Malignant Skin Melanoma T0Phase 2NILOMELNCT01168050
Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas Stage III Unresectable Melanomas.
A Phase 2 study testing Nilotinib in people with Malignant Skin Melanoma T0 and Stage III Melanoma, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Malignant Skin Melanoma T0, Stage III Melanoma, Stage IV Melanoma
- What is being tested?
- Nilotinib
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 25 participants
- Where
- 1 siteFrance
- Study dates
- Jul 2010to Dec 2013
- Phase
- Phase 2
- 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
- Patients with histologically proven melanoma with either c-KIT mutation or C-KIT amplification (without BRAF or NRAS mutation)
- Unresectable primary or stage III or stage IV melanoma
- Measurable disease (RECIST)
- The inclusion of patients with primary tumor or metastasis accessible to sequential biopsies will be favored. If such lesions are present, biopsies are mandatory and not optional
- No more than 1 previous specific therapy excluding tyrosine kinase inhibitors. 4 weeks wash out will be needed after cytotoxic therapy , 12 weeks wash out after anti -CTLA4 therapy or any immunological treatment
- No radiotherapy within 4 weeks ; previously irradiated lesion will not be considered as measurable unless progression at inclusion
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- ECOG performance status < 2
- WBC ≥ 3,000/mm³
- PNN ≥ 1,500/mm³ (G-CSF allowed)
- platelets ≥ 100,000/mm³
- Hb ≥ 9.0 g/dL ( transfusions allowed as well as recombinant erythropoetin)
- Creatinin clearance > 40ml/mn
- Normal kalemia
- Normal magnesemia
- Total bilirubin <1.5N ; ASAT and ALAT <2.5N
- PT/INR and PTT normal
- NYHA class < 3
- Signed Written Informed Consent
- Affiliated to the National Health Insurance
Who cannot join
- Patients refusal
- Age < 18 years
- Fertile women who do not want or cannot use effective contraception during the study and up to 8 weeks after the end of study
- Women pregnant or nursing
- Women with positive pregnancy test at inclusion or before treatment initiation
- Fertile and sexually active men whose partner are fertile women who do not use effective contraception
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- Clinical and/or radiographic evidence of active cerebral metastases
- Severe evolutive infection
- Known HIV infection
- Concomitant therapy with any other anti-cancer, immunomodulator or immunosuppressing agent or radiotherapy (except palliative care if bone metastases, after acceptance of principal investigator).
- Previous use of tyrosine kinase inhibitors
- More than one line of prior systemic therapies of melanoma by anti-cancer agent or immunotherapy.
- Received experimental treatment within 4 weeks of inclusion
- Pace-maker
- Cardiac dysfunction, as evaluated by one of:
- Ejection fraction < 45% (less than 28 days from inclusion)
- Congenital prolonged QT
- QTc > 450 ms
- Ventricular tachyarrhythmia within the past 6 months
- Bradycardia at rest < 50/mn
- Major conduction dysfunction
- Myocardial infarction within the previous 6 months
- Unstable angina
- Uncontrolled hypertension
- Digestive disease that may inhibited NILITINIB absorption
- Concomitant medication that may increase QT
- Taking CYP3A4 inhibitors
- Eating Sevilla oranges (or Sevilla oranges derivates), grapefruit (or grapefruit juice), grapes (or grapes juice), pomegranate (or pomegranate juice)
- Hereditary galactose intolerance, Lapp-lactase deficiency or glucose-galactose malabsorption.
Trial locations and contacts
1 site in 1 country.
France1 site, 1 recruiting
- Recruiting
Hôpital Saint-Louis
Paris, 75010
Celeste Lebbe, MD, PhD, celeste.lebbe@sls.aphp.fr
Celeste Lebbe, MD, PhD
About this study
Official title: Phase II Multicentric Uncontrolled National Trial Assessing the Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas , Stage III Unresectable Melanomas, or Stage IV Melanomas With c-KIT Mutation or Amplification.
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification. The primary objective is overall response rate (partial and complete response) according to RECIST 1.1 criteria, assessed using CT-SCAN (stage IV melanoma) or MRI (unresectable melanoma) after 6 months therapy with Nilotinib 800 mg/d. Secondary objectives include:
- Disease control rate (complete, partial response and stable disease)
- Metabolic response
- Tolerance NCI CTCAE Version 3.0
- Biomarkers associated to response and disease control.
Read the detailed description
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification (in case of c-KIT amplification, no B-RAF nor N-Ras mutation should be detected). The primary objective is overall response rate (partial and complete response) according to RECIST 1.1 criteria, assessed using CT-SCAN (stage IV melanoma) or MRI (unresectable melanoma) after 6 months therapy with Nilotinib 800 mg/d. Secondary objectives include:
- Disease control rate (complete, partial response and stable disease) according to RECIST
- Metabolic response rate (TEP-SCAN)
- Tolerance NCI CTCAE Version 3.0
- Biomarkers associated to response and disease control (evaluated at M0, M1 and M6). Protein analysis of c-KIT, PI3K, MAPK and STAT signalling pathways as well as PDGFR and Ephrin signalling pathways.
Patients with progressive disease after 3 months therapy will be withdrawn. Patient with stable disease after 3 months will continue Nilotinib until evaluation at 6 months. Patients with stable disease or progressive disease at 6 months will continue Nilotinib until progression.
The trial has been planned using a one-stage design (Fleming TR) . We considered that a response rate under 7.5% would define the null hypothesis of no efficacy . To detect a response rate of 30% or more with power 90% using a one-sided test at the 0.05 level, 25 patients have to be recruited.
Accrual for 2.5 years total study duration: 3 years
- Being tested
- Nilotinib
- Keywords
- Malignant Skin Melanoma T0, stage III unresectable melanomas,, or stage IV melanomas with c-KIT mutation, or amplification.
