Mucosal Lentiginous MelanomaPhase 2NCT00788775
Nilotinib in TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral, or Chronically Sun Damaged Melanoma
A Phase 2 study testing Nilotinib in people with Mucosal Lentiginous Melanoma and Acral Melanoma, run by Dana-Farber Cancer Institute at 8 sites in United States.
Trial summary
Given the poor prognosis and limited treatment options available for patients with mucosal or acral/lentiginous melanomas who develop metastatic disease, genetic discoveries of KIT mutations in these cancers present the need to test multi-targeted kinase inhibitors with potent KIT inhibitory activity in this patient… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Mucosal Lentiginous Melanoma, Acral Melanoma, Melanoma
- What is being tested?
- Nilotinib
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 8 sitesUnited States
- Study dates
- 23 Jan 2009to Mar 2014
- Phase
- Phase 2
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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
- 18 years of age or older
- Histologically documented diagnosis of mucosal melanoma or acral melanoma or chronically sun damaged melanoma as evidenced by solar elastosis on pathology
- Patient's tumor with evidence for KIT mutation or amplification. Patient tumors that already have documented mutations or amplification do not have to have tissue submitted again for analysis to confirm eligibility
- Have failed, progressed, or not been able to tolerate other tyrosine kinase inhibitors including but not limited to imatinib mesylate, sunitinib or dasatinib treatment.
- At least one measurable site of disease
- ECOG Performance Status 0, 1 or 2
- Adequate organ function as outlined in the protocol
- Negative pregnancy test for female patients of childbearing potential
Who cannot join
- Patient has received any other investigational agents within 28 days of first day of study drug dosing unless the disease is rapidly progressing
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ
- Female patients who are pregnant or breast-feeding
- Patient has a severe and/or uncontrolled medical disease
- Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption
- Patient with electrolyte abnormality unless the level can be corrected to normal levels prior to initiating study drug
Show all 19Show fewer
- Known brain metastasis
- Known chronic liver disease
- Patient has received chemotherapy within 4 weeks prior to study entry, unless the disease is rapidly progressing (6 weeks for nitrosourea or mitomycin-C)
- Patient previously received radiotherapy to 25% or greater of the bone marrow
- Patient had a major surgery within 2 weeks prior to study entry
- Impaired cardiac function
- QTc > 450msec on screening ECG
- Myocardial infarction within one year prior to starting nilotinib
- Other clinically significant heart disease
- Patients who are currently receiving treatment with any of the medications that have the potential to prolong QT interval
- Patients who are currently receiving Warfarin > 1mg/day
- Patient with any significant history of non-compliance to medical regimens or with the inability to grant reliable informed consent
- Prior therapy with nilotinib
Trial locations and contacts
8 sites in 1 country.
8 sites in 1 country
United States8 sites
University of Colorado
Aurora, Colorado, 80045
Massachusetts General Hospital
Boston, Massachusetts, 02114
Dana-Farber Cancer Institute
Boston, Massachusetts, 02115
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
University of Chicago
Chicago, Illinois, 60637
Memorial Sloan Kettering Cancer Center
New York, New York, 10065
The Angeles Clinic and Research Institute
Santa Monica, California, 90404
Moffitt Cancer Center
Tampa, Florida, 33612
About this study
Official title: A Phase II Study of Nilotinib (AMN107) In TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral or Chronically Sun Damaged Melanoma
Given the poor prognosis and limited treatment options available for patients with mucosal or acral/lentiginous melanomas who develop metastatic disease, genetic discoveries of KIT mutations in these cancers present the need to test multi-targeted kinase inhibitors with potent KIT inhibitory activity in this patient population. Imatinib and other tyrosine kinase inhibitors (TKIs) have the potential to be effective in this patient population, but patients may develop resistance to treatment. Therefore, in this study, we propose to test nilotinib in patients with metastatic mucosal, acral, or chronically sun-damaged melanoma following treatment with another TKI.
Read the detailed description
OBJECTIVES:
Primary
- To estimate the proportion of patients, with metastatic mucosal, acral, or chronically sun damaged melanomas, whose tumors have KIT aberrations, and who progressed or could not tolerate a KIT targeting tyrosine kinase inhibitor (TKI) (e.g. including but not limited to imatinib mesylate, sunitinib, or dasatanib), who are alive and without progression of disease four months after beginning treatment with nilotinib.
Secondary
- To determine early evidence of biologic and clinical activity by best overall response rate.
- To estimate time to progression of disease and overall survival.
- To determine the tolerability of nilotinib.
- To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
- To correlate c-kit mutational status and amplification status with response to therapy.
- To evaluate the feasibility of nilotinib.
- To evaluate the tolerability of nilotinib in patients with brain metastases.
