A Study of Fotemustine(FTM) Vs FTM and Ipilimumab (IPI) or IPI and Nivolumab in Melanoma Brain Metastasis (NIBIT-M2)
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|ClinicalTrials.gov Identifier: NCT02460068|
Recruitment Status : Recruiting
First Posted : June 2, 2015
Last Update Posted : June 2, 2015
|Condition or disease||Intervention/treatment||Phase|
|Brain Metastases||Drug: Fotemustine Drug: Fotemustine and Ipilimumab Drug: Ipilimumab and nivolumab||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||168 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Randomized, Phase III Study of Fotemustine Versus the Combination of Fotemustine and Ipilimumab or the Combination of Ipilimumab and Nivolumab in Patients With Metastatic Melanoma With Brain Metastasis|
|Study Start Date :||December 2012|
|Estimated Primary Completion Date :||January 2018|
|Estimated Study Completion Date :||January 2020|
Active Comparator: fotemustine
Fotemustine: fotemustine at 100 mg/mq intravenously (i.v.) over 60 minutes once every week for 3 doses, and once every 3 weeks from week 9 for 6 doses.
Other Name: Fotemustine (Muphoran);
Experimental: fotemustine and ipilimumab
fotemustine in combination with ipilimumab
Drug: Fotemustine and Ipilimumab
Fotemustine and ipilimumab:fotemustine 100 mg/m2 i.v. over 60 minutes once every week for 3 weeks (Weeks 1, 2, 3) plus ipilimumab at 10 mg/kg i.v. over 90 minutes every 3 weeks for 4 cycles (Weeks 1, 4, 7, 10); fotemustine 100 mg/m2 i.v. over 60 minutes once every 3 weeks from week 9 for 6 doses plus ipilimumab at 10 mg/kg i.v. over 90 minutes every 12 weeks from week 24.
Experimental: ipilimumab and nivolumab
ipilimumab in combination with nivolumab
Drug: Ipilimumab and nivolumab
ipilimumab and nivolumab: ipilimumab 3 mg/kg i.v over 90 minutes combined with nivolumab 1 mg/kg i.v over 60 minutes every three weeks for 4 doses, then nivolumab 3 mg/kg IV over 60 minutes every two weeks.
- Overall Survival (OS) [ Time Frame: 2 years ]To compare the efficacy of the combination of ipilimumab and fotemustine or the Combination of ipilimumab and nivolumab versus fotemustine in terms of overall survival (OS) in patients with metastatic melanoma with brain metastasis.Overall Survival (OS) is defined as the time from randomization until the date of death. For those subjects who have not died, OS will be censored at the recorded last date of subject contact, and for subjects with a missing recorded last date of contact, OS will be censored at the last date the subject was known to be alive.
- safety (adverse events) [ Time Frame: 2 years ]Reporting of safety, extent of exposure, concomitant medications and discontinuation of study therapy will be based on all treated subjects; for on-study laboratory test results, all treated subjects with at least one on-study laboratory measurement available will be included in the analysis. The reporting period for safety data will be from the date of first dose received on this study to 70 days (5 half-lives) after the last dose is received. Serious adverse events are reported from the time of consent forward for all subjects.All subjects who receive at least 1 dose of study treatment will be evaluated for safety parameters
- m-WHO and immune-related Disease Control Rate (DCR) in and outside the brain [ Time Frame: Weeks 24 ]m-WHO and immune-related is the proportion of treated subjects with a ir-BOR of confirmed irCR, confirmed irPR or irSD in and outside the brain.
- Immune-related Progression-free Survival (irPFS) [ Time Frame: 2 years ]Immune-related progression free survival (irPFS) per irRC will be defined as the time between the date of randomization and the date of progression per irRC or death, whichever occurs first. A subject who dies without reported progression per irRC will be considered to have progressed on the date of death.
- m-WHO Progression-free Survival (irPFS) [ Time Frame: 2 years ]Progression-free survival (PFS) per mWHO criteria will be defined as the time between the date of randomization and the date of progression per mWHO criteria or death, whichever occurs first. A subject who dies without reported progression per mWHO criteria will be considered to have progressed on the date of death.
- Objective Response Rate (ORR) [ Time Frame: Weeks 24 ]is the proportion of treated subjects with a BOR of confirmed CR or confirmed PR.
- Immune-related Objective Response Rate (irORR) [ Time Frame: Weeks 24 ]is the proportion of treated subjects with a irBOR of confirmed irCR or confirmed irPR.
- Time to Response (TTR) [ Time Frame: Weeks 24 ]Time to Response (TTR) is defined as the time from first dosing date until the measurement criteria are first met for overall response of PR or CR (whichever status comes first, and provided it is subsequently confirmed).
- Immune-related Time to Response (irTTR) [ Time Frame: Weeks 24 ]Immune-related Time to Response (irTTR) is defined as the time from first dosing date until the measurement criteria are first met for overall response of irPR or irCR (whichever status comes first, and provided it is subsequently confirmed).
- Duration of Response (DoR) [ Time Frame: 2 years ]Duration of Response (DoR) is defined as the time between the date the measurement criteria are first met for an CR or PR (whichever status comes first and provided it is subsequently confirmed) and the date of PD or death (whichever comes first). For a subject who undergoes tumor resection following response but prior to disease progression, DOR will be censored at the date of the last evaluable TA on or prior to the date of resection. For subjects who remain alive and have no progressive disease as assessed by the investigator using RC, DOR will be censored on the date of last evaluable tumor assessment.
- Immune-related Duration of Response (irDoR) [ Time Frame: 2 years ]Immune-related Duration of Response (irDoR) for the subjects whose irBOR is irCR or irPR will be defined as the time between the date of response of confirmed irCR or confirmed irPR (whichever occurs first) and the date of irPD or death (whichever occurs first). The onset of a confirmed irCR or irPR is determined by the initial assessment of response, not by the confirmatory assessment. Note that if an assessment of irPR occurs before confirmation of irCR, the duration of immune-related response endpoint will not begin at the time that the irBOR of irCR is shown but rather at the earlier time-point showing irPR. For subjects who remain alive and have not progressed following response, irDoR will be censored on the date of last evaluable TA.
- Brain progression-free survival (Brain-PFS) [ Time Frame: 6 months ]Brain progression-free survival (Brain-PFS) (3 and 6 months rates) is defined as the time from randomization date to the date of progression as per MRI of existing brain lesions, or of occurrence as per MRI of a new lesion located in the brain, or of death, whichever occurs first. For subjects who remain alive and have not progressed as per definition above, Brain-PFS will be censored at the day of last evaluable brain imaging assessment.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02460068
|Contact: Anna Maria Di Giacomo, PhD,MDemail@example.com|
|Contact: Michele Maio, PhD,MDfirstname.lastname@example.org|
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|Rome, Italy, 0014|
|Medical Oncology and Immunotherapy Unit, University Hospital of Siena||Recruiting|
|Siena, Italy, 53100|
|Contact: Anna Maria Di Giacomo, PhD,MD 0577 586305 email@example.com|
|Contact: Michele Maio, PhD,MD 0577 586335 firstname.lastname@example.org|
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|Turin, Italy, 10126|
|Contact: Pietro Quaglino, PhD, MD email@example.com|
|Principal Investigator:||Anna Maria Di Giacomo, PhD,MD||Medical Oncology and Immunotherapy Unit, University Hospital of Siena|