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Nilotinib 400 mg twice per day
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | Not described Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
Objective response
Partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 6 months
Secondary outcomes (4)
Disease control
Complete or partial response or stable disease per Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 6 months
Objective response
Partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST).
Measured: 3 months
Metabolic response
Metabolic response as evaluated by TEP-SCAN
Measured: 6 months
Tolerance
Tolerance will be evaluated according to National Cancer Institute (NCI) Criteria for Adverse Events, CTCAE v3.0
Measured: 1 year
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jul 2010 (estimated)
- Study startJul 2010
- Primary completionDec 2013 (estimated)
- Study completionDec 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Malignant Skin Melanoma T0Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 2
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 25 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Investigators
- Celeste Lebbe, MD, PhD, Principal investigator, Hôpital Saint-Louis, Paris, France
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01168050
- Sponsor's protocol ID
- P081237
- Acronym
- NILOMEL
- Status last verified
- Feb 2011
- First submitted
- 21 Jul 2010
- Last updated
- 8 Feb 2011
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 8 Feb 2011. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Phase II Multicentric Uncontrolled National Trial Assessing the Efficacy of Nilotinib in First or Second Line Treatment of Primary Melanomas , Stage III Unresectable Melanomas, or Stage IV Melanomas With c-KIT Mutation or Amplification.
- ClinicalTrials.gov ID
- NCT01168050
- Acronym / sponsor ID
- NILOMEL / P081237
- Keywords
- Malignant Skin Melanoma T0, stage III unresectable melanomas,, or stage IV melanomas with c-KIT mutation, or amplification.
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 25 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- Jul 2010
- Primary completion
- Dec 2013 (estimated)
- Study completion
- Dec 2013 (estimated)
- First posted
- 22 Jul 2010 (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.
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification. The primary objective is overall response rate (partial and complete response) according to RECIST 1.1 criteria, assessed using CT-SCAN (stage IV melanoma) or MRI (unresectable melanoma) after 6 months therapy with Nilotinib 800 mg/d. Secondary objectives include:
- Disease control rate (complete, partial response and stable disease)
- Metabolic response
- Tolerance NCI CTCAE Version 3.0
- Biomarkers associated to response and disease control.
Detailed description
NILOMEL is a phase II multicentric uncontrolled open national trial assessing the efficacy of Nilotinib in first or second line treatment of primary melanomas , stage III unresectable melanomas, or Stage IV melanomas with c-KIT mutation or amplification (in case of c-KIT amplification, no B-RAF nor N-Ras mutation should be detected). The primary objective is overall response rate (partial and complete response) according to RECIST 1.1 criteria, assessed using CT-SCAN (stage IV melanoma) or MRI (unresectable melanoma) after 6 months therapy with Nilotinib 800 mg/d. Secondary objectives include:
- Disease control rate (complete, partial response and stable disease) according to RECIST
- Metabolic response rate (TEP-SCAN)
- Tolerance NCI CTCAE Version 3.0
- Biomarkers associated to response and disease control (evaluated at M0, M1 and M6). Protein analysis of c-KIT, PI3K, MAPK and STAT signalling pathways as well as PDGFR and Ephrin signalling pathways.
Patients with progressive disease after 3 months therapy will be withdrawn. Patient with stable disease after 3 months will continue Nilotinib until evaluation at 6 months. Patients with stable disease or progressive disease at 6 months will continue Nilotinib until progression.
The trial has been planned using a one-stage design (Fleming TR) . We considered that a response rate under 7.5% would define the null hypothesis of no efficacy . To detect a response rate of 30% or more with power 90% using a one-sided test at the 0.05 level, 25 patients have to be recruited.
Accrual for 2.5 years total study duration: 3 years
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nilotinib | Experimental | Drug: Nilotinib |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (19 listed)
- Patients with histologically proven melanoma with either c-KIT mutation or C-KIT amplification (without BRAF or NRAS mutation)
- Unresectable primary or stage III or stage IV melanoma
- Measurable disease (RECIST)
- The inclusion of patients with primary tumor or metastasis accessible to sequential biopsies will be favored. If such lesions are present, biopsies are mandatory and not optional
- No more than 1 previous specific therapy excluding tyrosine kinase inhibitors. 4 weeks wash out will be needed after cytotoxic therapy , 12 weeks wash out after anti -CTLA4 therapy or any immunological treatment
Key exclusion criteria (29 listed)
- Patients refusal
- Age < 18 years
- Fertile women who do not want or cannot use effective contraception during the study and up to 8 weeks after the end of study
- Women pregnant or nursing
- Women with positive pregnancy test at inclusion or before treatment initiation
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 |
|---|---|---|
| NilotinibNilotinib 400 mg twice per day | Drug | Nilotinib |
Primary outcome
Objective response
Time frame: 6 months
Partial or complete response per Response Evaluation Criteria in Solid Tumors (RECIST).
4 secondary outcomes
Disease control
Time frame: 6 months
Objective response
Time frame: 3 months
Metabolic response
Time frame: 6 months
Tolerance
Time frame: 1 year
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 8 Feb 2011.
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.
Celeste Lebbe, MD, PhD principal investigator
Hôpital Saint-Louis, Paris, France
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Nilotinib in people with Malignant Skin Melanoma T0 and Stage III Melanoma, run by Assistance Publique - Hôpitaux de Paris 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 19 inclusion and 29 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: status not confirmed, as of the sponsor's last update on 8 Feb 2011. 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.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Zakia Idir, PhD (+33 1 4484 1747, zakia.idir@sls.aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Objective response (time frame: 6 months). 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 Feb 2011.