- Conditions
- Mucosal Lentiginous Melanoma, Acral Melanoma, Melanoma
- Being tested
- Nilotinib
- Keywords
- nilotinib
- Medical subject headings
- Melanoma
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
NilotinibDrug
Also called Tasigna, AMN107
| Study group | Role | What they receive |
|---|---|---|
| Nilotinib | Experimental | Nilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. Receives: Drug: Nilotinib |
What is being measured
The primary outcome is the main question the study is designed to answer.
4-month Progression-Free Survival Rate
4-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Measured: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 4 months.
Secondary outcomes (3)
Progression-Free Survival
Progression-free survival (PFS) based on the Kaplan-Meier method is defined as the duration of time from study entry to documented disease progression (PD) requiring removal from the study or death. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
Measured: Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).
Overall Survival
Overall survival (OS) is defined as the time from study entry to death or date last known alive.
Measured: Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 16.2 months (90%CI 11.7-17.7 months; no/with CNS mets 16.2m/ 11.7m).
Best Overall Response
Best overall response (BOR) on treatment was based on RECIST 1.0 criteria. For target lesions, complete response (CR) is complete disappearance of all target lesions and partial response (PR) is at least a 30% decrease in the sum of longest diameter (LD) of target lesions, taking as reference baseline sum LD. CR or PR confirmation required within 4 weeks. Progressive disease (PD) is at least a 20% increase in the sum LD of target lesions from smallest sum LD as reference or the appearance of one or more new lesions. Stable disease (SD) is neither meeting PR or PD. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions. CR is disappearance of all non-target lesions.
Measured: Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted11 Nov 2008 (estimated)
- Study start23 Jan 2009
- Primary completionApr 2011
- Study completionMar 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Mucosal Lentiginous MelanomaStudies of the same condition, open and under way.
- More trials run by Dana-Farber Cancer InstituteThe 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
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Dana-Farber Cancer Institute
- Sponsor type
- University, hospital or other
- Collaborators
- Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Novartis
- Responsible party
- Principal investigator, F. Stephen Hodi, MD, Dana-Farber Cancer Institute
- Investigators
- F. Stephen Hodi, MD, Principal investigator, Dana-Farber Cancer Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00788775
- Sponsor's protocol ID
- 08-244
- Status last verified
- Oct 2018
- First submitted
- 10 Nov 2008
- Last updated
- 15 Nov 2018
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Publications
Carvajal RD, Lawrence DP, Weber JS, Gajewski TF, Gonzalez R, Lutzky J, O'Day SJ, Hamid O, Wolchok JD, Chapman PB, Sullivan RJ, Teitcher JB, Ramaiya N, Giobbie-Hurder A, Antonescu CR, Heinrich MC, Bastian BC, Corless CL, Fletcher JA, Hodi FS. Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition. Clin Cancer Res. 2015 May 15;21(10):2289-96. doi: 10.1158/1078-0432.CCR-14-1630. Epub 2015 Feb 18.
PubMed 25695690
Study at a glance
From the registry record, last updated by the sponsor on 15 Nov 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase II Study of Nilotinib (AMN107) In TKI Resistant or Intolerant Patients With Metastatic Mucosal, Acral or Chronically Sun Damaged Melanoma
- ClinicalTrials.gov ID
- NCT00788775
- Acronym / sponsor ID
- 08-244
- Conditions
- Mucosal Lentiginous Melanoma, Acral Melanoma, Melanoma
- Keywords
- nilotinib
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Dana-Farber Cancer InstituteUniversity, hospital or other
- Collaborators
- Brigham and Women's Hospital, Beth Israel Deaconess Medical Center, Massachusetts General Hospital, Novartis
- Study start
- 23 Jan 2009 (actual)
- Primary completion
- Apr 2011 (actual)
- Study completion
- Mar 2014 (actual)
- First posted
- 11 Nov 2008 (estimated)
- Results
- Posted 8 Dec 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Given the poor prognosis and limited treatment options available for patients with mucosal or acral/lentiginous melanomas who develop metastatic disease, genetic discoveries of KIT mutations in these cancers present the need to test multi-targeted kinase inhibitors with potent KIT inhibitory activity in this patient population. Imatinib and other tyrosine kinase inhibitors (TKIs) have the potential to be effective in this patient population, but patients may develop resistance to treatment. Therefore, in this study, we propose to test nilotinib in patients with metastatic mucosal, acral, or chronically sun-damaged melanoma following treatment with another TKI.
