Metastatic MelanomaEXOSOMESNCT02310451
Study of Molecular Mechanisms Implicated in the Pathogenesis of Melanoma. Role of Exosomes
A study testing blood test in people with Metastatic Melanoma, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
Trial summary
Recent progresses have been made in the treatment of metastatic melanoma, nevertheless improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve the… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Metastatic Melanoma
- What is being tested?
- blood test
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteFrance
- Study dates
- Dec 2014to 31 Jul 2023
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Subject of both sexes at least 18 years of age
- Patient with advanced melanoma unresectable (stage IIIc) or metastatic (stage IV)
- Patient for whom is considered a systemic treatment by BRAF inhibitor
- Patient no previously treated or no responding to chemotherapy with a last injection> 1month
- Patient affected by a melanoma measurable according to version 1.1 of RECIST criteria
- Patient with a life expectancy superior than 3 months
Show all 11Show fewer
- Serum pregnancy test negative for all women of childbearing age
- ECOG ≤1
- Patient affiliated to French social security
- Patient able to understand and communicate with the investigator and to comply with the requirements of the study
- Patient must give a written, signed and dated informed consent before any study related activity is performed. Where relevant, a legal representative will also sign the informed study consent according to local laws and regulations
Who cannot join
- Patients not eligible to a BRAF inhibitor therapy or affected by a serious disease wich could require a treatment susceptible to interfere with melanoma treatment
- Pregnant and lactating women
- Patient with active malignancy or a previous malignancy within the past 3 years; except for patient with resected BCC, resected cutaneous SCC, resected carcinoma in-situ of the cervix, and resected carcinoma in-situ of the breast
- Past medical history record of infection with human immunodeficiency virus or viral hepatite C or B
- Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Pilot Study of Exosomes Before and After BRAF Inhibitor Therapy in Patients With Advanced Unresectable or Metastatic BRAF Mutation-positive Melanoma
Recent progresses have been made in the treatment of metastatic melanoma, nevertheless improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve the management of patients.
Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. It is now known that senescent cells secrete some factors that exert a pro-tumoral role but the potential existence and the role of insoluble factors remain undetermined.
Read more
Preliminary results from the investigators laboratory indicate the presence in the senescent secretome of exosomes; microvesicles involved in intercellular communication, immunomodulatory functions, and tumorigenesis. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells.
Their interest in oncology as a prognostic factor and marker of therapeutic response is increasing.
Thus, our project aims to study the effect of exosomes produced by senescent melanoma cells in the development and progression of melanoma in vitro and in vivo using cell cultures and animal models.
In addition, the investigator propose a pilot study whose objective is to determine the effect of vemurafenib on nanovesicles produced by patients with advanced unresectable or metastatic melanoma.
The investigator hope to show that exosomes participate in the process of drug resistance and relapse, with the goal of developing (with the exosomes study) theranostic tools for personalized care in patients.
Read the detailed description
Metastatic melanoma is an aggressive tumor with a 5-year survival rate of about 6 months. Although recent progresses have been made in the treatment of metastatic melanoma, improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve current treatments and / or to discover new anti-metastatic melanoma treatments.
Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. Although senescence is a process that limits the proliferation of cells, it is now known that senescent cells secrete factors that exert a pro-tumoral role. If many studies have focused on the role of the soluble factors of this secretome, the potential existence and the role of insoluble factors remain undetermined. Preliminary results from the investigators laboratory indicate the presence in the senescent secretome of exosomes; microvesicles involved in intercellular communication, immunomodulatory functions, and tumorigenesis. The exovesicules discharged by a cell in its environment are the subject of increasing interest in oncology as a prognostic factor and marker of therapeutic response. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells.
This project aims to study the effect of exosomes produced by senescent melanoma cells in the development and progression of melanoma in vitro and in vivo using cell cultures and animal models. In addition, the investigator propose a pilot study whose objective is to determine the effect of vemurafenib on production, quantity, size and composition of nanovesicles produced by patients with advanced unresectable or metastatic melanoma. The investigator hope to show that exosomes participate in the process of drug resistance and relapse, with the goal of developing (with the exosomes study) theranostic tools for personalized care in patients.
- Conditions
- Metastatic Melanoma
- Being tested
- blood test
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
blood testBiological
blood test to J0-M3-M6-M12
| Study group | Role | What they receive |
|---|---|---|
| metastatic melanoma | Experimental | Patients affected by advanced melanoma not resectable (stage IIIc) or metastatic (stage IV) Receives: Biological: blood test |
What is being measured
The primary outcome is the main question the study is designed to answer.
number of exosomes
Measure of the number of exosomes (µg of proteins or particles)/ml in peripheral blood by differential ultracentrifugation before and after treatment.
Measured: change from Day 0 at Month12
Secondary outcomes (3)
number of patient with a detection test of exosomes positive measured
Calculation of number of patients with a detection test of exosomes positive measured in the peripheral blood after differential ultracentrifugation by protein assay and Nanosight before and after treatment.
Measured: change from Day 0 at Month12
survival
Difference in survival (overall survival and progression frre-survival) between patients depending on the size and number of exosomes (µg of proteins or particles)/ml before and after treatment, according to the method of Kaplan Meier
Measured: Month 12
Tumoral response
Difference of tumoral response (RECIST criteria) between patients depending on variation of the number of exosomes (µg of proteins or particles)/ml, size and composition before and after treatment.
Measured: Month 12
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Dec 2014 (estimated)
- Study startDec 2014
- Primary completionDec 2015
- Study completion31 Jul 2023
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Metastatic MelanomaStudies of the same condition, open and under way.
