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

NCT01055522 | Terminated Phase 2

• 2 other identifiers: PH-L19IL2DTIC-03/072007-005737-11
• Study Type: interventional
• Target: 102
• Locations: 4 countries
• Sites: 10

Brief Summary

This Phase II clinical study is an open-label, multicenter study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma. The study is divided in two parts: a phase IIa part, designed to establish the recommended dose (RD) of L19IL2 when administered in combination with a fixed dose of Dacarbazine, as well as to determine the preliminary tolerability profile; the second phase IIb part evaluates the objective response rate (ORR) including a randomized study with a fixed dose of Dacarbazine with or without L19IL2, dosed at the RD determined in phase IIa.

Conditions

Metastatic Melanoma

Keywords

Interleukin, IL2, monoclonal, antibody, cytokine, Dacarbazine, metastatic, melanoma, tumor targeting, Dose definition; , L19

Outcome Measures

Primary Outcomes (2)

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

  21 days

• To evaluate Objective response rate (ORR) by CT or MRI

  18 weeks

Secondary Outcomes (7)

• To investigate the Pharmacokinetics of L19IL2, dacarbazine and 5-aminoimidazole -4 carboxamide (AIC).

  42 days

• To investigate the induction of human anti-fusion protein antibodies (HAFA)

  1 year

• To investigate Antitumor activity of L19IL2 with dacarbazine in patients with metastatic melanoma by TC or MRI

  18 weeks

• Evaluation of the immunological activity of study treatment

  1 year

• To estimate progression -free survival (PFS)

  1 year

Study Arms (3)

ARM 1: L19IL2 + Dacarbazin

EXPERIMENTAL

Drug: Arm 1: L19IL2 + Dacarbazine

ARM 2: L19IL2 + Dacarbazin

EXPERIMENTAL

Drug: ARM 2: L19IL2 + Dacarbazine

ARM 3: Dacarbazin

ACTIVE COMPARATOR

DTIC every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or for a maximum of 8 cycles, whichever occurs first

Drug: Arm 3: Dacarbazine

Interventions

Arm 1: L19IL2 + Dacarbazine DRUG

RD of L19IL2 determined in phase IIa. Induction Phase A: Intravenous (IV) infusion of L19IL2 on days 1, 3 and 5 of each 21-day cycle over 60 minutes via automated device (perfusor), for four consecutive 21-day cycles. Induction Phase B: Intravenous (IV) infusion of L19IL2 on days 1, 8 and 15 of each 21-day cycle over 60 minutes via automated device (perfusor), for four consecutive 21-day cycles. Maintenance: Intravenous (IV) infusion of L19IL2 on days 1, 8 and 15 of each 21-day cycle over 60 minutes via automated device (perfusor), for a maximum of 1 year after start of treatment. DTIC 1,000mg/m2 every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or one year from initiation of therapy, whichever occurs first

ARM 1: L19IL2 + Dacarbazin

Arm 3: Dacarbazine DRUG

Dacarbazine Dosage: 1,000 mg/m2 DTIC every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or for a maximum of 8 cycles, whichever occurs first.

Also known as: DETICENE®

ARM 3: Dacarbazin

ARM 2: L19IL2 + Dacarbazine DRUG

RD of L19IL2 determined in phase IIa. Intravenous (IV) infusion of L19IL2 on days 1, 8 and 15 of each 21-day cycle over 60 minutes via automated device (perfusor), for for a maximum of 1 year after start of treatment. DTIC 1,000mg/m2 every three weeks until disease progression, unacceptable toxicity, withdrawal of consent, or one year from initiation of therapy, whichever occurs first

ARM 2: L19IL2 + Dacarbazin

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Philogen S.p.A.: lead
• Eudax S.r.l.: collaborator

Study Sites (10)

Universitätsklinik Graz

Graz, Austria

Location

Charité- Universitätsmedizin Berlin

Berlin, Germany

Location

Universitätsklinikum Schleswig-Holstein-Campus Kiel

Kiel, Germany

Location

University Hospital

Tübingen, 72076, Germany

Location

University Hospital Pisa

Pisa, Tuscany, 56126, Italy

Location

A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (AN) (Italy)

Ancona, Italy

Location

European Institute of Oncology

Milan, 20141, Italy

Location

Istituto Nazionale Per Lo Studio E La Cura Dei Tumori Fondazione Giovanni Pascale Di Napoli

Napoli, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

Universitäts Spital Zürich

Zurich, Switzerland

Location

Related Publications (1)

• Eigentler TK, Weide B, de Braud F, Spitaleri G, Romanini A, Pflugfelder A, Gonzalez-Iglesias R, Tasciotti A, Giovannoni L, Schwager K, Lovato V, Kaspar M, Trachsel E, Menssen HD, Neri D, Garbe C. A dose-escalation and signal-generating study of the immunocytokine L19-IL2 in combination with dacarbazine for the therapy of patients with metastatic melanoma. Clin Cancer Res. 2011 Dec 15;17(24):7732-42. doi: 10.1158/1078-0432.CCR-11-1203. Epub 2011 Oct 25.

  PMID: 22028492 DERIVED

MeSH Terms

Conditions

Melanoma; Neoplasm Metastasis

Interventions

Dacarbazine

Condition Hierarchy (Ancestors)

Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Neoplasms, Nerve Tissue; Nevi and Melanomas; Skin Neoplasms; Neoplasms by Site; Skin Diseases; Skin and Connective Tissue Diseases; Neoplastic Processes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Triazenes; Organic Chemicals; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Chiara Matilde Catania, Dr

  European Istitute of Oncology Milan (Italy)

  PRINCIPAL INVESTIGATOR

• Claus Garbe, Prof. M.D.

  University Hospital Tuebingen (Germany)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 22, 2010
• First Posted: January 25, 2010
• Study Start: June 1, 2008
• Primary Completion: February 1, 2013
• Study Completion: February 1, 2014
• Last Updated: February 25, 2014

Record last verified: 2012-10

Locations

AU (1); CH (1); IT (5); DE (3)