Adult unresectable metastatic melanoma patients either non pretreated or pretreated with B-Raf inhibitors or their combination with MEK inhibitors MedDRA version: 20.0 Level: LLT Classification code 10027481 Term: Metastatic melanoma System Organ Class: 100000004864
Conditions
Interventions
Trade Name: YERVOY - 5 MG/ML - CONCENTRATO PER SOLUZIONE PER INFUSIONE - USO ENDOVENOSO -
FLACONCINO (VETRO) - 40 ML 1 FLACONCINO
Product Name: IPILIMUMAB
Product Code: NA
Pharmaceutical Form: Concent
Sponsors
AZIENDA OSPEDALIERO-UNIVERSITARIA PISANA
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1 .Subjects capable of giving informed consent must have signed and dated an IRB/IEC approved written informed consent form in accordance with regulatory and institutional guidelines. This must be obtained before the performance of any protocol related procedures that are not part of normal subject care. 2. Subjects must be willing and able to comply with scheduled visits, treatment schedule, laboratory testing, and other requirements of the study. 3. Histologically confirmed unresectable Stage III or Stage IV melanoma, as per AJCC staging system. 4. Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 (Refer to Appendix 4) 5. Treatment naïve subjects (ie, no prior systemic anticancer therapy for unresectable or metastatic melanoma). Note that prior adjuvant or neoadjuvant melanoma therapy is permitted if it was completed at least 6 weeks prior to randomization, and all related adverse events have either returned to baseline or stabilized. 6. Measurable disease by CT or MRI per RECIST 1.1 criteria [89] 7. Tumor tissue from an unresectable or metastatic site of disease must be provided for disease diagnsis. 8. Subjects must have known BRAF V600 mutation status or consent to BRAF V600 mutation testing per local institutional standards during the Screening Period. 9. Prior radiotherapy must have been completed at least 2 weeks prior to study drug administration. 10. Screening laboratory values must meet the following criteria and should be obtained within 14 days prior to study entry: i) WBC = 2000/µL ii) Neutrophils = 1500/µL iii) Platelets =100 x103/µL iv) Hemoglobin = 9.0 g/dL v) Serum creatinine = 1.5 x ULN or creatinine clearance (CrCl) = 40 mL/min (using the Cockcroft-Gault formula): Female CrCl = (140 - age in years) x weight in kg x 0.85 72 x serum creatinine in mg/dL Male CrCl = (140 - age in years) x weight in kg x 1.00 72 x serum creatinine in mg/dL vi) AST/ALT = 3 x ULN vii) Total Bilirubin = 1.5 x ULN (except subjects with Gilbert Syndrome, who can have total bilirubin 18 years of age 12. Women of childbearing potential (WOCBP as defined below) and Men who are sexually active with WOCBP must use any contraceptive method with a failure rate of less than 1% per year as indicated in Appendix 5 for at least 6 and 7,5 months, respectively, after the last dose of investigational drug (see also 2014_09_HMA_CTFG_Contraception.pdf). 13. Subject must consent to undergo a biopsy of their metastasis for confirmation of the diagnosis and/or BRAF V600 mutational testing Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 50 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 10
Exclusion criteria
Exclusion criteria: 1.Active brain metastases or leptomeningeal metastases. Subjects with brain metastases are eligible if these have been treated and there is no magnetic resonance imaging (MRI) evidence of progression for at least 8 weeks after treatment is complete and within 28 days prior to first dose of study drug administration. There must also be no requirement for immunosuppressive doses of systemic corticosteroids (> 10 mg/day prednisone equivalents) for at least 2 weeks prior to study drug administration. 2.Ocular melanoma 3.Any serious or uncontrolled medical disorder that, in the opinion of the investigator, may increase the risk associated with study participation or study drug administration, impair the ability of the subject to receive protocol therapy, or interfere with the interpretation of study results. 4.Prior malignancy active within the previous 3 years except for locally curable cancers that have been apparently cured, such as basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the prostate, cervix, or breast. 5.Subjects with active, known or suspected autoimmune disease. Subjects with vitiligo, type I diabetes mellitus, residual hypothyroidism due to autoimmune condition only requiring hormone replacement, psoriasis not requiring systemic treatment, or conditions not expected to recur in the absence of an external trigger are permitted to enroll. 6.Subjects with a condition requiring systemic treatment with either corticosteroids (> 10 mg daily prednisone equivalents) or other immunosuppressive medications within 14 days of study drug administration. Inhaled or topical steroids, and adrenal replacement doses > 10 mg daily prednisone equivalents are permitted in the absence of active autoimmune disease. 7.Prior treatment with an anti-PD-1, anti-PD-L1, anti-PD-L2, anti-CTLA-4 antibody, or any other antibody or drug specifically targeting T-cell costimulation or immune checkpoint pathways, are permitted only under exceptional circumstances and always after PI approval. 8.Positive test for hepatitis B virus surface antigen (HBV sAg) or hepatitis C virus ribonucleic acid (HCV antibody) indicating acute or chronic infection, as determined in subjects where the condition is unknown at time of study entry. 