- More trials run by Centre Hospitalier Universitaire de NiceThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centre Hospitalier Universitaire de Nice
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Henri MONTAUDIE, PH, Principal investigator, Centre Hospitalier Universitaire de Nice
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02310451
- Sponsor's protocol ID
- 14-AOI-10
- Acronym
- EXOSOMES
- Status last verified
- Sep 2023
- First submitted
- 13 Nov 2014
- Last updated
- 8 Sep 2023
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 8 Sep 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pilot Study of Exosomes Before and After BRAF Inhibitor Therapy in Patients With Advanced Unresectable or Metastatic BRAF Mutation-positive Melanoma
- ClinicalTrials.gov ID
- NCT02310451
- Acronym / sponsor ID
- EXOSOMES / 14-AOI-10
- Conditions
- Metastatic Melanoma
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Centre Hospitalier Universitaire de NiceUniversity, hospital or other
- Study start
- Dec 2014 (actual)
- Primary completion
- Dec 2015 (actual)
- Study completion
- 31 Jul 2023 (actual)
- First posted
- 8 Dec 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent progresses have been made in the treatment of metastatic melanoma, nevertheless improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve the management of patients.
Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. It is now known that senescent cells secrete some factors that exert a pro-tumoral role but the potential existence and the role of insoluble factors remain undetermined.
Preliminary results from the investigators laboratory indicate the presence in the senescent secretome of exosomes; microvesicles involved in intercellular communication, immunomodulatory functions, and tumorigenesis. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells.
Their interest in oncology as a prognostic factor and marker of therapeutic response is increasing.
Thus, our project aims to study the effect of exosomes produced by senescent melanoma cells in the development and progression of melanoma in vitro and in vivo using cell cultures and animal models.
In addition, the investigator propose a pilot study whose objective is to determine the effect of vemurafenib on nanovesicles produced by patients with advanced unresectable or metastatic melanoma.
The investigator hope to show that exosomes participate in the process of drug resistance and relapse, with the goal of developing (with the exosomes study) theranostic tools for personalized care in patients.
Detailed description
Metastatic melanoma is an aggressive tumor with a 5-year survival rate of about 6 months. Although recent progresses have been made in the treatment of metastatic melanoma, improved patient survival is still limited because of primary resistance and relapses. It is therefore important to continue to understand the molecular mechanisms involved in melanoma development and progression to improve current treatments and / or to discover new anti-metastatic melanoma treatments.
Drugs such as the alkylating agents (temozolomide and fotemustine) or vemurafenib trigger senescence-like phenotypes in melanoma cells. Although senescence is a process that limits the proliferation of cells, it is now known that senescent cells secrete factors that exert a pro-tumoral role. If many studies have focused on the role of the soluble factors of this secretome, the potential existence and the role of insoluble factors remain undetermined. Preliminary results from the investigators laboratory indicate the presence in the senescent secretome of exosomes; microvesicles involved in intercellular communication, immunomodulatory functions, and tumorigenesis. The exovesicules discharged by a cell in its environment are the subject of increasing interest in oncology as a prognostic factor and marker of therapeutic response. Several studies showed that these vesicles shape the tumor microenvironment and contribute to the migration of cancer cells.
This project aims to study the effect of exosomes produced by senescent melanoma cells in the development and progression of melanoma in vitro and in vivo using cell cultures and animal models. In addition, the investigator propose a pilot study whose objective is to determine the effect of vemurafenib on production, quantity, size and composition of nanovesicles produced by patients with advanced unresectable or metastatic melanoma. The investigator hope to show that exosomes participate in the process of drug resistance and relapse, with the goal of developing (with the exosomes study) theranostic tools for personalized care in patients.
Study design
- Primary purpose
- Screening
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| metastatic melanoma | Experimental | Biological: blood testPatients affected by advanced melanoma not resectable (stage IIIc) or metastatic (stage IV) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (11 listed)
- Subject of both sexes at least 18 years of age
- Patient with advanced melanoma unresectable (stage IIIc) or metastatic (stage IV)
- Patient for whom is considered a systemic treatment by BRAF inhibitor
- Patient no previously treated or no responding to chemotherapy with a last injection> 1month
- Patient affected by a melanoma measurable according to version 1.1 of RECIST criteria
Key exclusion criteria (5 listed)
- Patients not eligible to a BRAF inhibitor therapy or affected by a serious disease wich could require a treatment susceptible to interfere with melanoma treatment
- Pregnant and lactating women
- Patient with active malignancy or a previous malignancy within the past 3 years; except for patient with resected BCC, resected cutaneous SCC, resected carcinoma in-situ of the cervix, and resected carcinoma in-situ of the breast
- Past medical history record of infection with human immunodeficiency virus or viral hepatite C or B
- Any medical or psychiatric condition which, in the Investigator's opinion, would preclude the participant from adhering to the protocol or completing the study per protocol
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| blood testblood test to J0-M3-M6-M12 | Biological | metastatic melanoma |
Primary outcome
number of exosomes
Time frame: change from Day 0 at Month12
Measure of the number of exosomes (µg of proteins or particles)/ml in peripheral blood by differential ultracentrifugation before and after treatment.
3 secondary outcomes
number of patient with a detection test of exosomes positive measured
Time frame: change from Day 0 at Month12
survival
Time frame: Month 12
Tumoral response
Time frame: Month 12
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Sep 2023.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Henri MONTAUDIE, PH principal investigator
Centre Hospitalier Universitaire de Nice
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing blood test in people with Metastatic Melanoma, run by Centre Hospitalier Universitaire de Nice at 1 site in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 11 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 8 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
number of exosomes (time frame: change from Day 0 at Month12). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Sep 2023.