn Sodium

Experimental Arm:

Masitinib (titration to 6.0 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC).

Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Placebo Comparator:

Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Masitinib

Placebo

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglycate, antidepressants, leukotriene antagonists and corticosteroids.

Best Supportive Care

Clinical Study Coordinator

Cristina Bulai Livideanu, MD, MSc

The purpose of this study is to evaluate the efficacy and safety of oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release, unresponsive to optimal symptomatic treatment.

Masitinib is a selective tyrosine kinase inhibitor that modulates mast cell activity via inhibition of c-Kit, Lyn and Fyn kinase signaling pathways. This is a multicenter, randomized, double-blind, placebo-controlled, 2-parallel-group, trial comparing oral masitinib versus placebo in the treatment of patients suffering from smouldering or indolent systemic mastocytosis with severe symptoms of mast cell mediator release (also referred to as handicaps), unresponsive to optimal symptomatic treatment. The treatment period is 24 weeks. Participants receive masitinib (3.0 mg/kg/day), given orally twice daily, with a dose escalation to 4.5 mg/kg/day after 4 weeks of treatment, followed by dose escalation to 6.0 mg/kg/day after 4 weeks of treatment. Each ascending dose titration is subjected to a safety control.

Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment

Phase 3 Study to Compare Oral Masitinib to Placebo in Treatment of Patients With Smouldering or Indolent Severe Systemic Mastocytosis, Unresponsive to Optimal Symptomatic Treatment

Cumulative response in at least one of three severe baseline symptoms of mast cell mediator release (pruritus, flushes, or depression). Response was defined as a 75% improvement from baseline for any of these three symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 15 possible responses depending on the number of severe baseline symptoms).

Cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response is defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).

Cumulative response in at least one of two severe baseline symptoms of mast cell mediator release (pruritus or flushes). Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 10 possible responses depending on the number of severe baseline symptoms).

Cumulative response on each of the individual handicaps. Response is defined as a 75% improvement from baseline for either of these two symptoms. Cumulative response is defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period.

AB Science

Mastocytosis, Cutaneous

Mastocytoma

Cutaneous Mastocytosis

Anti-Infective Agents

Interferons

Interferon-alpha

Cladribine

2-chloro-3'-deoxyadenosine

Masitinib (6 mg/kg/day) administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Matching placebo administered as an add-on to optimal concomitant symptomatic treatment (i.e. best supportive care, BSC)

Optimal concomitant symptomatic treatments. Includes: H1- and H2-antihistamines, proton pump inhibitors (PPI), sodium cromoglicate, antidepressants, leukotriene antagonists, interferon-alpha, 2-CdA, and corticosteroids.

Olivier Lortholary, MD, PhD

The objective of this study is to compare the safety and efficacy of masitinib (AB1010) to placebo in patients with mastocytosis with handicap.

This was a prospective, multicenter, randomized, placebo-controlled, parallel-group, phase 3 study, conducted in 15 countries, evaluating the efficacy and safety of masitinib (6 mg/kg/day administered orally in two daily intakes over 24-weeks with a double-blind extension period possible) for the treatment of indolent systemic mastocytosis, smoldering mastocytosis or cutaneous mastocytosis, in patients with mast cells mediator release symptoms that are refractory to conventional symptomatic treatment.

A study protocol amendment restricted enrolment to patients with severe indolent and smoldering systemic mastocytosis. The objective of this phase 3 study was therefore to evaluate masitinib efficacy and safety in severe systemic mastocytosis patients, with or without D816V mutation of c-Kit. The primary objective of the phase 3 study was to detect a statistically significant difference between masitinib (plus optimal concomitant symptomatic treatments) and placebo (plus optimal concomitant symptomatic treatments) in cumulative response on four severe symptoms, referred to also as handicaps.

Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis

Randomized, Placebo-controlled, Phase 3 Study to Compare Efficacy and Safety of Masitinib at 6 mg/kg/Day to Placebo in Treatment of Patients With Smouldering Systemic, Indolent Systemic or Cutaneous Mastocytosis With Handicap

The prospectively declared primary endpoint (4R75%) was cumulative response in at least one of four severe baseline symptoms of mast cell mediator release (pruritus, flushes, depression, or asthenia). Response was defined as a 75% improvement from baseline for any of these four symptoms. Cumulative response was defined as the number of actual responses between weeks 8 and 24, divided by the total number of possible responses over the same treatment period (ie, with five scheduled visits, each patient had a maximum of five to 20 possible responses depending on the number of severe baseline symptoms).

Cumulative response in at least one of three severe baseline symptoms (pruritus, flushes, or depression)

Cumulative response in at least one of three severe baseline symptoms (pruritus or flushes)

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Combination or Sequence of Vemurafenib, Cobimetinib, and Atezolizumab in High-risk, Resectable Melanoma	NCT04722575	Melanoma	Cobimetinib 20 ... Vemurafenib 240... Atezolizumab 12...	18 Years -	Fondazione Melanoma Onlus
RT Plus EGFR-TKI for Wild-type NSCLC	NCT02738983	Non-small Cell ... Epidermal Growt...	Erlotinib (trad... Radiotherapy	19 Years -	Hangzhou Cancer Hospital
RT Plus EGFR-TKI for Wild-type NSCLC	NCT02738983	Non-small Cell ... Epidermal Growt...	Erlotinib (trad... Radiotherapy	19 Years -	Hangzhou Cancer Hospital
Combination or Sequence of Vemurafenib, Cobimetinib, and Atezolizumab in High-risk, Resectable Melanoma	NCT04722575	Melanoma	Cobimetinib 20 ... Vemurafenib 240... Atezolizumab 12...	18 Years -	Fondazione Melanoma Onlus
A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene	NCT01219699	Advanced Solid ... Estrogen Recept...	BYL719 Fulvestrant	18 Years -	Novartis
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis Unresponsive to Optimal Symptomatic Treatment	NCT04333108	Indolent System...	Masitinib Placebo Best Supportive...	18 Years - 75 Years	AB Science
A Study of BYL719 in Adult Patients With Advanced Solid Malignancies, Whose Tumors Have an Alteration of the PIK3CA Gene	NCT01219699	Advanced Solid ... Estrogen Recept...	BYL719 Fulvestrant	18 Years -	Novartis
Masitinib in Severe Indolent or Smoldering Systemic Mastocytosis	NCT00814073	Indolent System...	Masitinib Placebo Best Supportive...	18 Years - 75 Years	AB Science

Spots Global Cancer Trial Database for wild type

Every month we try and update this database with for wild type cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Spots Global Cancer Trial Database for wild type

Every month we try and update this database with for wild type cancer trials from around the world to help patients and their families find trials that might be right for them. We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.

Every month we try and update this database with for wild type cancer trials from around the world to help patients and their families find trials that might be right for them.
We offer this 100% free of charge and do not endorse any of the trials listed here, we hope it helps you or a loved one.