Detailed description
OBJECTIVES:
Primary
- To estimate the proportion of patients, with metastatic mucosal, acral, or chronically sun damaged melanomas, whose tumors have KIT aberrations, and who progressed or could not tolerate a KIT targeting tyrosine kinase inhibitor (TKI) (e.g. including but not limited to imatinib mesylate, sunitinib, or dasatanib), who are alive and without progression of disease four months after beginning treatment with nilotinib.
Secondary
- To determine early evidence of biologic and clinical activity by best overall response rate.
- To estimate time to progression of disease and overall survival.
- To determine the tolerability of nilotinib.
- To evaluate the use of FDG-PET scanning in determining early biologic response to therapy.
- To correlate c-kit mutational status and amplification status with response to therapy.
- To evaluate the feasibility of nilotinib.
- To evaluate the tolerability of nilotinib in patients with brain metastases.
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: NilotinibNilotinib was given at a dose of 400 mg orally daily (200 mg pills twice per day). Patients received treatment up to 12 months as long as they were receiving clinical benefit. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 18 years of age or older
- Histologically documented diagnosis of mucosal melanoma or acral melanoma or chronically sun damaged melanoma as evidenced by solar elastosis on pathology
- Patient's tumor with evidence for KIT mutation or amplification. Patient tumors that already have documented mutations or amplification do not have to have tissue submitted again for analysis to confirm eligibility
- Have failed, progressed, or not been able to tolerate other tyrosine kinase inhibitors including but not limited to imatinib mesylate, sunitinib or dasatinib treatment.
- At least one measurable site of disease
Key exclusion criteria (19 listed)
- Patient has received any other investigational agents within 28 days of first day of study drug dosing unless the disease is rapidly progressing
- Patient is < 5 years free of another primary malignancy except: if the other primary malignancy is not currently clinically significant nor requiring active intervention, or if other primary malignancy is a basal cell skin cancer or a cervical carcinoma in situ
- Female patients who are pregnant or breast-feeding
- Patient has a severe and/or uncontrolled medical disease
- Patient has a rare hereditary problem of galactose intolerance, severe lactase deficiency or of glucose-galactose malabsorption
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 |
|---|---|---|
| NilotinibAlso: Tasigna, AMN107 | Drug | Nilotinib |
Primary outcome
4-month Progression-Free Survival Rate
Time frame: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 4 months.
4-month progression-free survival rate was defined as the proportion of patients absent death or progression based on Response Evaluation Criteria In Solid Tumors Criteria (RECIST) before 4 months. Per RECIST 1.0 criteria: progressive disease (PD) is at least a 20% increase in the sum of longest diameter (LD) of target lesions taking as reference the smallest sum LD recorded since the treatment started or the appearance of one or more new lesions. PD for the evaluation of non-target lesions is the appearance of one or more new lesions and/or unequivocal progression of non-target lesions.
3 secondary outcomes
Progression-Free Survival
Time frame: Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).
Overall Survival
Time frame: Patients were followed long-term every 3 months until first progression, death or lost to follow-up. Median survival follow-up was 16.2 months (90%CI 11.7-17.7 months; no/with CNS mets 16.2m/ 11.7m).
Best Overall Response
Time frame: Disease was evaluated radiologically at baseline and every 8 weeks on treatment and long-term every 3 months until first progression, death or lost to follow-up. Mean treatment duration was 5.5 months (range 0-45; no/with CNS mets 7.4m/ 3m).
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 15 Nov 2018.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Results publication: PubMed 25695690Carvajal RD, Lawrence DP, Weber JS, Gajewski TF, Gonzalez R, Lutzky J, O'Day SJ, Hamid O, Wolchok JD, Chapman PB, Sullivan RJ, Teitcher JB, Ramaiya N, Giobbie-Hurder A, Antonescu CR, Heinrich MC, Bastian BC, Corless CL, Fletcher JA, Hodi FS. Phase II Study of Nilotinib in Melanoma Harboring KIT Alterations Following Progression to Prior KIT Inhibition. Clin Cancer Res. 2015 May 15;21(10):2289-96. doi: 10.1158/1078-0432.CCR-14-1630. Epub 2015 Feb 18.
- Individual participant dataSharing planned: No
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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.
F. Stephen Hodi, MD principal investigator
Dana-Farber Cancer Institute
8 sites 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 Mucosal Lentiginous Melanoma and Acral Melanoma, run by Dana-Farber Cancer Institute at 8 sites in United States.
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 8 inclusion and 19 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 15 Nov 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in United States. 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?
Yes. Results are posted in the registry (first posted 8 Dec 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
4-month Progression-Free Survival Rate (time frame: Disease was evaluated radiologically at baseline and every 8 weeks on treatment; Treatment continued for 12 months unless disease progression or unacceptable toxicity. Relevant for this endpoint was disease status at 4 months.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00788775, which also lists 1 linked publication.
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 15 Nov 2018.