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Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response
Phase: Proof of Principle phase II study
Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response
Study Duration:
Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months
Number of Subjects:
Mini-max two-stage Simon design:
• Step 1: 7 patients enrolled
If tumor antigen-specific immune response is observed in at least 3 patients:
• Step 2: recruitment of an additional 12 patients
Full description
Title: Radiotherapy as an immunological booster in patients with metastatic melanoma or renal cell carcinoma treated with High-dose Interleukin-2: evaluation of biomarkers of immunologic and therapeutic response
Phase: Proof of Principle phase II study
Study Design: Single center, open-label trial to assess the immune response and potential biomarkers predictive of response
Study Duration:
Total duration: 36 months Enrollment: 20 months Treatment: 5 months per patient Follow-up every three months
Primary objectives:
Secondary end points:
Number of Subjects:
Mini-max two-stage Simon design:
• Step 1: 7 patients enrolled
If tumor antigen-specific immune response is observed in at least 3 patients:
• Step 2: recruitment of an additional 12 patients
Study Product, Dose, Route, Regimen and duration of administration:
Three daily doses boost radiotherapy (XRT) at 6-12 Gy to at least 1, and up to a maximum of 5, metastatic fields, will be administrated on days -4 -3 -2 or -3 -2 -1 before the first and the third cycle of IL-2. The first day of administration of IL-2 of each cycle is the day +1.
Treatment with IL-2 (dose 18 MIU/m2/day in 500cc by continuous IV infusion for 72 hours) will start on day +1 and will be administered every 3 weeks up to 4 cycles, than every 3-4 weeks for a further 2 cycles.
IL-2 will be withheld for refractory hypotension (hypotension where isotropic or vasoactive therapy is ineffective and that persists despite specific medical therapy set), anuria for > 24 hours, respiratory distress, confusion, sustained ventricular tachycardia, signs of myocardial ischemia or myocarditis, persistant metabolic acidosis, atrial fibrillation and documented systemic infection.
Patients will be evaluated every 8 weeks with computed tomography to determine the response, and every 3 months after completion of treatment until death (the time of disease progression and the initiation of alternative therapies will also be documented).
Statistical Methodology:
A minimax two-stage Simon design will be employed. A 40% immune response will preclude further study, whereas a 70% response rate will indicate that further study would be warranted. Using alfa and beta errors of 0.10, 7 patients will be enrolled during the first stage, and if an immune response is observed in at least 3 patients the study will go on, and an additional 12 patients will be treated. The treatments will be considered active if a tumor antigen-specific immune response is observed in 11 out of 19 patients treated. The analysis will be performed on an intention to treat population, i.e. all patients having received at least one cycle of therapy.
Enrollment
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Inclusion criteria
Patients must have histologically or cytologically confirmed non resectable stage III or IV advanced melanoma or Renal Cell Carcinoma (RCC).
Patients must have a minimum of two lesions and one of which must be measurable, (it can be accurately measured in at least one dimension (longest diameter to be recorded) as >20 mm with conventional techniques or as >10 mm with spiral CT scan).
At least one tumor lesion accessible for bioptic sampling.
Prior lines (maximum 4) of chemotherapy, immunotherapy or biological therapy (e.g. inhibitors of B-Raf or c-Kit, Ipilimumab, etc.) for advanced disease are allowed (patients must have finished prior treatments at least 4 weeks before the first IL2 dose);
Male or Female, aged >= 18 years.
Life expectancy of greater than 3 months.
ECOG performance status <=1
Patients must have normal organ and marrow function as defined below:
no contraindication for the use of vasopressor agents
Female participants of child bearing potential and male participants whose partner is of child bearing potential must be willing to ensure that they or their partner use effective contraception during the study and for 3 months thereafter
Participant is willing and able to give informed consent for participation in the study.
Exclusion criteria
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46 participants in 1 patient group
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Central trial contact
Oriana Nanni, PhD
Data sourced from clinicaltrials.gov
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