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Dose Definition and Activity Evaluation Study of the Tumor-Targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Combination With Dacarbazine in Patients With Metastatic Melanoma

Phase 2
18 Years
Open (Enrolling)
Metastatic Melanoma

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Trial Information

Dose Definition and Activity Evaluation Study of the Tumor-Targeting Human L19IL2 Monoclonal Antibody-Cytokine Fusion Protein in Combination With Dacarbazine in Patients With Metastatic Melanoma

Dose limiting toxicity will be assessed during the dose-escalation part of Phase IIa from
day 1 through day 21 of the first cycle.

Response will be measured using RECIST criteria every 6 weeks (after every 2 cycles of
treatment). Patients with stable or responding disease at each assessment may receive
additional treatment for a maximum of 6 cycles of induction. Patients with stable or
responding disease after induction may receive L19IL2 (without dacarbazine) every 2 weeks as
maintenance therapy.

Tumor expression of ED-B FN and tumor uptake of L19IL2 and of Dacarbazine will be assessed
via immunohistochemistry and/or other methods deemed appropriate on tumor tissue biopsies.
Tumor biopsy will be performed on superficial accessible cutaneous and/or subcutaneous
lesions only. Tumor biopsy will be considered optional and will not preclude patient entry
on to study should the patient refuse.

Pharmacokinetics of L19IL2, Dacarbazine and AIC will be assessed from serial blood samples
using standard methods.

Overall response rate, PFS, survival rate at 6 and 12 months, and overall survival time for
all patients and separately for the patients in the Phase IIb part will be assessed using
standard methods.

Inclusion Criteria:

- Histologically or cytologically confirmed unresectable metastatic (stage IV)
non-uveal melanoma

- Age > 18 years

- Measurable disease defined as at least one lesion that can be accurately and serially
measured per the modified RECIST criteria. Cutaneous lesions measuring at least 1 cm
will be considered measurable.

- Prior therapy for metastatic melanoma:

- Phase IIa - Dose definition: prior therapy allowed, including prior
chemotherapy; previous treatment with DTIC: patients should be treated > 6
months prior to study entry

- Phase IIb -Activity Evaluation: no prior therapy except radiation. However, if
radiation has been administered to a lesion, there must be radiographic evidence
of progression of that lesion in order for that lesion to constitute measurable
disease or to be included in the measured target lesions

- Fewer than 3 organs involved or cutaneous and/or subcutaneous metastasis only, for
PhaseIIb patients

- ECOG performance status < 2

- Life expectancy of at least 12 weeks

- Absolute neutrophil count > 1.5 x 109/L, hemoglobin > 9.0 g/dL and platelets > 100 x

- Total bilirubin ≤ 30 µmol/L (or ≤ 2.0 mg/Dl)

- ALT and AST ≤ 2.5 x the upper limit of normal (5.0 x ULN for patients with hepatic
involvement with tumor

- LDH < 2.0 x ULN for Phase IIa patients and normal LDH for the Phase IIb ones.

- Serum creatinine < 1.5 x ULN

- All toxic effects of prior therapy must have resolved to ≤ Grade 1 unless otherwise
specified above

- Negative serum pregnancy test (for women of child-bearing potential only) at

Exclusion criteria:

- Primary ocular melanoma

- Evidence of brain metastases, negative CT scan within two months before study

- 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 chronic 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.

- Inadequately controlled cardiac arrhythmias including atrial fibrillation

- History within the last year of acute or subacute coronary syndromes including
myocardial infarction, unstable or severe stable angina pectoris.

- Heart insufficiency (> Grade II, New York Heart Association (NYHA) criteria).

- Uncontrolled hypertension.

- Ischemic peripheral vascular disease (Grade Iib-IV).

- Severe diabetic retinopathy.

- Active autoimmune disease

- History of organ allograft or stem cell transplantation.

- Recovery from major trauma including surgery within 4 weeks prior to administration
of study treatment.

- Known history of allergy to IL2, dacarbazine, or other intravenously administered
human proteins/peptides/antibodies.

- Breast feeding female.

- Anti-tumor therapy within 4 weeks of the administration of study treatment.

- Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6
weeks before administration of study treatment.

- Previous DTIC treatment in the last 6 months prior to study entry

- Growth factors or immunomodulatory agents within 7 days of the administration of
study treatment.

- Patient requires or is taking corticosteroids or other immunosuppressant drugs on a
long-term basis. Limited use of corticosteroids to treat or prevent acute
hypersensitivity reactions is not considered an exclusion criterion.

- Any conditions that in the opinion of the investigator could hamper compliance with
the study protocol.

Type of Study:


Study Design:

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Outcome Measure:

To establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of Dacarbazine

Outcome Time Frame:

21 days

Safety Issue:


Principal Investigator

Chiara Matilde Catania, Dr

Investigator Role:

Principal Investigator

Investigator Affiliation:

European Istitute of Oncology Milan (Italy)


Italy: Ethics Committee

Study ID:




Start Date:

June 2008

Completion Date:

July 2013

Related Keywords:

  • Metastatic Melanoma
  • Interleukin, IL2, monoclonal, antibody, cytokine, Dacarbazine, metastatic, melanoma, tumor targeting, Dose definition
  • , L19
  • Melanoma