Stage III Melanoma, Stage IV Melanoma
Conditions
Keywords
Melanoma
Brief summary
The purpose of this study is to assess the overall disease control rate of Ofatumumab wo/w Dacarbazine in subjects with American Joint Committee on Cancer (AJCC 2009) unresectable stage III or stage IV melanoma.
Detailed description
This is a prospective, multicenter, open-label, sequential, 2-cohort, phase 2 study to assess the overall disease control rate of Ofatumumab according to criteria of RECIST (Response Evaluation Criteria in Solid Tumors) v. 1.1. in subjects with unresectable stage III B (T1- 4a, N2b-c), stage III C or stage IV (American Joint Committee on Cancer 2009) disease. Cohort 1: 10 eligible patients will be treated with ofatumumab alone. If interim analysis shows that at least 1 confirmed overall response occurs, an additional 19 eligible patients will be treated, for a total of 29 patients. Cohort 2: If no confirmed overall response by ofatumumab alone-therapy is seen in the first 10 patients, cohort 2 will be opened. Initially, 13 eligible patients will be treated with a combination of Dacarbazine plus ofatumumab. If interim analysis gives at least 2 confirmed overall responses, additional 26 patients will be recruited.
Interventions
BIOLOGICALOfatumumab
Ofatumumab will be administered at a dose of 1000mg iv weekly for 8 weeks and q4w for another 16 weeks
BIOLOGICALOfatumumab plus Dacarbazine
Ofatumumab will be administered at a dose of 1000mg iv weekly for 8 weeks and q4w for another 16 weeks. Dacarbazine administered q4w at a dose of 1000mg/m2, 4 days before next administration of Ofatumumab for 24 weeks.
Sponsors
Medical University of Vienna
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Patients older than 18 years * Signed informed consent * Metastatic non-ocular melanoma - unresectable stage III B (T1- 4a, N2b-c), stage III C (AJCC 2009) or stage IV (AJCC 2009). * measurable disease with more than one metastatic lesion, according to RECIST v. 1.1 criteria, * One of these metastases must be resectable prior to anti-CD20 therapy. * ECOG (Eastern Cooperative Oncology Group) performance status of 0-2. * As soon as BRAF or other kinase inhibitors are standard of care, we will include only patients who cannot be considered for those therapies. E.g. patients with tumors not carrying the respective mutational profile, patients refusing this kind of therapy for any reason, patients being not eligible to those therapies due to contraindications or disease progression under such kind of therapy. * Life expectancy of 3 month or longer * Negative pregnancy test in female patients of childbearing potential and adequate contraception in female patients of childbearing age.
Exclusion criteria
* Patients with active brain metastasis (exception: brain metastases being stable with and without corticosteroids for 2 months after treatment by surgery or radiation therapy) and immunoglobulin-deficiency will be excluded. Subjects meeting any of the following criteria must not be enrolled in an ofatumumab study: * Subjects who have current active hepatic or biliary disease (with exception of patients with Gilbert's syndrome, asymptomatic gallstones, liver metastases or stable chronic liver disease per investigator assessment) * Treatment with any known non-marketed drug substance or experimental therapy within 5 terminal half lives or 4 weeks prior to enrollment, whichever is longer, or currently participating in any other interventional clinical study * Other past or current malignancy. Subjects who have been free of malignancy for at least 5 years, or have a history of completely resected non-melanoma skin cancer, or successfully treated in situ carcinoma are eligible. * Chronic or current infectious disease requiring systemic antibiotics, antifungal, or antiviral treatment such as, but not limited to, chronic renal infection, chronic chest infection with bronchiectasis, tuberculosis and active Hepatitis C. * History of significant cerebrovascular disease in the past 6 months or ongoing event with active symptoms or sequelae * HIV positive * Clinically significant cardiac disease including unstable angina, acute myocardial infarction within six months prior to enrollment, congestive heart failure (NYHA III-IV), and arrhythmia unless controlled by therapy, with the exception of extra systoles or minor conduction abnormalities. * Positive serology for Hepatitis B (HB) defined as a positive test for HBsAg. In addition, if negative for HBsAg but HBcAb positive (regardless of HBsAb status), a HB DNA test will be performed and if positive the subject will be excluded. * Positive serology for hepatitis C (HC) defined as a positive test for HCAb (HC antibodies), in which case reflexively perform a HC RIBA (recombinant immunoblot assay) on the same sample to confirm the result * Screening laboratory values: hemoglobin \< 8g/dL platelets \<70 x 109/L leukocytes \<1.5 x 109/L creatinine \>2.0 times ULN (upper limit of normal) total bilirubin \>1.5 times ULN liver transaminase ALT \>2.5 times ULN alkaline phosphatase \>2.5 times ULN * Pregnant or lactating women * Male subjects unable or unwilling to use adequate contraception methods from study start to one year after the last dose of protocol therapy
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Disease control according to RECIST v. 1.1 criteria | 24 weeks | Disease control according to RECIST v. 1.1 criteria until week 24 |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of progression-free survival (PFS) | approximately 2 years | Assessment of progression-free survival (PFS) defined as the time from first day of treatment to the first documentation of disease progression or death, whichever occurs first. |
| Evaluation of cell biological responses | From date of inclusion until the date of first documented progression or date of death from any cause, whichever came first, assessed up to 24 weeks | in patients' blood and tumor samples |
| Duration of disease control | approximately 2 years | — |
| Overall survival | approximately 2 years | — |
Countries
Austria
Outcome results
None listed