A Phase I/II Dose Escalation Study of the Tumor-targeting Human L19-IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Dacarbazine for Patients With Metastatic Melanoma

NCT02076646 | Unknown Phase 1

• 1 other identifier: PH-L19IL2DTIC-04-12
• Study Type: interventional
• Target: 96
• Locations: 2 countries
• Sites: 2

Brief Summary

A prospective, open-label, multi-center, Phase I/II study of L19IL2 in combination with Dacarbazine in patients with metastatic melanoma.

Conditions

Metastatic Melanoma Stage IV

Keywords

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

Outcome Measures

Primary Outcomes (2)

• Phase I: maximum tolerated dose (MTD) and recommended dose (RD) of L19IL2

  Establish the MTD and the RD of L19IL2 (in combination with dacarbazine) to be used for phase II study

  From day 1 to day 21 of Cycle 1 (each cycle is 21-days)

• Phase II: best objective response rate (BORR)

  Evaluation of antitumor activity

  Up to 1 year

Secondary Outcomes (10)

• Phase I: best objective response rate (BORR)

  Up to 1 year

• Phase I: duration of objective response

  From week 6 up to 1 year

• Phase I: disease control rate

  At 6 months

• Phase I: median progression free survival (mPFS)

  Up to 1 year

• Phase I: median overall survival and overall survival rate

  Up to 1 year

Study Arms (3)

Ph I: L19IL2 + DTIC

EXPERIMENTAL

Cohorts of 3-6 patients will receive escalating doses of L19-IL2 until MTD is reached. L19-IL2 will be administered on days 1, 8 \& 15 of each 21-day-cycle. Dacarbazine will be given at a fixed dose on day 1 of each 21-day cycle, 30 minutes after the end of the L19-IL2 infusion.

Drug: L19IL2 - Ph I; Drug: DTIC

Ph II - ARM 1: L19IL2 at RD + DTIC

EXPERIMENTAL

During the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio: 30 patients assigned to Arm 1 will receive L19IL2 at the RD + DTIC at a fixed dose.

Drug: L19IL2 at RD - Ph II; Drug: DTIC

Ph II - ARM 2: DTIC monotherapy

ACTIVE COMPARATOR

During the phase II part of this study, 60 patients with Stage IV M1a and M1b melanoma will be randomized in a 1:1 ratio: 30 patients assigned to Arm 2 will receive DTIC at a fixed dose as monotherapy.

Drug: DTIC

Interventions

L19IL2 - Ph I DRUG

During phase I part of the study, increasing dose of L19IL2 from one cohort to the next will be performed in steps of 160,000 IU/kg starting at 480,000 IU/kg (i.e., 0.48; 0.64; 0.80 MioIU/kg until MTD is reached).

Ph I: L19IL2 + DTIC

L19IL2 at RD - Ph II DRUG

L19IL2 at RD will be administered to Arm 1 patients during phase II part of the study.

Ph II - ARM 1: L19IL2 at RD + DTIC

DTIC DRUG

Dacarbazine: 1 hour intravenous infusion on day 1 of each 21-cycle at a dosage of 1000 mg/m2 (fixed dose).

Also known as: DETICENE®

Ph I: L19IL2 + DTIC; Ph II - ARM 1: L19IL2 at RD + DTIC; Ph II - ARM 2: DTIC monotherapy

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• years of age, inclusive
• Must have histologically or cytologically confirmed cutaneous metastatic melanoma (Stage IV). For the Phase II part only patients with Stage IV M1a or M1b will be enrolled.
• Must have measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST 1.1) as identified by CT or MRI scan within 28 days before the first study drug administration.
• Baseline LDH within normal range
• Maximal 1 line of previous systemic treatment for metastatic disease (prior adjuvant melanoma therapy, e.g., IFN, is permitted.
• For women of childbearing potential, a negative pregnancy test within 72 hours prior to the first dose of study treatment.
• Women with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 12 weeks after the last dose of study medication.
• Men with reproductive potential must be willing to practice acceptable methods of birth control during the study and for up to 12 weeks after the last dose of study medication.
• Must have Eastern Cooperative Oncology Group (ECOG) Performance Status of 0-1
• Life expectancy of at least three months
• Adequate organ function: serum creatinine ≤ 1.5 x ULN, total bilirubin ≤ 30 mM/L (or mg/dL, ≤ 2.0 mg/dL), hepatic transaminases ≤ 2.5 x ULN, alkaline phosphatase ≤ 2.5 x ULN.
• ANC count ≥ 1.5 x 10\^9/L, platelet count ≥ 100 x 10\^9/L, hemoglobin \> 9 g/dL
• Normal 12-lead ECG and normal bidimensional echocardiogram or MUGA
• All toxic effects of prior therapy must have resolved to grade ≤1 unless otherwise specified above
• Willing and able to give written informed consent.

You may not qualify if:

• Pregnant or breastfeeding female
• Primary ocular melanoma
• Primary mucosal melanoma
• Use of any investigational or other anti-cancer drug within 28 days or 5 half-lives, whichever is longer, preceding the first dose of DTIC and L19-IL2
• Prior radiation to a target lesion, unless there has been clear progression of the lesion since radiotherapy
• A history of known Human Immunodeficiency Virus (HIV), Hepatitis B Virus (HBV), or Hepatitis C Virus (HCV) infection
• History or clinical evidence of brain metastases or leptomeningeal disease
• Any other malignancy from which the patient has been disease-free for less than 5 years, with the exception of adequately treated and cured basal or squamous cell skin cancer, superficial bladder cancer, or carcinoma in situ of the cervix
• Treatment with DTIC within 6 months before start of study
• Treatment with Ipilimumab within 6 months before start of study
• Hypersensitivity to DTIC
• Concomitant use of drugs known to alter cardiac conduction
• Chronic use of corticosteroids used in the management of cancer or non-cancer-related illness
• Unstable or serious concurrent uncontrolled medical conditions
• Inadequately controlled cardiac arrhythmias including atrial fibrillation

Sponsors & Collaborators

• Philogen S.p.A.: lead

Study Sites (2)

University Hospital

Tübingen, Germany

Location

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

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

• Claus Garbe, Prof. M.D.

  University Hospital Tuebingen (Germany)

  PRINCIPAL INVESTIGATOR

• Michele Maio, Dr.med.

  Azienda Ospedaliera Universitaria Senese, Siena (Italy)

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: February 24, 2014
• First Posted: March 3, 2014
• Study Start: July 31, 2013
• Primary Completion: May 17, 2016
• Study Completion: June 1, 2022
• Last Updated: April 14, 2022

Record last verified: 2022-04

Locations

DE (1); IT (1)