Combination Therapy of F16IL2 and Doxorubicin in Solid Tumour Patients

NCT01131364 | Terminated Phase 1

• 2 other identifiers: PH-F16IL2DOXO-04/072007-006176-11
• Study Type: interventional
• Target: 29
• Locations: 1 country
• Sites: 5

Brief Summary

This Phase Ib/II study is an openlabel, multicenter study for patients with solid tumors and breast cancer amenable to anthracyclin therapy. The study is divided in two parts: Phase I: an open-label, dose escalation study of F16IL2 in combination with doxorubicin for patients with solid tumors. Phase II: a prospective, single-arm, multicentre study of a fixed dose of F16IL2 in combination with doxorubicin, equivalent to stage 1 of the Simon two-stage phase II design, for patients with breast cancer amenable to anthracyclin therapy.

Conditions

Advanced Solid Tumor; Breast Cancer

Keywords

Interleukin; IL2; F16; monoclonal; antibody; cytokine; doxorubicin; breast cancer; solid tumour; Phase I: Advanced Solid Tumour Patients; Phase II: Breast Cancer Patients Amenable to anthracyclin Therapy

Outcome Measures

Primary Outcomes (2)

• Maximum tolerated and recommended dose (MTD) (RD)

  Phase I: To establish the maximum tolerated dose (MTD) and the RD of F16IL2 when administered in combination with doxorubicin.

  28 days

• Efficacy of F16IL2 in combination with doxorubicin

  Phase II: To investigate the efficacy in terms of objective response rate of F16IL2 in combination with doxorubicin in breast cancer patients amenable to anthracyclin therapy.

  8 weeks

Secondary Outcomes (6)

• Safety/Tolerability

  8 weeks

• Pharmacokinetics of F16IL2

  2 weeks

• Human anti-fusion protein antibodies

  18 months

• Antitumor activity

  12 months

• Median progression-free survival

  12 months

Study Arms (1)

F16IL2 in combination with doxorubicin

EXPERIMENTAL

Drug: F16IL2 in combination with doxorubicin

Interventions

F16IL2 in combination with doxorubicin DRUG

Intravenous (i.v.) infusions of F16IL2 (Dose escalation: from 5 up to 25 MioIU) on days 1, 8, 15, 29, 36 and 43 over 60 minutes via automated device (perfusor), followed by a 30-minute i.v. infusion of doxorubicin (Dose escalation: from 20 up to 25 mg/m2) on Days 1, 8, 15 29, 36 and 43. Patients with objective tumor responses or stable disease will receive repeated cycles of treatment starting on Day 56. Patients will receive additional cycles of combination therapy for a maximum of 6 months, or until disease progression, unacceptable toxicity or withdrawal of consent.

F16IL2 in combination with doxorubicin

Eligibility Criteria

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

You may qualify if:

• For Phase I 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 doxorubicin/anthracycline 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 (Appendix B).
• For advanced solid cancer patients, patients may have received previous chemotherapy or radiation therapy, but they must be amenable for doxorubicin treatment according to the discretion of the principal investigator.
• For Phase II of the study:
• Histologically or cytologically confirmed breast cancer.
• Previous anthracycline therapy, including liposomal doxorubicin, for metastatic and/or adjuvant disease is allowed. However, patients must not have received a cumulative anthracycline dose of more than 300 mg/m2 of doxorubicin or of more than 600 mg/m2 of epirubicin or pegylated or non-pegylated liposomal doxorubicin, prior to study entry, in order to avoid anthracycline-associated cardiotoxicity.
• Prior radiation therapy is allowed, if the irradiated area is not the only source of measurable or assessable disease.
• 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.
• Patients recruited to Phase I, cohort I must be considered not suitable to doxorubicin/anthracycline therapy in the opinion of the Principal Investigator.
• Only for phase I, patients must not have received more than 300 mg/m2 of doxorubicin or 500 mg/m2 of epirubicin in prior chemotherapy.
• Patients must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria (see Section APPENDIX A). This lesion must not have been irradiated during previous treatments.
• All acute toxic effects (excluding alopecia) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to National Cancer Institute (NCI) Common Terminology Criteria for Adverse Events (CTCAE) (v3.0) Grade ≤ 1.

You may not qualify if:

• 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. However, presence of controlled brain metastases (i.e., evaluated as SD of PR after radiotherapy) is allowed.
• Known to have a second uncontrolled cancer of other primary origin within the last 5 years.
• 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.
• Recovery from major trauma including surgery within 4 weeks of administration of study treatment.
• Known history of allergy to IL-2, doxorubicin, 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 judgment of the principal investigator or a designated associate.

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

Location

Irst - Istituto Scientifico Romagnolo Per Lo Studio E La Cura Dei Tumori - Meldola (Fc)

Meldola, Italy

Location

European Institute of Oncology

Milan, Italy

Location

A.O. UNIVERSITARIA POLICLINICO DI MODENA (Italy)

Modena, Italy

Location

Azienda Ospedaliera Universitaria Senese

Siena, Italy

Location

MeSH Terms

Conditions

Breast Neoplasms

Interventions

Doxorubicin

Condition Hierarchy (Ancestors)

Neoplasms by Site; Neoplasms; Breast Diseases; Skin Diseases; Skin and Connective Tissue Diseases

Intervention Hierarchy (Ancestors)

Daunorubicin; Anthracyclines; Naphthacenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Aminoglycosides; Glycosides; Carbohydrates

Study Officials

• Chiara Matilde Catania, Dr

  European Institute of Oncology Milan, Italy

  PRINCIPAL INVESTIGATOR

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 26, 2010
• Study Start: June 1, 2008
• Primary Completion: March 1, 2012
• Study Completion: December 1, 2012
• Last Updated: February 25, 2014

Record last verified: 2014-02

Locations

IT (5)