Combination Therapy of F16IL2 and Paclitaxel in Solid Tumour Patients
Phase Ib/II Study of the Tumour-targeting Human F16IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Paclitaxel in Patients With Advanced Solid Tumours
2 other identifiers
interventional
48
1 country
5
Brief Summary
This Phase Ib/II study is an open label, multicenter study. The study is divided in two parts: Phase I: an open-label, dose escalation study of F16IL2 in combination with paclitaxel for patients with solid tumours, bladder cancer, breast cancer, metastatic melanoma, mesothelioma, NSCLC, prostate cancer and sarcoma amenable to taxane therapy. Phase II: a prospective, single-arm, multicentre study of a fixed dose of F16IL2 in combination with paclitaxel, equivalent to stage 1 of the Simon two-stage phase II design, for patients with metastatic melanoma, breast cancer and NSCLC amenable to taxane therapy.
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at P50-P75 for phase_1
Started Aug 2008
Longer than P75 for phase_1
5 active sites
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
August 6, 2008
CompletedFirst Submitted
Initial submission to the registry
May 25, 2010
CompletedFirst Posted
Study publicly available on registry
May 31, 2010
CompletedPrimary Completion
Last participant's last visit for primary outcome
April 7, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
April 7, 2014
CompletedApril 15, 2022
April 1, 2022
5.7 years
May 25, 2010
April 8, 2022
Conditions
Keywords
Outcome Measures
Primary Outcomes (2)
To establish the maximum tolerated dose (MTD) and the recommended dose (RD) of F16IL2 when administered in combination with paclitaxel (Phase I).
Safety evaluations performed days 1 through 28, including AEs, SAEs and standard laboratory assessments graded according to the NCI-CTCAE, v3, will be used for determination of dose limiting toxicity (DLT).
28 days
To investigate the efficacy of F16IL2, in terms of objective response rate in combination with paclitaxel in metastatic melanoma, breast cancer and NSCLC patients amenable to taxane therapy (Phase II)
The primary efficacy endpoint is the proportion of patients achieving a Tumour Response at week 8.
8 weeks
Secondary Outcomes (5)
To investigate the safety and tolerability of F16IL2 and paclitaxel when given as a combination (Phase I/II).
8 weeks
Investigate pharmacokinetics of F16IL2 and paclitaxel when given as a combination.
2 weeks
Human anti-fusion protein antibodies
18 months
Antitumor activity
12 months
Assessment of median progression-free survival and median overall survival.
12 months
Study Arms (1)
F16IL2 in combination with paclitaxel
EXPERIMENTALInterventions
Intravenous (i.v.) infusions of F16IL2 (Dose escalation: from 5 to 35 MioIU, the dose could be further increased until MTD is reached, following a pharmacokinetic-guided design) on days 1, 8, 15, 29, 36 and 43 over 60 minutes via automated device (perfusor), followed by a 1 hour i.v. infusion of paclitaxel (Dose escalation: from 60 up to 90 mg/m2) on days 1, 8, 15, 29, 36 and 43. Patients with objective tumor responses or stable disease will receive additional combination therapy for a maximum of 6 months, or until disease progression, unacceptable toxicity or withdrawal of consent.
Eligibility Criteria
You may qualify if:
- For Phase I, cohorts 1 to 8, of the study:
- For patient of Phase I cohort 1, i.e. those patients receiving F16IL2 alone, patients must not be amenable to therapy with paclitaxel/taxanes but must be considered by the Principal Investigator to be suitable candidates for F16IL2 therapy alone.
- Histologically or cytologically confirmed solid cancer with/without evidence of locally advanced or metastatic disease.
- For advanced solid cancer patients, patients may have received previous chemotherapy or radiation therapy, but they must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
- For Phase I, cohorts 9 onwards:
- Histologically or cytologically confirmed bladder cancer, breast cancer, unresectable metastatic (stage IV) non-uveal melanoma, mesothelioma, NSCLC, prostate cancer or sarcoma.
- Prior therapies for metastatic disease are allowed, but patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
- For breast cancer patients only: patients not suitable for trastuzumab therapy (i.e., no evidence of HER2-overexpressing disease, or trastuzumab therapy exhausted in HER2-overexpressing disease).
- For Phase II of the study:
- Histologically or cytologically confirmed breast cancer, unresectable metastatic (stage IV) non-uveal melanoma, or NSCLC.
- Prior therapies for metastatic disease are allowed, but patients must be amenable for paclitaxel treatment according to the discretion of the principal investigator.
- For breast cancer patients only: patients not suitable for trastuzumab therapy (i.e., no evidence of HER2-overexpressing disease, or trastuzumab therapy exhausted in HER2-overexpressing disease).
- For phase I and II of the study:
- Patients aged ≥ 18 years.
- Prior radiation therapy is allowed, if the irradiated area is not the only source of measurable or assessable disease.
- +13 more criteria
You may not qualify if:
- For metastatic melanoma patients: Primary ocular melanoma
- Previous or concurrent cancer that is distinct in primary site or histology from the cancer being evaluated in this study, or any cancer curatively treated \< 2 years prior to study entry, except cervical carcinoma in situ, treated basal cell carcinoma, superficial bladder tumors (TA, TIs \& TI).
- Presence of active infections (e.g. requiring antibiotic therapy) 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. If patient is symptomatic, negative CT scan within two months before study beginning is required. However, presence of controlled brain metastases (i.e., evaluated as SD of PR after radiotherapy) is allowed.
- History of chronic hepatitis B or C, or chronic active hepatitis or active autoimmune diseases.
- History within the last year 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 MUGA, ECHO or ECG investigations.
- Uncontrolled hypertension.
- Ischemic peripheral vascular disease (Grade IIb-IV).
- Severe rheumatoid arthritis.
- Severe diabetic retinopathy.
- History of allograft or stem cell transplantation.
- Major trauma including surgery within 4 weeks of administration of study treatment.
- +9 more criteria
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Philogen S.p.A.lead
Study Sites (5)
A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (AN) (Italy)
Ancona, Italy
Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)
Meldola, Italy
European Institute of Oncology
Milan, 20141, Italy
A.O. UNIVERSITARIA POLICLINICO DI MODENA (Italy)
Modena, Italy
Azienda Ospedaliera Universitaria Senese
Siena, Italy
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Chiara Matilde Catania, Dr
European Institute of Oncology Milan (Italy)
Study Design
- Study Type
- interventional
- Phase
- phase 1
- Allocation
- NA
- Masking
- NONE
- Purpose
- TREATMENT
- Intervention Model
- SINGLE GROUP
- Sponsor Type
- INDUSTRY
- Responsible Party
- SPONSOR
Study Record Dates
First Submitted
May 25, 2010
First Posted
May 31, 2010
Study Start
August 6, 2008
Primary Completion
April 7, 2014
Study Completion
April 7, 2014
Last Updated
April 15, 2022
Record last verified: 2022-04