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Metastatic Melanoma Stage IVPhase 1/2NCT02076646

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

A Phase 1/2 study testing L19IL2 - Ph I, L19IL2 at RD - Ph II and DTIC in people with Metastatic Melanoma Stage IV, run by Philogen S.p.A. at 2 sites in 2 countries.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

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

Who is it for?
Ages 18 to 70 years
Conditions the study is for
Metastatic Melanoma Stage IV
What is being tested?
L19IL2 - Ph I, L19IL2 at RD - Ph II and DTIC
Type of treatment
Injection or infusion
Could I receive a placebo?
No, everyone receives an active treatment
How many people
96 participants
Where
2 sitesin 2 countries
Study dates
31 Jul 2013to Jun 2022
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 70 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • 18-70 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.
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  • 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.

Who cannot join

  • 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
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  • 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
  • History of acute or subacute coronary syndromes including myocardial infarction, unstable or severe stable angina pectoris
  • Heart insufficiency > grade II NYHA criteria
  • Uncontrolled hypertension
  • Ischemic peripheral vascular disease
  • Active infection or incomplete wound healing.
  • History or evidence of active autoimmune disease.
  • Known history of allergy to intravenously administered proteins/peptides/antibodies
  • History of organ allograft.or allogeneic peripheral blood progenitor cell or bone marrow transplantation
  • Major trauma including surgery within 4 weeks prior to entering the study.
  • Any underlying medical or psychiatric condition which in the opinion of the investigator will make administration of study drug hazardous or hinder the interpretation of study results (e.g. AE).
  • Melanoma patients with BRAF 600 E mutation who are amenable to receive approved treatments able to extend overall survival.

Trial locations and contacts

2 sites in 2 countries.

2 sites in 2 countries

Germany1 site

  • University Hospital

    Tübingen

Other trials in Germany

Italy1 site

  • Azienda Ospedaliera Universitaria Senese

    Siena

Other trials in Italy

About this study

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

Read the detailed description

A prospective, open-label, multi-center, Phase I/II dose escalation study in which cohorts of 3-6 patients with metastatic melanoma will be assigned to receive escalating doses of L19-IL2 in combination with a fixed dose of Dacarbazine.

After definition of MTD and RD 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 to receive open label the combination treatment at the RD (Arm 1) or DTIC monotherapy (Arm 2).

Being tested
L19IL2 - Ph I, L19IL2 at RD - Ph II, DTIC
Keywords
Interleukin, IL2, monoclonal, antibody, cytokine, Dacarbazine, metastatic, melanoma, tumor targeting, Dose definition, L19
Medical subject headings
Melanoma, Neoplasm Metastasis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • L19IL2 - Ph IDrug

    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).

  • L19IL2 at RD - Ph IIDrug

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

  • DTICDrug

    Also called DETICENE®

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

Study groups in NCT02076646
Study groupRoleWhat they receive
Ph I: L19IL2 + DTICExperimentalCohorts 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.
Receives: Drug: L19IL2 - Ph I; Drug: DTIC
Ph II - ARM 1: L19IL2 at RD + DTICExperimentalDuring 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.
Receives: Drug: L19IL2 at RD - Ph II; Drug: DTIC
Ph II - ARM 2: DTIC monotherapyActive comparatorDuring 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.
Receives: Drug: DTIC

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. 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

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

  2. Phase II: best objective response rate (BORR)

    Evaluation of antitumor activity

    Measured: Up to 1 year

Secondary outcomes (10)

  1. Phase I: best objective response rate (BORR)

    Evaluation of antitumor activity

    Measured: Up to 1 year

  2. Phase I: duration of objective response

    Evaluation of the antitumor activity

    Measured: From week 6 up to 1 year

  3. Phase I: disease control rate

    Evaluation of the antitumor activity

    Measured: At 6 months

  4. Phase I: median progression free survival (mPFS)

    Evaluation of the antitumor activity

    Measured: Up to 1 year

  5. Phase I: median overall survival and overall survival rate

    Evaluation of the antitumor activity

    Measured: Up to 1 year

  6. Phase II: safety and tolerability of L19-IL2 in combination with DTIC vs DTIC alone.

    Safety evaluation including AEs, SAE and standard laboratory assessment

    Measured: Up to 1 year

  7. Phase II: duration of objective response

    Measured: Up to 1 year

  8. Phase II: disease control rate

    Measured: At 6 months

  9. Phase II: median progression free survival (mPFS)

    Measured: Up to 1 year

  10. Phase II: median overall survival and overall survival rate

    Measured: Up to 1 year

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted3 Mar 2014 (estimated)
  2. Study start31 Jul 2013
  3. Primary completion17 May 2016
  4. Study completionJun 2022 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
None (open label)
Enrolment
96 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02076646
Sponsor's protocol ID
PH-L19IL2DTIC-04-12
Status last verified
Apr 2022
First submitted
24 Feb 2014
Last updated
14 Apr 2022
Results posted
No
Data monitoring committee
No

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing L19IL2 - Ph I, L19IL2 at RD - Ph II and DTIC in people with Metastatic Melanoma Stage IV, run by Philogen S.p.A. at 2 sites in 2 countries.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 15 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in Germany, Italy. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Phase I: maximum tolerated dose (MTD) and recommended dose (RD) of L19IL2 (time frame: From day 1 to day 21 of Cycle 1 (each cycle is 21-days)). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02076646.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Apr 2022.

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