9.Known history of testing positive for human immunodeficiency virus (HIV) or known acquired immunodeficiency syndrome (AIDS). 10.History of allergy to study drug components. 11.History of severe hypersensitivity reaction to any monoclonal antibody. 12.WOCBP who are pregnant or breastfeeding 13.Women with a positive pregnancy test at enrollment or prior to administration of study medication. 14.Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness Women of Childbearing Potential Women of childbearing potential (WOCBP) is defined as any female who has experienced menarche and who has not undergone surgical sterilization (hysterectomy or bilateral oophorectomy) or is not postmenopausal. Menopause is defined clinically as 12 months of amenorrhea in a woman over age 45 in the absence of other biological or physiological causes.In additional, women under the age of 62 must have a documented serum follicle stimulating hormone, (FSH) level > 40mIU/mL. Prohibited and/or Restricted Treatments The following medications are prohibited during the study: • Immunosuppressive agents (except to treat a drug-related adverse event) • Systemic corticost
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Primary end point(s): •Primary endpoints of the study will be measured by the endpoints of ORR, duration of Objective Response and Time to progression. The ORR is defined as the number of subjects with a BOR of CR or PR divided by the number of subjects included in the study. The BOR is defined as the best response designation, as determined by the investigator, recorded between the date of study entry and the date of objectively documented progression per RECIST 1.1 or the date of subsequent anti-cancer therapy, whichever occurs first. first. For subjects without documented progression or subsequent therapy, all available response designations will contribute to the BOR assessment. Tumor assessments are scheduled to be performed at Week 14, every 8 Weeks up to Week 52 and then every 12 Weeks until disease progression or for a maximum of 5 years. Duration of response will be measured by the endpoints duration of objective response (DOOR). DOOR is defined as the time between the date of first response to the date of first documented tumor progression (per RECIST 1.1) or death due to any cause. Subjects who neither progress nor die will be censored on the date of their last tumor assessment. DOOR will be evaluated for responders (CR or PR) only. •Response is defined by irCriteria and WHO criteria (table 1) [89]. Measurable disease is assessed by means of CT or MRI according to Response Evaluation Criteria in Solid Tumors (RECIST), version 1.1 [90] •Safety and tolerability will be measured by the incidence of adverse events, serious adverse events, deaths, and laboratory abnormalities. Toxicity will be evaluated according to ECOG criteria [91]. •Any patient who received at least one dose of study drug will be included in the assessment of safety. The severity of adverse events will be graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0 [90]. Safety assessments will be made continuously during the treatment phase | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): The first secondary objective will be measured by the endpoint of PFS. PFS is defined as the time between the date of study entry and the first date of documented progression, as determined by the investigator, or death due to any cause, whichever occurs first. Subjects who die without a reported progression will be considered to have progressed on the date of their death. Subjects who did not progress or die will be censored on the date of their last evaluable tumor assessment. Subjects who did not have any on study tumor assessments and did not die will be censored on their date of study entry. Subjects who started anti-cancer therapy without a prior reported progression will be censored on the date of their last evaluable tumor assessment prior to the initiation of subsequent anti-cancer therapy. Tumor assessments are scheduled to be performed at Week 14, every 8 Weeks up to Week 52 and then every 12 Weeks until disease progression for a maximum of 5 years. The second secondary objective will be measured by the endpoint of OS in all subjects entering the study. OS is defined as the time between the date of study entry and the date of death due to any cause. OS will be censored on the last date a subject was known to be alive. OS data will be collected continuously while subjects are on study medication and every 2 months up to 1 year and then every 3 months up to 5 years. • Time to progression (TTP) will be measured between the date of study entry and the date of first documented tumor progression (per RECIST 1.1) or death due to any cause. TTP will be evaluated for stable disease (SD). •B-Raf status will be determined prior to study entry to evaluate which treatment would be more appropriate for the patient and his/her clinical situation, in paraffin embedded tissue samples, stored for 10 years, per local institutional standards . B-Raf status will be correlated with ORR, PFS and OS. •Detection of wellbeing questionnaire will be administe | — |
Countries
Italy
Contacts
Public ContactU.O. Oncologia Medica 1
AZIENDA OSPEDALIERO - UNIVERSITARIA PISANA
Outcome results
None listed