Subjects (men and women) 18 years old presenting with Stage IV melanoma with presence of brain metastasis MedDRA version: 14.1 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
Product Name: Ipilimumab
Product Code: BMS-734016
Pharmaceutical Form: Solution for infusion
INN or Proposed INN: IPILIMUMAB
CAS Number: 477202009
Current Sponsor code: BMS734016
Concentration unit: m
Sponsors
FONDAZIONE NIBIT
Eligibility
Sex/Gender
All
Inclusion criteria
Inclusion criteria: 1) Signed Written Informed Consent a) Willing and able to give written informed consent. 2) Target Population a) Histologic diagnosis of malignant melanoma; b) Stage IV melanoma; c) No prior therapy for advanced (unresectable Stage III or Stage IV) disease; d) No previous systemic corticosteroid therapy within 7 days; steroids for symptoms related to brain disease, developed during treatment are allowed; e) Prior adjuvant treatment with IFN or other immunotherapy allowed with exception of anti-CTLA-4; f) Presence of asymptomatic brain metastases: patients must have measurable metastases in the brain, defined as lesions that can be accurately measured in 2 dimensions as = 0.5 cm (maximum 2 cm) in the brain MRI with contrast; g) Pts who have been previously treated with brain stereotactic radiotherapy (SRT), whole-brain radiotherapy (WBRT) and/or surgery, must have developed new measurable brain lesions; h) Have a full set of baseline (i.e., Screening) digital images of cutaneous lesions and radiographic images, including, but not limited to: MRI of brain, CT of chest, abdomen, pelvis and soft tissue. All images must be of adequate quality as detailed in Section 6.4.1 of the protocol; i) Life expectancy 12 weeks; j) ECOG performance status of 0 or 1; k) Required values for initial laboratory tests: i) WBC >=3500/uL ii) ANC >=2000/uL iii) Platelets >=100 x 103/uL iv) Hemoglobin >=9 g/dL v) Creatinine =12 consecutive months without another cause or (2) For women with irregular menstrual periods and on hormone replacement therapy (HRT), a documented serum follicle stimulating hormone (FSH) level > 35 mIU/mL Are the trial subjects under 18? no Number of subjects for this age range: 0 F.1.2 Adults (18-64 years) yes F.1.2.1 Number of subjects for this age range 160 F.1.3 Elderly (>=65 years) no F.1.3.1 Number of subjects for this age range
Exclusion criteria
Exclusion criteria: 1) Sex and Reproductive Status a) WOCBP who are unwilling or unable to use an acceptable method to avoid pregnancy for the entire study period and for up to 8 weeks after the study; b) Women who are pregnant or breastfeeding; c) Women with a positive pregnancy test on enrollment or prior to investigational product administration; d) Sexually active fertile men not using effective birth control if their partners are WOCBP. 2) Target Disease Exceptions a) Any 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, carcinoma in situ of the cervix; b) Primary ocular or mucosal melanoma. 3) Medical History and Concurrent Diseases a) Symptomatic brain metastases requiring immediate local intervention (radiotherapy (RT) and/or surgery); b) Leptominingeal involvement by disease; c) Autoimmune disease: Patients with a documented history of Inflammatory Bowel Disease, including ulcerative colitis and Crohn’s disease are excluded from this study as are patients with a documented history of symptomatic autoimmune disease (eg, rheumatoid arthritis, systemic progressive sclerosis [scleroderma], Systemic Lupus Erythematosus, autoimmune vasculitis [eg, Wegener’s Granulomatosis] and autoimmune hepatitis. Subjects with motor neuropathy considered of autoimmune origin (eg, Guillain-Barre Syndrom) are also excluded from this study; d) Any underlying medical condition, which in the opinion of the investigator, will make the administration of study drug hazardous or obscure the interpretation of adverse events, such as a condition associated with frequent diarrhea. 4) Prohibited Treatments and/or Therapies a) Concomitant therapy with any anti-cancer agent; immunosuppressive agents; any non-oncology vaccine therapy used for prevention of infectious diseases (for up to 1 month prior to or after any dose of study drug); surgery or radiotherapy (except as described in Sections 5.5.1 and 5.5.2); other investigational anti-cancer therapies; or chronic use of systemic corticosteroids (used in the management of cancer or non-cancer-related illnesses); b) Previous treatment with other investigational products, including cancer immunotherapy, within 30 days; c) Prior treatment with anti-CTLA-4 and/or fotemustine. 5) Other Exclusion Criteria a) Prisoners or subjects who are involuntarily incarcerated; b) Subjects who are compulsorily detained for treatment of either a psychiatric or physical (eg, infectious disease) illness.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Main Objective: To compare the efficacy of the combination of ipilimumab and fotemustine versus fotemustine in terms of overall survival (OS) in patients with metastatic melanoma with brain metastasis;Secondary Objective: To assess safety, tolerability and feasibility of the combination. To further describe efficacy using the following tumor response indicators and clinical endpoints (with modified WHO – mWHO - tumor response criteria and with immune-related response criteria - irRC): a) Disease Control rate (DCR) in and outside the brain; b) Progression-Free Survival (PFS); three- and 6-months brain PFS rates; c) Objective Response Rate, Duration of response, Time to response; To evaluate HRQoL To assess the pharmacodynamic effects of ipilimumab and fotemustine in combination on Absolute Lymphocyte Count (ALC). To assess associations between ALC and anti-tumor activity of ipilimumab and fotemustine in combination. Translational studies a) To investigate changes in melanoma-specific humoral immune responses;Primary end point(s): The primary endpoint in this study will be overall survival (OS) of fotemustine versus the combination of ipilimumab and fotemustine in patients with metastatic melanoma with brain metastasis.;Timepoint(s) of evaluation of this end point: Tumor assessment with radiographic imaging (e.g. MRI of brain, CT of chest, abdomen, pelvis, other soft tissues) and digital photographs of skin lesions will be performed for all subjects at Screening, week 12, then every 8 weeks at weeks 20, 28, 36 and every 12 weeks from week 36 onwards, for all non-progressing subjects. At each evaluation investigators will assess the overall response (complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) (as categorized by mWHO and irRC). | — |
Secondary
| Measure | Time frame |
|---|---|
| Secondary end point(s): Secondary endpoints include: To assess safety, tolerability and feasibility of the combination: all subjects who receive at least 1 dose of study treatment will be evaluated for safety parameters To further describe efficacy using the following tumor response indicators and clinical endpoints (with modified WHO – mWHO - tumor response criteria and with immune-related response criteria - irRC): a) Disease Control Rate (DCR) in and outside the brain; b) Progression-free Survival; three- and 6-months brain progression-free survival rates; c) Objective Response Rate, Duration of response, Time to response; To evaluate HRQoL Sopravvivenza libera da progressione, e velocità di progressione delle metastasi al cervello a tre e 6 mesi. Tasso di risposta obiettiva, durata della risposta, tempo di risposta Valutazione HRQoL;Timepoint(s) of evaluation of this end point: Tumor assessment with radiographic imaging (e.g. MRI of brain, CT of chest, abdomen, pelvis, other soft tissues) and digital photographs of skin lesions will be performed for all subjects at Screening, week 12, then every 8 weeks at weeks 20, 28, 36 and every 12 weeks from week 36 onwards, for all non-progressing subjects. At each evaluation investigators will assess the overall response (complete response (CR), partial response (PR), stable disease (SD) or Progressive Disease (PD) (as categorized by mWHO and irRC). | — |
Countries
Italy
Contacts
Public ContactMedical Oncology and Immunotherapy
Azienda Ospedaliera Universitaria Senese
Outcome results
None listed