Trial document





This study has been imported from ClinicalTrials.gov without additional data checks.
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  DRKS00005898

Trial Description

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Title

Phase II Study of the Tumor-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Paclitaxel in Patients With Metastatic Merkel Cell Carcinoma

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Trial Acronym

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URL of the Trial

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Brief Summary in Lay Language

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).

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Brief Summary in Scientific Language

F16IL2 has been studied in two clinical pase I/II trials in patients with different advanced
cancer types. One of them (Nr. EudraCT: 2007-006457-42) tested the administration of
therapeutic doses of paclitaxel (up to 90 mg/m2 on a weekly basis) together with escalating
doses of F16IL2 (from 5 Mio IU of IL2 equivalents in a weekly administration schedule, until
definition of MTD). More than 40 patients were treated in this clinical trial. As of today,
the highest F16IL2 dose tested corresponds to 45 Mio IU, but the dose escalataion of the
F16IL2/paclitaxel combination study is still ongoing.

In general, treatment of patients with F16IL2 plus paclitaxel was very well tolerated not
exceeding the expected toxicity of chemotherapy alone. Multiple objective and durable tumor
responses were observed in the F16IL2/paclitaxel combination trial(particularly in patients
with non small cell lung cancer or melanoma who had previously failed several lines of
chemotherapy). In addition to several disease stabilizations of previously progressive
patients.

Paclitaxel promotes the assembly of microtubules from tubulin dimers and stabilizes
microtubules by preventing depolymerisation. This stability results in the inhibition of the
normal reorganization of the microtubule network that is essential for vital interphase and
mitotic cellular functions. In addition, paclitaxel reduces abnormal arrays or bundles of
microtubules throughout the cell cycle and multiple asters of microtubules during mitosis.

F16 is a human recombinant antibody fragment in the scFv (single chain Fragment variable)
format that is directed against tenascin C, an angiogenesis marker common to most solid
tumors independent of the tumor type. ScFv(F16) selectively localizes in tumor tissues in
animal models as demonstrated both histologically and during mechanistic studies involving
mice transfected with orthotopic human tumours.

IL2, the human cytokine interleukin-2, is a potent stimulator of the immune response. It has
a central role in the regulation of T cell responses and effects on other immune cells such
as natural killer cells, B cells, monocyte/macrophages and neutrophils (Smith, 1988). IL2
can induce tumor regression through its ability to stimulate a potent cell-mediated immune
response in vivo (Rosenberg, 2000).

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Organizational Data

  •   DRKS00005898
  •   2015/03/03
  •   2014/01/31
  •   no
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Secondary IDs

  •   NCT02054884  (ClinicalTrials.gov)
  •   PH-F16IL2TAXO-03/12  (Philogen S.p.A.)
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Health Condition or Problem studied

  •   Merkel Cell Carcinoma
  •   C44 -  Other malignant neoplasms of skin
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Interventions/Observational Groups

  •   Drug: Arm A: F16IL2 in combination with paclitaxel
  •   Drug: Arm B: Paclitaxel
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Characteristics

  •   Interventional
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  •   Randomized controlled trial
  •   Open (masking not used)
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  •   Treatment
  •   Parallel
  •   II
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Primary Outcome

- Efficacy of F16IL2 in combination with paclitaxel vs. paclitaxel monotherapy (RECIST v1.1, irRC); time frame: 12 months

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Secondary Outcome

- Overall survival rate; time frame: 12 months
- Treatment efficacy (ORR, DCR); time frame: 36 months
- Safety and tolerability of the combination treatment with F16IL2 and paclitaxel; time frame: 36 months; Evaluation of the type and the number of adverse events eventually present

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Countries of Recruitment

  •   Austria
  •   Denmark
  •   France
  •   Germany
  •   Spain
  •   United Kingdom
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Locations of Recruitment

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Recruitment

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  •   2013/10/31
  •   90
  •   Multicenter trial
  •   International
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Inclusion Criteria

  •   Both, male and female
  •   18   Years
  •   75   Years
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Additional Inclusion Criteria

- 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

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Exclusion Criteria

- 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

- Severe diabetic retinopathy

- History of allograft or stem cell transplantation

- Major trauma including major surgery (e.g. visceral surgery) within 4 weeks of
administration of study treatment

- Known history of allergy to IL-2, taxanes, cremophor or other intravenously
administered human proteins/peptides/antibodies

- Pregnancy or breast-feeding. Female patient must agree to use effective
contraception, or be surgically sterile or postmenopausal. The definition of
effective contraception will be based on the European guideline ICH M3 rev 2.

- Treatment with an investigational study drug within four weeks before beginning of
treatment with F16IL2

- Previous treatment with monoclonal antibodies for biological therapy in the four
weeks before administration of study treatment

- Any conditions that in the opinion of the investigator could hamper compliance with
the study protocol.

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Addresses

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    • Philogen S.p.A.
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    • immatics Biotechnologies GmbH
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    • Medical University of Graz (Austria)
    • Jürgen C. Becker, Prof. 
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    • Jürgen C. Becker, Prof. 
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    •   +43 316 385 12538
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Sources of Monetary or Material Support

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    • Bitte wenden Sie sich an den Sponsor / Please refer to primary sponsor
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Status

  •   Recruiting ongoing
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Trial Publications, Results and other Documents

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The parameters in ClinicalTrials.gov and DRKS are not identical. Therefore the data import from ClinicalTrials.gov required adjustments. For full details please see the DRKS FAQs .
  •   1
  •   2014/02/23
* This entry means the parameter is not applicable or has not been set.