A Phase II Study of Intratumoral Application of L19IL2 in Patients With Stage III/IV Melanoma.
Overview
- Phase
- Phase 2
- Intervention
- Intratumoral injections of L19IL2
- Conditions
- Malignant Melanoma
- Sponsor
- Philogen S.p.A.
- Enrollment
- 25
- Locations
- 3
- Primary Endpoint
- Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12 .
- Status
- Completed
- Last Updated
- 11 years ago
Overview
Brief Summary
Phase II, non-randomized, multicenter, prospective study designed to test the efficacy and safety of intratumorally administered L19IL2 in patients suffering from metastatic melanoma.
Detailed Description
Phase II, non-randomized, multicenter, prospective study designed to test the efficacy and safety of intratumorally administered L19IL2. L19IL2 binds with high affinity to the EDB domain of Fibronectin, a marker of angiogenesis which is strongly upregulated in malignant melanoma lesions. This binding leads to an increased residence time of the protein at the site of disease. The biologic effect of the IL2 moiety is identical to the one of free IL-2. The study treatment is up to 20 MioIU L19IL2 per week in patients suffering from histopathologically-proven malignant melanoma with presence of injectable soft-tissue metastases either in clinical stage III or stage IV M1a without visceral metastases. The duration of treatment could be up to 20 weeks. After the end of study visit follow-up is performed every 6 weeks until 12 months from enrollment of each patient. Tumor assessment will be performed within 2 weeks before start of treatment and at week 12 using immune-related response criteria and RECIST 1.1. To assure that patients do not develop visceral metastases under treatment, an additional tumor assessment will be performed already at week 6 after start of therapy. Assessments at week 24 and 36 will be performed according to RECIST vs. 1.1 criteria only. Treatment emergent adverse events will be summarized by Common Toxicity Criteria (version 4.02, CTCAE) and worst grade for all treated patients. Laboratory values and change in vital signs will be summarized.
Investigators
Eligibility Criteria
Inclusion Criteria
- •Histopathologically proven malignant melanoma.
- •Presence of measurable and injectable soft tissue metastases either in clinical stage III or stage IV M1a.
- •Males or females, age \>/= 18 years.
- •Either without, or after one line of prior systemic treatment for metastatic disease.
- •ECOG performance status \<
- •LDH \< 2 x the upper limit of normal.
- •Life expectancy of at least 12 weeks.
- •Absolute neutrophil count \> 1.5 x 10\^9/L.
- •Hemoglobin \> 9.0 g/dL.
- •Platelets \> 100 x 10\^9/L.
Exclusion Criteria
- •Primary ocular melanoma.
- •Presence of visceral metastases at screening.
- •Evidence of active brain metastases at screening.
- •Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, Tis \& Ti) or any cancer curatively treated \< 5 years prior to study entry.
- •History of HIV infection or infectious hepatitis B or C.
- •Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study.
- •History within the last year of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris.
- •Inadequately controlled cardiac arrhythmias including atrial fibrillation.
- •Heart insufficiency (\> Grade II, New York Heart Association (NYHA) criteria).
- •Uncontrolled hypertension.
Arms & Interventions
L19IL2
Intervention: Intratumoral injections of L19IL2
Outcomes
Primary Outcomes
Rate of patients with complete response (CR) of L19IL2 treated Index/Non-Index lesions at week 12 .
Time Frame: week 12
Secondary Outcomes
- Safety of intratumoral administration of L19IL2(1-29 days)
- Rate of patients with complete response (CR), partial response (PR) and stable disease (SD) of L19IL2 treated Index/Non-Index lesions at week 12.(week 12)
- Duration of objective response and disease control of L19IL2 treated Index/Non-Index lesions(week 6-46)
- Overall survival (OS)(1 year)
- Rate of patients with complete response (CR), partial response (PR) and stable disease (SD)of all metastases(week 12)
- Objective response rate of all metastases(week 24, week 36)
- Disease control rate of all metastases(week 24, week 36)