Neoplasms

Skin and Connective Tissue Diseases

All Conditions

Rare Diseases

Melanoma

Melanoma, Cutaneous Malignant

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

Paclitaxel

Albumin-Bound Paclitaxel

Nintedanib

Tubulin Modulators

Antimitotic Agents

Protein Kinase Inhibitors

Enzyme Inhibitors

Nintedanib (150 or 200mg BID) for up to 48 weeks combined with paclitaxel 90mg/m2 BSA day 1, 8, 15 q28 days for a maximum of 6 courses

Placebo (150 or 200mg BID) for up to 48 weeks combined with paclitaxel 90mg/m2 BSA day 1, 8, 15 q28 days for a maximum of 6 courses

Nintedanib-Placebo

Paclitaxel as 90mg/mw infusion day 1, 8, 15 q28 (6 cycles)

Dirk Schadendorf, Prof. Dr.

This is a multicenter, randomized, double-blind, placebo-controlled phase I/II trial designed to characterize the safety and estimate the efficacy of nintedanib when combined with paclitaxel chemotherapy compared with paclitaxel chemotherapy alone in patients with BRAF wild type metastatic melanoma not previously treated with taxanes or kinase inhibitors.

Study Phase I: Run-In-Phase Based on acceptable safety data for nintedanib monotherapy, a rapid dose finding will be conducted in a classical 3+3 design. Predefined dose levels are 150 mg (dose level 1) and 200 mg (dose level 2) nintedanib, twice daily, with weekly paclitaxel 90 mg/m2.

Study Phase II Patients with advanced (unresectable Stage III or IV) BRaf V600 wild type melanoma (n=120) will be randomized (1:1) to receive either Nintedanib (150 or 200 mg BID depending on results of phase I) in combination with paclitaxel or Placebo in combination with paclitaxel.

Total study duration per patient: approximately 12 months of therapy + Follow up until end of study

All patients enrolled in either phase I or phase II will be treated according to the following treatment plan:

Week 1 - 24:

Chemotherapy with paclitaxel combined with nintedanib/placebo

Week 25 - 48:

Extended monotherapy with nintedanib/placebo

Week 52 (or approximately 4 weeks after last treatment dose):

End of Treatment visit

Follow up:

After end of treatment the survival, disease status and further therapies of each patient will be assessed every 3 months until death, progression of disease or end of study whichever occurs first

Efficacy and Safety of Nintedanib Combined With Paclitaxel Chemotherapy for Patients With BRAF wt Metastatic Melanoma

Phase I/II,Multicenter,Randomized,Double-blind,Placebo-controlled Trial Evaluating the Efficacy and Safety of Nintedanib/Vargatef in Combination With Paclitaxel Chemotherapy for Treatment of Patients With BRAF Wildtype Metastatic Melanoma

Time from administration of first study drug to the date of first documented progression or death due to any cause, whichever occurs first

Time from the date of first administration of study drug to the date of death due to any cause.

Reporting of adverse events from the date of first administration of study drug until 30 days after last administration of study drug

Quality of life during therapy (i.e. until end of treatment visit)

Boehringer Ingelheim

medac GmbH

Alcedis GmbH

Prof. Dr. med. Dirk Schadendorf

Symptoms and General Pathology

Neoplasm Metastasis

Neoplastic Processes

Anti-Infective Agents

Bleomycin

Anti-Bacterial Agents

Antibiotics, Antitubercular

ECT will be performed directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 100 μs, 5 kHz). Triggering of the electrical pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart. The type of electrode used will be selected according to the size and location of the tumors.

ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 100 μs, 5 kHz). Triggering of the electrical pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart. The type of electrode used will be selected according to the size and location of the tumors.

Electrochemotherapy with Intratumoral Cysplatin

Electrochemotherapy with Intravenous Bleomycin

Barbara Perić

In the last 10 years, the treatment of metastatic cutaneous melanoma has changed dramatically. The new systemic treatment with immunotherapy has led to a dramatic improvement in quality of life and overall survival. Systemic treatment means that the patient receives the drug as an infusion into a vein. Unfortunately, we know that immunotherapy is not equally successful in all patients. Recent studies have shown that the success of the treatment is not only influenced by the cellular composition of the metastasis, but also by its surroundings. This is called tumor microenvironment. Depending on the differences in the composition of this microenvironment, some metastases can be described as immunologically hot and others as immunologically cold. Immunologically hot metastases respond better to immunotherapy than immunologically cold metastases.

