HD IL-2 + Vemurafenib in Patients With BRAF Mutation Positive Metastatic Melanoma (PROCLIVITY01)
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|ClinicalTrials.gov Identifier: NCT01683188|
Recruitment Status : Terminated (slow accrual led to early closure.)
First Posted : September 11, 2012
Last Update Posted : February 1, 2021
|Condition or disease||Intervention/treatment||Phase|
|Metastatic Melanoma||Drug: vemurafenib + HD IL-2||Phase 4|
This will be an open-label, uncontrolled two-arm, multi-center study in patients with metastatic melanoma with BRAFV600 oncogene mutations. Patients will initially receive treatment with vemurafenib interspersed with two courses of High Dose IL-2 (HD IL-2). Patients are eligible for the study if they have melanoma positive for the BRAFV600 mutation, have been on vemurafenib therapy for 0-18 weeks, have responding or stable disease if on vemurafenib, and meet the requirements for dosing with HD IL-2 and all protocol inclusion and exclusion criteria.
Two Cohorts will be enrolled, differing only in how they are characterized prior to HD IL-2 treatment:
Cohort 1: will consist of 135 patients naïve to vemurafenib and HD IL-2 therapy. Patients in Cohort 1 will have an initial evaluation and receive a defined 6 (± 1) week course of vemurafenib before beginning HD IL-2. This Cohort will be used to define study size and statistical validity with the comparator being historic controls (using data from the BRAF positive patients from the Melanoma SELECT study Protocol IIT10PLK06).
Cohort 2: will consist of up to 50 patients who have been on vemurafenib therapy for >7 to 18 weeks with stable or responding disease before starting HD IL-2. Patients in Cohort 2 will have an initial evaluation and will begin HD IL-2 treatment after >7 to 18 weeks of treatment with vemurafenib. This Cohort is designed to evaluate whether additive or synergistic clinical benefit or toxicity is observed in BRAFV600 mutation positive metastatic melanoma patients treated with vemurafenib as a single agent for >7 to18 weeks prior to the first course of HD IL-2 therapy in conjunction with continued vemurafenib.
Patients in both cohorts will discontinue dosing vemurafenib prior to each treatment with HD IL-2 and resume dosing after each discharge. Patients will receive up to two courses (four cycles) of HD IL-2 and will be evaluated for their disease responses at 10 weeks (±3 weeks) from the start of HD IL-2 dosing, and 26 weeks (±3 weeks) from the start of HD IL-2 dosing. QTc intervals will be reviewed daily for changes during each cycle of HD IL-2 dosing.
Administration of vemurafenib and HD IL-2 will be according to the respective Package Inserts and according to the Institution's standard of care. The investigator will determine the number of HD IL-2 cycles each patient will receive, according to the investigator's discretion and medical judgment.
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||53 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||A Multi-Center Study of High Dose Aldesleukin (Interleukin-2) + Vemurafenib Therapy in Patients With BRAFV600 Mutation Positive Metastatic Melanoma|
|Study Start Date :||August 2012|
|Actual Primary Completion Date :||November 2014|
|Actual Study Completion Date :||November 2014|
Patients who have received less than 7 weeks vemurafenib dosing prior to treatment with HD IL-2
Drug: vemurafenib + HD IL-2
Other Name: Proleukin
Patients who have receive >7 weeks to 18 weeks vemurafenib dosing prior to treatment with HD IL-2
Drug: vemurafenib + HD IL-2
Other Name: Proleukin
- Assess Complete Response (CR) rate in BRAFV600 mutation positive metastatic melanoma patients who have received vemurafenib plus HD IL-2 at 10 (±3) weeks from the start of HD IL-2 dosing to assess initial response and 26 (±3) weeks to assess and change [ Time Frame: 10 weeks, 26 weeks ]assessment of tumor response in patients with CR or near CR (> 90%) after discontinuation of vemurafenib, based on RECIST criteria
- compare safety between patients treated with vemurafenib and HD IL-2 versus historical HD IL-2 alone [ Time Frame: through study completion, an average of 1 year ]incidence of adverse events
- Compare PFS [ Time Frame: 1 year ]compare progression free survival (PFS) from initiation of vemurafenib between Cohort 1 and Cohort 2 patients, compare overall PFS with the historical data using vemurafenib or HD IL-2 alone,
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): NCT01683188
|Principal Investigator:||Tharak Rao, MD||Prometheus Laboratories|