Clinical Study Phase II of L19IL2 in Combination With Dacarbazine in Patients With Metastatic Melanoma

• Register: ClinicalTrials.gov
• Last refreshed on: 19 February 2015
• Main ID: NCT01055522
• Date of registration: 22/01/2010
• Prospective Registration: No
• Primary sponsor: Philogen S.p.A.
• Public title: Clinical Study Phase II of L19IL2 in Combination With Dacarbazine in Patients With Metastatic Melanoma
• Scientific title: 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
• Date of first enrolment: June 2008
• Target sample size: 102
• Recruitment status: Terminated
• URL: http://clinicaltrials.gov/show/NCT01055522
• Study type: Interventional
• Study design: Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment
• Phase: Phase 2

Countries of recruitment

Austria, Germany, Italy, Switzerland

Contacts

• Name: Claus Garbe, Prof. M.D.
• Affiliation: University Hospital Tuebingen (Germany)

• Name: Chiara Matilde Catania, Dr
• Affiliation: European Istitute of Oncology Milan (Italy)

Key inclusion & exclusion criteria

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
109/L

- 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
screening

Exclusion criteria:

- Primary ocular melanoma

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

- 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.



Age minimum: 18 Years
Age maximum: N/A
Gender: Both

Health Condition(s) or Problem(s) studied

Metastatic Melanoma

Intervention(s)

Drug: Arm 1: L19IL2 + Dacarbazine

Drug: ARM 2: L19IL2 + Dacarbazine

Drug: Arm 3: Dacarbazine

Primary Outcome(s)

To evaluate Objective response rate (ORR) by CT or MRI [Time Frame: 18 weeks]

To establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of Dacarbazine [Time Frame: 21 days]

Secondary Outcome(s)

To estimate progression -free survival (PFS) [Time Frame: 1 year]

To assess safety and tolerability [Time Frame: 1 year]

To estimate overall survival (OS) [Time Frame: 1 year]

To investigate the Pharmacokinetics of L19IL2, dacarbazine and 5-aminoimidazole -4 carboxamide (AIC). [Time Frame: 42 days]

To investigate Antitumor activity of L19IL2 with dacarbazine in patients with metastatic melanoma by TC or MRI [Time Frame: 18 weeks]

Evaluation of the immunological activity of study treatment [Time Frame: 1 year]

To investigate the induction of human anti-fusion protein antibodies (HAFA) [Time Frame: 1 year]

Secondary ID(s)

2007-005737-11

PH-L19IL2DTIC-03/07

Source(s) of Monetary Support

Please refer to primary and secondary sponsors

Secondary Sponsor(s)

Eudax S.r.l.