Studies have shown that with some interventions we can change the tumor microenvironment from being immune-cold to being immune-hot. Electrochemotherapy is one of the interventions that might improve the efficacy of immunotherapy in cutaneous melanoma. Electrochemotherapy is an established method for the local treatment of tumors, in which only a certain tumor is treated with special electrodes, to which a weak electric current is applied. We hypothesize that electrochemotherapy stimulates the body's own immune response and enables more effective treatment. Since immunotherapy also stimulates the body's own immune response to cutaneous melanoma cells, the interaction of the two drugs could be even more successful. Recent research results support this assumption.

The primary objective is to evaluate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy, based on the histologic analysis of treated and untreated metastases before and after treatment. The secondary aim is to determine whether the changes in the tumor microenvironment differ depending on the chemotherapeutic agent used.

The results will help us to better understand the synergistic effects of electrochemotherapy and immunotherapy on cutaneous melanoma metastases. The combination of systemic immunotherapy and electrochemotherapy could become an important treatment method for patients with metastatic melanoma.

The study is prospective. The primary objective is to evaluate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy (ECT), based on the histologic analysis of treated and untreated metastases before and after treatment. The secondary aim is to determine whether the changes in the tumor microenvironment differ depending on the chemotherapeutic agent used.

In the study 10-15 patients will be enrolled and devided in two arms, ECT with bleomycin and ECT with cysplatin.

ECT will be offered to patients with cuteaneous melanoma and at least 5 in-transit or distant cutaneous and/or subcutaneous melanoma metastases regardless of previous treatments. The decision will be made in a multidisciplinary tumor board. The choice of chemotherapeuthic drug will depend on the size andnumber of lesions to be treated. Inclusion in the study has no influence on the decision regarding the timing of treatment with immunotherapy. Treatment with immunotherapy will later be included as a factor in the statistical analysis.

ECT will be performed according to the standard operating procedures for the treatment of cutaneous and subcutaneous tumors with ECT. ECT will be performed within 8 - 28 minutes after intravenous bolus administration of bleomycin (15.000 IU/m2 BSA) or directly after the intratumorally administration of cysplatin (0,5-2 mg/cm3 tumor). CliniporatorTM (IGEA S.P.A., Carpi, Italy) will be used to apply the pulses (8 pulses, 1300 V/cm, 100 μs, 5 kHz). Triggering of the electrical pulses will be synchronized with ECG signals, through the ECG triggering device AccuSync to avoid delivery of pulses in vulnerable period of the heart. The type of electrode used will be selected according to the size and location of the tumors.

One cutaneous/subcutaneous metastasis will be excised before ECT. One treated cutaneous/subcutaneous metastasis will be excised 2-4 and 9-13 days after the procedure. An untreated cutaneous/subcutaneous metastasis will be excised on day 9-13. The excisions will be performed under local anesthesia. All patients will be enrolled in the study after the procedures and the study have been explained to them in detail and they have signed an informed consent form. A venous blood sample will be taken at the same time points (before ECT, 2-4 days and 9-13 days after ECT).

Histological examination, assessment of the degree of regression and the presence of tumor infiltrating lymphocytes (TIL) will be performed according to standardized procedures on 2-3 μm thick tissue sections, previously fixed in formalin and embedded in paraffin (FFPE), stained with the hematoxylin-eosin (HE) staining method.

Immunohistochemical characterization of the tumor microenvironment will be performed on 2-4 μm thick tissue sections pre-fixed in formalin and embedded in paraffin. We will use commercially available primary monoclonal antibodies to define the tumor inflammatory infiltrate, stroma and vasculature. We will use the following antibodies: CD3, CD4, CD8, CD56, CD163, FoxP3, ERG, PGM1, CD274 (PD-L1). The choice of antibodies used and the method of pathohistologic analysis may change depending on the results. Specific binding of primary antibodies will be visualized using the recommended three-step detection system OptiView DAB IHC Detection Kit (Cat. No. 760-700; manufactured by Ventana ROCHE inc., Tucson, AZ, USA) according to the manufacturer's instructions. The analysis will be performed by two independent pathologists.

