Phase I of Histone Deacetylase (HDAC) Inhibitor Panobinostat With Ipilimumab With Unresectable III/IV Melanoma
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|ClinicalTrials.gov Identifier: NCT02032810|
Recruitment Status : Active, not recruiting
First Posted : January 10, 2014
Results First Posted : July 2, 2019
Last Update Posted : July 2, 2019
|Condition or disease||Intervention/treatment||Phase|
|Melanoma Skin Cancer||Drug: Panobinostat Drug: Ipilimumab||Phase 1|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||17 participants|
|Intervention Model:||Sequential Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Phase 1 Study of HDAC Inhibitor Panobinostat (LBH 589) Administered in Combination With Ipilimumab in Subjects With Unresectable Stage III or Stage IV Melanoma|
|Actual Study Start Date :||January 7, 2014|
|Actual Primary Completion Date :||September 6, 2017|
|Estimated Study Completion Date :||December 2019|
Experimental: Dose Escalation
Dose Escalation of Panobinostat + Ipilimumab. Participants will be assigned to receive a certain dose of panobinostat (5, 10, 15, or 20 mg) along with a dose of ipilimumab of 3 mg per kg (mg/kg) of body weight.
Participants will be assigned to receive a certain dose of panobinostat (5, 10, 15, or 20 mg). The dose of panobinostat will depend on the time point the participant enters the study and the side effects of other participants already on the study.
Other Name: LBH 589
Dose of ipilimumab of 3 mg per kg (mg/kg) of body weight.
Other Name: BMS-734016
- Maximum Tolerated Dose (MTD) [ Time Frame: Up to 36 months ]
MTD and recommended Phase 2 dose (RP2D) of panobinostat (PAN), administered in combination with ipilimumab (IPI) in participants with unresectable Stage III or Stage IV melanoma.
The goal is to enroll up to 36 patients for determination of the MTD, but will be successfully concluded earlier if 12 patients are accrued at the dose determined to be the MTD, with 3 dose limiting toxicities (DLTs).
All participants who receive study any drug therapy will be evaluated for safety. Safety assessments will be based on medical review of adverse event reports and the results of vital sign measurements, physical examinations, and clinical laboratory tests. Triplicate 12-lead electrocardiograms (ECGs) will be collected prior to dosing on Day 1 of induction cycle 1. MTD of PAN in milligrams (mg), with IPI at 3 mg/kg.
- Immune Related Overall Response Rate (ORR) [ Time Frame: Up to 36 months ]Tumor response by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and immune-related Response Criteria (irRC). RECIST: Best overall response from start of treatment until disease progression/recurrence. Immune-related Complete Response (irCR): Complete disappearance of all tumor lesions for at least 4 weeks from date of documentation of irCR. Immune-related Partial Response (irPR): Sum of the products of the 2 largest perpendicular diameters of all index lesions, measured and captured as the Sum of Product of Diameters (SPD) baseline. Stable Disease (SD): Neither sufficient shrinkage to qualify for PR nor sufficient increase to qualify for Progressive Disease (PD), taking as reference the smallest sum longest diameter (LD) since the treatment started. Immune-related Progressive Disease (irPD): At least a 25% increase in the SPD of all index lesions and new measurable lesions (irSPD) over the nadir SPD calculated for the index lesions.
- Progression Free Survival (PFS) [ Time Frame: Up to 6 months ]Progression Free Survival (PFS): is defined for each participant as the time from first dosing to the first observation of disease progression or death due to any cause. If a subject has not progressed or died at the time of analysis, PFS will be censored on the date of the last disease assessment. PFS will be calculated by Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. Progressive Disease (PD) = 20% increase in the sum of the longest diameter of target lesions.
- Overall Survival (OS) [ Time Frame: 36 months ]Overall survival: The time from randomization until death from any cause.
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): NCT02032810
|United States, Florida|
|H. Lee Moffitt Cancer Center and Research Institute|
|Tampa, Florida, United States, 33612|
|Principal Investigator:||Nikhil Khushalani, M.D.||H. Lee Moffitt Cancer Center and Research Institute|