Stage IV Melanoma MedDRA version: 14.0 Level: PT Classification code 10025671 Term: Malignant melanoma stage IV System Organ Class: 10029104 - Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Conditions
Interventions
Trade Name: YERVOY®
Product Name: Ipilimumab
Pharmaceutical Form: Concentrate for solution for infusion
Other descriptive name: Ipilimumab
Concentration unit: mg milligram(s)
Concentration type: equal
Sponsors
University Clinical Center of Tuebingen
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: • Willing and able to give written informed consent; • Histological diagnosis of malignant melanoma; • Stage IV melanoma; • At least one injectable lesions > 5 mm (longest diameter) or at least 5 injectable lesions =65 years) yes F.1.3.1 Number of subjects for this age range 20
Exclusion criteria
Exclusion criteria: • Any other prior malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer or carcinoma in situ of the cervix; • Ocular melanoma; mucosal melanoma • Either untreated or symptomatic central nervous system (CNS) metastases (patients with brain metastases who are identified at screening may be rescreened after the lesion(s) have been appropriately treated); • Autoimmune disease: Patients with a history of inflammatory bowel disease are excluded from this study, as are patients with a history of symptomatic autoimmune disease (e.g., rheumatoid arthritis, systemic progressive sclerosis [scleroderma], systemic lupus erythematosus, autoimmune vasculitis [e.g., Wegener’s Granulomatosis]); motor neuropathy considered of autoimmune origin (e.g., Guillain-Barre Syndrome). Patients with vitiligo may be included. • Any underlying medical or psychiatric condition, which in the opinion of the investigator will make the administration of ipilimumab hazardous or obscure the interpretation of AEs, such as a condition associated with frequent diarrhea. • Any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month before or after any dose of ipilimumab). • A history of prior systemic treatment with ipilimumab, CD137 agonist, CTLA 4 inhibitor, CTLA-4 agonist or IL-2 in stage IV melanoma. • Concomitant or less than 4 weeks off therapy with any of the following: interferon; other non-study immunotherapy regimens; cytotoxic chemotherapy; immunosuppressive agents; other investigation therapies; chronic use of systemic corticosteroids. • Women of childbearing potential (WOCBP), defined in Section 5.3, who: 1. are unwilling or unable to use an acceptable method of contraception to avoid pregnancy for their entire study period and for at least 26 weeks after cessation of study drug, or 2. have a positive pregnancy test at baseline, or 3. are pregnant or breastfeeding. • Subjects who are compulsorily detained for treatment of either a psychiatric or physical (e.g., infectious) illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: efficacy of the combined treatment with ipilimumab and intratumoral IL-2 based on the Disease Control Rate according to immune-related Response Criteria (irDCR) at week 12;Secondary Objective: • Tolerability according to NCI-CTCAE-Criteria (version 4) • Overall response rate (sum of irPR and irCR) at week 12 according to irRC • Overall survival after 12 months • Best overall responsei rate according to irRC (irBORR). • Overall Response Rate at week 12 and Best Overall Response Rate according to modified mWHO criteria ;Primary end point(s): Immune related Disease control rate (irDCR): sum of patients with an overall response irCR or irPR or irSD divided by the total number of patients, who are evaluable of efficacy. 95% confidence intervals will be provided. ;Timepoint(s) of evaluation of this end point: at week 12 | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Immune related Overall response rate at week 12 (irORR): sum of patients with an overall response irPR or irCR, divided by the total number of patients, who are evaluable of efficacy. 95% confidence intervals will be provided. Immune related Best overall response rate (irBORR): number of patients whose irBOR is CR or PR divided by the total number of patients, who are evaluable of efficacy. 95% confidence intervals will be provided. Response rate with regards to injected metastases only at week 12: sum of patients with CRinj or PRinj divided by the total number of patients with either CRinj, PRinj, SDinj or PDinj. 95% confidence intervals will be provided. Overall survival after 12 months: The calculation of the overall survival rate after 12 months (12 months after the first dose) will comprise all patients, who received at least one dose of study drug(s). It will be calculated using the Kaplan-Meier method. An event is defined as death from malignant melanoma. All other patients will be censored at the time point of his/her last follow-up within the context of this protocol. 95% confidence intervals for the estimated survival rate will be provided. Overall response rate at week 12 according to mWHO criteria: sum of patients with an overall response PR or CR according to mWHO criteria, divided by the total number of patients, who are evaluable of efficacy. 95% confidence intervals will be provided. Best overall response rate according to mWHO criteria: number of patients whose Best Overall Response is CR or PR according to mWHO criteria divided by the total number of patients, who are evaluable of efficacy. 95% confidence intervals will be provided. Clinical safety data will be analyzed by descriptive statistics for all patients, who received at least one dose of any investigational product within this protocol and attended at least once after dosing for adverse event assessment. The endpoints of optional translational side studies (rate of | — |
Countries
Germany
Outcome results
None listed