We will also collect the information about previous treatments for cutaneous melanoma and photographic documentation of the effectiveness of ECT treatment. Patients will also fill out internationally recognized, validated quality of life questionnaires (EORTC QLQ-C 30 and EQ-5D-5L) at entollment, after ECT, 3 months, 6 months and 12 months after ECT and then once a year during the follow-up period.

Electrochemotherapy with intratumoural cysplatin is recommended for smaller (less than 3 cm) and fewer tumours (up to 10 lesions), while electrochemotherapy with intravenous bleomycin is preferable for multiple and larger tumours.

Electrochemotherapy Induces Changes in the Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma

The primary objective is to investigate the changes in the tumor microenvironment of cutaneous and subcutaneous melanoma metastases induced by electrochemotherapy, based on the histological evaluation of treated and untreated metastases before and after treatment.

The secondary aim is to determine whether the changes in the tumor microenviroment differ depending on the chemotherapeutic agent used - bleomycin intravenously or cysplatin intratumorally

Slovenian Research and Innovation Agency

Institute of Oncology Ljubljana

Bone Density Conservation Agents

Micronutrients

Vitamins

Herbal and Botanical

Vitamin D

Cholecalciferol

Trace Elements

Hormones

Calcium

Calcium, Dietary

Vitamin D3

Calciferol

Olive

Every month 100 000 units of Vitamin D in syringe oral dispenser is taken . Study duration is maximum 3,5 years or until relapse occurs

Every month 100 000 units of vitamin D in syringe Oral dispenser is taken. Study duration is maximum of 3.5 years or until relapse occurs

* prospective interventional randomized double blind placebo controlled trail
* clinical setting (tertiary university hospital)
* investigator driven, no pharmaceutical sponsor
* cutaneous malignant melanoma patients
* add- on study (placebo or vitamin D) on top of optimal standard care
* 1:1 inclusion ratio (placebo:Vitamin D)
* randomisation after informed consent and screening

arachides oleum raffinatum

Marjan Garmyn, MD, PhD

To assess whether vitamin D supplementation after surgery of a first cutaneous malignant melanoma protects against relapse of the disease.

To assess whether vitamin D supplementation, in the follow up period after diagnosis and surgery of a first cutaneous malignant melanoma, has a protective effect on relapse of cutaneous malignant melanoma and whether this protective effect correlates with vitamin D levels in serum and vitamin D receptor (VDR) immunoreactivity in the primary tumor.

Vitamin D Supplementation in Cutaneous Malignant Melanoma Outcome

Incidence and severity of adverse events will be recorded every 3 months up to final study visit.

Disease free survival will be the primary endpoint of this phase III trial. Patients are enrolled during a recruitment phase of three years maximum. Study duration for one patient is maximum 3,5 years or until relapse occurs.

Vitamin D levels at diagnosis will be correlated with melanoma subtype, as assessed clinically and histologically.

Vitamin D levels at diagnosis will be correlated with melanoma site, as clinically recorded.

25(OH)D3 serum levels will be recorded at diagnosis and at 6 months intervals up to final study visit. Genetic variability of Vitamin D pathway will be correlated with 25(OH)D3 serum levels

Vitamin D levels at diagnosis and genetic variability of the vitamin D pathway will be correlated with stage of melanoma patient at diagnosis according to the 2009 American Joint Committee of Cancer (AJCC) Melanoma staging and classification

KU Leuven

Universitaire Ziekenhuizen KU Leuven

Biopsy

Falk G Bechara, PD Dr.

Peter Altmeyer, Prof. Dr.

Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). This study will be an exploratory analysis by miRNA expression profiling using microarrays.

Perturbations in microRNA (miRNA) expression profiles has been reported for cutaneous malignant melanoma (CMM). With regards to a rapidly growing number of newly discovered miRNA sequences, the availability of up-to-date miRNA expression profiles for primary cutaneous malignant melanoma (PCMM), cutaneous malignant melanoma metastases (CMMM) and benign melanocytic naevi (BMN) is limited. Patients with PCMM, CMMM and BMN are included in the study to perform an exploratory analysis by miRNA expression profiling using microarrays. Expression levels of miRNA candidates will be validated by TaqMan real-time quantitative polymerase chain reaction (RT-PCR).

