F16IL2 Plus Paclitaxel in Metastatic Merkel Cell Carcinoma

NCT02054884 | Terminated Phase 2

• 1 other identifier: PH-F16IL2TAXO-03/12
• Study Type: interventional
• Target: 13
• Locations: 6 countries
• Sites: 8

Brief Summary

There is no standard treatment for Merkel cell carcinoma(MCC), as no randomized trials have been conducted to establish standard of care. Despite a sizable number of objective responses induced by combination cyototoxic chemotherapy, a prolongation of patients overall survival has never been demonstrated. This open-label, randomized, double-arm, multi-centre, phase II study of F16IL2 in combination with paclitaxel versus paclitaxel monotherapy, proposes to test the therapeutic efficacy of F16IL2 plus paclitaxel in patients with metastatic Merkel cell carcinoma, who are not amenable to surgery. A total of 90 patients with Merkel cell carcinoma will be enrolled and treated during the study; 45 patients will receive the combination treatment of F16IL2 and paclitaxel (Arm A), and 45 patients will receive paclitaxel monotherapy (Arm B).

Conditions

Merkel Cell Carcinoma

Keywords

Interleukin, IL2, F16, monoclonal, antibody, cytokine Paclitaxel, Merkel cell carcinoma

Outcome Measures

Primary Outcomes (1)

• Efficacy of F16IL2 in combination with paclitaxel vs. paclitaxel monotherapy (RECIST v1.1, irRC)

  12 months

Secondary Outcomes (3)

• Overall survival rate

  12 months

• Treatment efficacy (ORR, DCR)

  36 months

• Safety and tolerability of the combination treatment with F16IL2 and paclitaxel

  36 months

Study Arms (2)

Arm A: F16IL2 in combination with paclitaxel

EXPERIMENTAL

Drug: Arm A: F16IL2 in combination with paclitaxel

Arm B: Paclitaxel

EXPERIMENTAL

Drug: Arm B: Paclitaxel

Interventions

Arm A: F16IL2 in combination with paclitaxel DRUG

Intravenous (i.v.) 1 hour infusions of paclitaxel 90 mg/m\^2 followed, after 30 min pause, by 3 hour i.v. infusions of F16IL2 35 Mio IU on days 1, 8, 15 of each 28 day cycle. Patients will receive 4 week cycles of study therapy for a maximum of 24 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent.

Arm A: F16IL2 in combination with paclitaxel

Arm B: Paclitaxel DRUG

Intravenous (i.v.) 1 hour infusions of Paclitaxel 90 mg/m\^2 on days 1, 8, 15 of each 28 day cycle. Patients will receive 4 week cycles of study therapy for a maximum of 24 weeks, or until disease progression, unacceptable toxicity or withdrawal of consent.

Arm B: Paclitaxel

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with advanced or metastatic Merkel cell carcinoma (MCC) not amenable to surgery and who have not received previous systemic therapy with taxanes; diagnosis of MCC must be histologically confirmed (evaluation of primary lesions or advanced disease) and endorsed by the IMMOMEC central dermatopathology center (central review of diagnosis at the Department of General Dermatology, Medical University of Graz). Patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator
• Patients aged ≥ 18 ≤ 75 years
• ECOG performance status ≤ 1
• Patients must have measurable disease including cutaneous and subcutaneous metastases as defined by RECIST v.1.1 criteria or immune related response Criteria (irRC) as assessed by CT or MRI and/or ultrasound within 4 weeks before the first study drug administration.
• All acute side effects from any prior therapy must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v4.03) Grade ≤ 1;.
• Adequate hematologic, liver and renal function:
• Absolute neutrophil count (ANC) ≥ 1.5 x 109/L, platelets ≥ 100 x 109/L, haemoglobin (Hb) ≥ 9.0 g/dl
• Alkaline phosphatase (AP), alanine aminotransferase (ALT) and/or aspartate aminotransferase ≤ 3 x upper limit of reference range (ULN), and total bilirubin ≤ 2.0 mg/gL unless liver involvement by the tumor, in which case the transaminase levels could be ≤ 5 x ULN
• Creatinine ≤ 1.5 UL or 24 h creatinine clearance ≥ 50 mL/min
• Negative serum pregnancy test for females of childbearing potential within 14 days of starting treatment
• If of childbearing potential, agreement to use adequate contraceptive methods (e.g., oral contraceptives, condoms, or other adequate barrier controls, intrauterine contraceptive devices, or sterilization) beginning at the screening visit and continuing until 3 months following last treatment with study drug
• Evidence of a personally signed and dated EC-approved Informed Consent form indicating that the patient (or legally acceptable representative) has been informed of all pertinent aspects of the study
• Willingness and ability to comply with the scheduled visits, treatment plan, laboratory tests and other study procedures

You may not qualify if:

• Life expectancy of less than 3 months
• Any previous taxanes therapy
• Previous or concurrent CLL patients
• Any other malignancy from which the patient has been disease-free for less than 2 years prior to study entry, with the exception of adequately treated and cured cervical carcinoma in situ, basal or squamous cell carcinoma, superficial bladder cancer, or in situ melanoma
• Presence of uncontrolled infections or other severe concurrent disease, which, in the opinion of the investigator, would place the patient at undue risk or interfere with the study
• Presence of known brain metastases
• Chronic-active hepatitis B, C, or HIV
• Severe cardiovascular disease:
• History 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)
• Irreversible cardiac arrhythmias requiring permanent medication
• LVEF \< 50% and/or abnormalities observed during baseline 2D-ECHO or 12-lead ECG investigations
• Uncontrolled hypertension
• Ischemic peripheral vascular disease (Grade IIb-IV)
• Severe rheumatoid arthritis; or other uncontrolled autoimmune disease

Sponsors & Collaborators

• Philogen S.p.A.: lead
• Immatics Biotechnologies GmbH: collaborator

Study Sites (8)

Medical University Hospital

Graz, Austria

Location

Herlev- University Hospital

Herlev, Denmark

Location

Saint-Louis- Hospital

Paris, France

Location

Charité- Medical University Hospital

Berlin, Germany

Location

Universitätsklinik Essen

Essen, Germany

Location

Eberhard-Karls- University Hospital

Tübingen, Germany

Location

ICMiD- University Hospital

Barcelona, Spain

Location

Nottingham Trent- University Hospital

Nottingham, United Kingdom

Location

MeSH Terms

Conditions

Carcinoma, Merkel Cell

Interventions

Paclitaxel

Condition Hierarchy (Ancestors)

Polyomavirus Infections; DNA Virus Infections; Virus Diseases; Infections; Tumor Virus Infections; Carcinoma, Neuroendocrine; Neuroendocrine Tumors; Neuroectodermal Tumors; Neoplasms, Germ Cell and Embryonal; Neoplasms by Histologic Type; Neoplasms; Adenocarcinoma; Carcinoma; Neoplasms, Glandular and Epithelial; Neoplasms, Nerve Tissue

Intervention Hierarchy (Ancestors)

Taxoids; Cyclodecanes; Cycloparaffins; Hydrocarbons, Alicyclic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Diterpenes; Terpenes

Study Officials

• Jürgen C. Becker, Prof.

  Medical University of Graz, Austria

  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 31, 2014
• First Posted: February 4, 2014
• Study Start: October 25, 2013
• Primary Completion: December 31, 2016
• Study Completion: December 15, 2017
• Last Updated: May 18, 2018

Record last verified: 2018-05

Locations

GB (1); DK (1); DE (3); AU (1); FR (1); ES (1)