Merkel Cell CarcinomaPhase 2NCT02054884
F16IL2 Plus Paclitaxel in Metastatic Merkel Cell Carcinoma
A Phase 2 study testing Arm A: F16IL2 in combination with paclitaxel and Arm B: Paclitaxel in people with Merkel Cell Carcinoma, run by Philogen S.p.A. at 8 sites in 6 countries.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Merkel Cell Carcinoma
- What is being tested?
- Arm A: F16IL2 in combination with paclitaxel and Arm B: Paclitaxel
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 13 participants
- Where
- 8 sitesin 6 countries
- Study dates
- 25 Oct 2013to 15 Dec 2017
- Phase
- Phase 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 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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:
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- 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
Who cannot join
- 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
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- 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.
Trial locations and contacts
8 sites in 6 countries.
8 sites in 6 countries
Germany3 sites
Charité- Medical University Hospital
Berlin
Universitätsklinik Essen
Essen
Eberhard-Karls- University Hospital
Tübingen
About this study
Official 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
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).
Read the detailed description
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).
- Conditions
- Merkel Cell Carcinoma
- Being tested
- Arm A: F16IL2 in combination with paclitaxel, Arm B: Paclitaxel
- Keywords
- Interleukin, IL2, F16, monoclonal, antibody, cytokine Paclitaxel, Merkel cell carcinoma
- Medical subject headings
- Carcinoma, Merkel Cell
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Arm A: F16IL2 in combination with paclitaxelDrug
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 B: PaclitaxelDrug
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.
| Study group | Role | What they receive |
|---|---|---|
| Arm A: F16IL2 in combination with paclitaxel | Experimental | Not described Receives: Drug: Arm A: F16IL2 in combination with paclitaxel |
| Arm B: Paclitaxel | Experimental | Not described Receives: Drug: Arm B: Paclitaxel |
What is being measured
The primary outcome is the main question the study is designed to answer.
Efficacy of F16IL2 in combination with paclitaxel vs. paclitaxel monotherapy (RECIST v1.1, irRC)
Measured: 12 months
Secondary outcomes (3)
Overall survival rate
Measured: 12 months
Treatment efficacy (ORR, DCR)
Measured: 36 months
Safety and tolerability of the combination treatment with F16IL2 and paclitaxel
Evaluation of the type and the number of adverse events eventually present
Measured: 36 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted4 Feb 2014 (estimated)
- Study start25 Oct 2013
- Primary completion31 Dec 2016
- Study completion15 Dec 2017
Why it stopped: Lack of enrollment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Merkel Cell CarcinomaStudies of the same condition, open and under way.
- More trials run by Philogen S.p.A.The sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 13 participants (actual)
Sponsor and investigators
- Lead sponsor
- Philogen S.p.A.
- Sponsor type
- Industry (pharma, biotech, devices)
- Collaborators
- Immatics Biotechnologies GmbH
- Responsible party
- Sponsor
- Investigators
- Jürgen C. Becker, Prof., Principal investigator, Medical University of Graz
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02054884
- Sponsor's protocol ID
- PH-F16IL2TAXO-03/12
- Status last verified
- May 2018
- First submitted
- 31 Jan 2014
- Last updated
- 18 May 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 May 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT02054884
- Acronym / sponsor ID
- PH-F16IL2TAXO-03/12
- Conditions
- Merkel Cell Carcinoma
- Keywords
- Interleukin, IL2, F16, monoclonal, antibody, cytokine Paclitaxel, Merkel cell carcinoma
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Lack of enrollment
- Enrolment
- 13 participants (actual)
- Lead sponsor
- Philogen S.p.A.Industry (pharma, biotech, devices)
- Collaborators
- Immatics Biotechnologies GmbH
- Study start
- 25 Oct 2013 (actual)
- Primary completion
- 31 Dec 2016 (actual)
- Study completion
- 15 Dec 2017 (actual)
- First posted
- 4 Feb 2014 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Detailed description
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).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Arm A: F16IL2 in combination with paclitaxel | Experimental | Drug: Arm A: F16IL2 in combination with paclitaxel |
| Arm B: Paclitaxel | Experimental | Drug: Arm B: Paclitaxel |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (13 listed)
- 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;.
Key exclusion criteria (23 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Arm A: F16IL2 in combination with paclitaxelIntravenous (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. | Drug | Arm A: F16IL2 in combination with paclitaxel |
| Arm B: PaclitaxelIntravenous (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. | Drug | Arm B: Paclitaxel |
Primary outcome
Efficacy of F16IL2 in combination with paclitaxel vs. paclitaxel monotherapy (RECIST v1.1, irRC)
Time frame: 12 months
3 secondary outcomes
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
Results and safety
The study was stopped early (reason given: Lack of enrollment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 May 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Jürgen C. Becker, Prof. principal investigator
Medical University of Graz
8 sites in 6 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Arm A: F16IL2 in combination with paclitaxel and Arm B: Paclitaxel in people with Merkel Cell Carcinoma, run by Philogen S.p.A. at 8 sites in 6 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 13 inclusion and 23 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: stopped early, as of the sponsor's last update on 18 May 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in Germany, Austria, Denmark, France, Spain and 1 more country. 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 phase mean?
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?
The study was stopped early (reason given: Lack of enrollment). 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?
Efficacy of F16IL2 in combination with paclitaxel vs. paclitaxel monotherapy (RECIST v1.1, irRC) (time frame: 12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 18 May 2018.