Comparative Microarray Analysis in Primary Cutaneous Malignant Melanoma

Comparative Microarray Analysis of microRNA Expression Profiles in Primary Cutaneous Malignant Melanoma, Cutaneous Malignant Melanoma Metastases and Benign Melanocytic Naevi

Ruhr University of Bochum

Principal Investigator

Urinary Tract, Sexual Organs, and Pregnancy Conditions

Carcinoma, Renal Cell

Carcinoma

Adenocarcinoma

Neoplasms, Glandular and Epithelial

Kidney Neoplasms

Urologic Neoplasms

Urogenital Neoplasms

Urogenital Diseases

Female Urogenital Diseases

Pregnancy Complications

Female Urogenital Diseases and Pregnancy Complications

Kidney Diseases

Urologic Diseases

Male Urogenital Diseases

Renal Cell Carcinoma

Immunomodulating Agents

Immunologic Factors

Participants will receive one treatment of brachytherapy on treatment day 1 (LDRD1). After a minimum of 7 days but no more than 30 days to allow antigenic release, participants will then begin immunotherapy treatment with SOC immunotherapy at the standard FDA-approved dose. Standard immunotherapy will be administered on D1 of every standard of care cycle (either 14, 21, 28, or 42 day cycle) at the standard dose. Participants can receive up to 1 year of SOC immunotherapy.

Low Dose Rate Brachytherapy (LDR)

Standard or care immunotherapy will be administered at the FDA approved dose via IV infusion.

Standard-of-Care Immunotherapy

Jay Ciezki, MD

Jay Ciezki

This is a pilot study of combination low dose rate brachytherapy (LDR) added to standard of care (SOC) immunotherapy in stage III and IV melanoma, stage IV renal call cancer, and stage IV urothelial cancer.

The purpose of this study is to evaluate the effect of combining LDR with immune checkpoint inhibition in stage III and IV melanoma, stage IV renal call cancer, and stage IV urothelial cancer. This involves the addition of a treatment called brachytherapy to SOC immunotherapy. Brachytherapy is a form of radiation therapy where radioactive pellets are placed within a tumor to temporarily irradiate the tumor at a low level. This is the first time that this combination (immunotherapy and brachytherapy) has been used in humans.

The objectives of this study are to evaluate the effect of combining LDR with immunotherapy, determine safety and feasibility, generate a toxicity profile, evaluate response, and overall survival.

Low-Dose-Rate Brachytherapy Combined With Immune Checkpoint Inhibition in Cancer

Individual participant data will not be shared but the study team is expecting to publish the data

iRECIST was developed by the RECIST working group for the use of RECIST version 1.1 in cancer immunotherapy trials, to ensure consistent design and data collection.

ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on the Response Evaluation Criteria in Solid Tumors (iRECIST or RECIST v1.1) at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

ORR is defined as the number of patients achieving a complete response (CR) or partial response (PR) based on iRECIST or RECIST v1.1 at any time during the study. CR = disappearance of all target lesions, PR is =\>30% decrease in sum of diameters of target lesions, progressive disease (PD) is \>20% increase in sum of diameters of target lesions, stable disease (SD) is \<30% decrease or \<20% increase in sum of diameters of target lesions. Estimation based on CT or MRI scans

Case Comprehensive Cancer Center

We will send 3 sets of materials via mail, containing information about melanoma prevention and detection, 1 set each month for 3 months. Materials published by:

* The American Cancer Society
* The American Academy of Dermatology
* The Skin Cancer Foundation

The pamphlets contain information about ways to reduce risk for skin cancer including:

* Sun protection practices
* Risk factors for melanoma
* Information about what melanoma looks like
* How to do skin self-examinations

There will also be a telephone discussion with a health educator, discussing melanoma and other information contained in the pamphlets.

Reading materials and discussions

We will send 3 separate pamphlets created specifically for participants. We will send 1 pamphlet each month for 3 months. The information in the pamphlets will be based on answers from the first survey. These pamphlets will contain information about:

* Melanoma and skin cancer protection guidelines
* The benefits of skin screening practices
* Ways to protect yourself from the sun

In addition to these pamphlets, there will be a telephone discussion with a health educator to discuss melanoma and other information contained in the pamphlets.

Both groups will complete 3 surveys; at the beginning, 3 months later, 6 months after the second survey. Each survey will ask about:

* knowledge of melanoma
* current and past skin cancer screening practices
* current and past sun protection practices
* attitudes about skin cancer and sun protection
* feelings about relative's melanoma diagnosis and treatment

Questionnaires

Paul Jacobsen, Ph.D.

Sharon L Manne, PhD

Michael Ming, MD

The purpose of the investigators' study is to find the best way to provide information about sun protection and skin cancer detection. The investigators want to see which of two methods most improves sun protection and screening attitudes and practices. The investigators hope to improve these attitudes and practices among people who are at higher risk for melanoma. People at higher risk for melanoma are first degree relatives (mother, father, sibling or child) of people diagnosed with melanoma.

Eligible patients will be contacted to find out whether they have any living first degree relatives that we may contact to discuss their participation in our study.

Eligible first degree relatives (FDRs) will participate in our study as outlined under Interventions.

Tailored Intervention for Melanoma Patient's Families

National Cancer Institute (NCI)

Fox Chase Cancer Center

Pharmaceutical Solutions

Nutritional supplement Oncoxin-Viusid 25 mL in oral solution twice a day

Oncoxin-Viusid supplement before/during/after standard surgical and adjuvant treatment or chemotherapy.

Oncoxin-Viusid

Olaine R. Gray Lovio, Dr.

Malignant melanoma, responsible for 75% of deaths from skin cancer. Current therapeutic options have poor response, many adverse events and high costs. For this reason, a study with nutritional supplement Oncoxin-Viusid was carried out. According to previous studies, it has an antitumor, immunomodulatory effect and to potentiate the antiproliferative effect of standard chemotherapeutic agents in different locations and stages of cancer.

Performed at Manuel Fajardo Surgical Clinical University Hospital in Havana, Cuba from September 2014 to April 2018, following a proof of concept open label study, with no control group in 20 patients diagnosed histologically in Fajardo Hospital or Oncology Institute, as Melanoma, primary cutaneous stage IIB-IIIA. All received conventional surgical treatment and oral Oncoxin-Viusid (25 ml 2 times a day for one year), where it was also indicated adjuvant treatment or chemotherapy. All were evaluated monthly the first year and semesterly the second year. Complying with the provisions of the Helsinki Act.

Evaluation of Oncoxin-Viusid® in Cutaneous Melanoma

Evaluation of the Nutritional Supplement Oncoxin-Viusid® in the Treatment of 20 Patients With Cutaneous Melanoma in Stage IIB-IIIA

Calculated according to the method of Kaplan Meyer

Calculated according to the Kaplan Meyer method

Quality of life questionnaire of the EORTC: QLQ30

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Efficacy and Safety of Nintedanib Combined With Paclitaxel Chemotherapy for Patients With BRAF wt Metastatic Melanoma	NCT02308553	Cutaneous Malig...	Nintedanib Nintedanib-Plac... Paclitaxel	18 Years -	University Hospital, Essen
Electrochemotherapy Induces Changes in the Tumor Microenvironment of Cutaneous and Subcutaneous Metastases in Patients With Cutaneous Melanoma	NCT06388252	Cutaneous Malig...	Electrochemothe... Electrochemothe...	18 Years - 100 Years	Institute of Oncology Ljubljana
Vitamin D Supplementation in Cutaneous Malignant Melanoma Outcome	NCT01748448	Cutaneous Malig...	Vitamin D arachides oleum...	18 Years - 80 Years	Universitaire Ziekenhuizen KU Leuven
Comparative Microarray Analysis in Primary Cutaneous Malignant Melanoma	NCT01482260	Cutaneous Malig...	Biopsy	1 Year -	Ruhr University of Bochum
Low-Dose-Rate Brachytherapy Combined With Immune Checkpoint Inhibition in Cancer	NCT04620603	Cutaneous Malig... Renal Cell Canc... Urothelial Canc...	Low Dose Rate B... Standard-of-Car...	18 Years -	Case Comprehensive Cancer Center
Tailored Intervention for Melanoma Patient's Families	NCT00816374	Melanoma	Reading materia... Reading materia... Questionnaires	21 Years -	Fox Chase Cancer Center
Evaluation of Oncoxin-Viusid® in Cutaneous Melanoma	NCT03541148	Cutaneous Melan... Malignant Cutan... Cutaneous Melan...	Oncoxin-Viusid	18 Years -	Catalysis SL

Spots Global Cancer Trial Database for cutaneous malignant melanoma