L19TNFα in Patients With Advanced Solid Tumors

NCT01253837 | Completed Phase 1

• 2 other identifiers: PH-L19TNFα-02/072007-001157-26
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 2

Brief Summary

The recombinant human fusion protein L19TNFα was created with the intention to overcome the systemic toxicity of TNFα by directly targeting it to tumor tissues. Tumor-targeted L19TNFα would result in high and sustained intralesional bioactive TNFα concentrations.

Conditions

Solid Tumors; Colorectal Cancer

Keywords

L19; antibody; monoclonal; tumor targeting; TNFa; colorectal cancer; Phase I: Patients with relapsed or refractory locally advanced or metastatic solid tumors not amenable to standard systemic therapy.; Phase II: Patients with relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard systemic therapy.

Outcome Measures

Primary Outcomes (2)

• Phase I: Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD)

  Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of L19TNFα.

  day 1-29

• Phase II: Investigation of the anti-cancer activity of L19TNFα as measured by Objective Response Rate (ORR)

  Investigation of the anti-cancer activity of L19TNFα as monotherapy as measured by the Objective Response Rate (ORR) at the end of cycle 2 in subjects with relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard systemic therapy.

  within day 42

Secondary Outcomes (3)

• Investigation of serum concentrations of L19TNFα (pharmacokinetic properties)

  day 1-5

• Investigation of the induction of human anti-fusion protein antibody (HAFA)

  1-16 months

• Investigation of early signs of anti-tumor activity of L19TNFα

  14 months

Study Arms (1)

L19TNFa

EXPERIMENTAL

Phase I: Prospective, open-label, dose escalation study. Phase II: Prospective, single-arm, open-label study, equivalent to the stage 1 of the Simon two-stage phase II design.

Drug: L19TNFa

Interventions

L19TNFa DRUG

Phase I: Sequential assignment of Patient cohorts to one of six dose levels of L19TNFa: 1.3, 2.6, 5.2, 7.8, 10.4, 13.0 µg/kg. Phase II: The Recommended Dose (RD) of 13.0 µg/kg of L19TNFα determined in Phase I. Schedule: Infusions of L19TNFα on days 1, 3 and 5 of each 21-day cycle. Patients may remain on treatment for a maximum of six 21-day cycles.

L19TNFa

Eligibility Criteria

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

You may qualify if:

• Phase I: histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic solid tumor of any origin, not amenable to standard therapy.
• Phase II: histologically or cytologically confirmed relapsed or refractory locally advanced or metastatic colorectal cancer not amenable to standard therapy.
• For both phase I and II:
• Subjects aged ≥ 18 years.
• ECOG performance status ≤ 2.
• Subjects must have at least one unidimensionally measurable lesion by computed tomography as defined by RECIST criteria (see Section 8) or tumour markers parameters of disease such as PSA and CA125 for Prostate cancer and Ovarian cancer, respectively. This lesion must not have been irradiated during previous treatments.
• Absolute neutrophil count (ANC) ≥ 1.5 x 10\^9/L, platelets ≥ 100 x 10\^9/L, and haemoglobin (Hb) ≥ 9.5 g/dl.
• All acute adverse effects (excluding alopecia) of any prior therapy (including surgery, radiation therapy, chemotherapy) must have resolved to ≤ Grade 1, except elevated liver transaminases judged to be associated with tumor infiltration (see below) (graded according to National Cancer Institute \[NCI\] Common Terminology Criteria for Adverse Events, version 3.0 \[CTCAE, v.3.0\]).
• Alkaline phosphatase (ALP), alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) ≤ 2.5 x upper limit of normal (ULN), and total bilirubin ≤ 2.0 mg/gL unless liver involvement by the tumor, in which case the transaminase levels up to 5 x ULN are allowed.
• Creatinine ≤ 1.5 ULN or 24 h creatinine clearance ≥ 60 mL/min.
• Testing negative for acute or chronic infection with hepatitis B or C virus, or human immunodeficiency virus 1 or 2.
• Negative pregnancy test for females of childbearing potential at the screening visit.
• Commitment from subject to practice medically appropriate/acceptable method of birth control (e.g., hormonal, condoms or other adequate barrier controls, intrauterine contraceptive device, or sterilization) beginning at the screening visit and continuing until 3 months following the last treatment with study drug.
• Able to provide written Informed Consent.

You may not qualify if:

• Breastfeeding women.
• Presence of active infections (e.g. requiring antimicrobial therapy) or other severe concurrent disease, which, in the opinion of the Investigator, would place the subject at undue risk or interfere with the study.
• Known brain metastases or signs and/or symptoms suggestive of brain metastases.
• Known cancer of other primary origin (excluding Stage I non-melanoma skin cancer) within the prior 5 years.
• Active autoimmune disease.
• Cardiac disease as manifested by any of the following:
• \> Grade II heart failure, graded per New York Heart Association (NYHA) criteria.
• Unstable angina pectoris.
• Acute or subacute coronary syndromes, including myocardial infarction, occurring with 1 year prior to study treatment.
• Arrhythmia needing continuous treatment.
• Ejection fraction less than the institutional lower limit of normal as assessed by multigated radionuclide angiography (MUGA) scan or echocardiogram.
• Uncontrolled hypertension.
• Ischemic peripheral vascular disease (Grade IIb-IV).
• Severe diabetic retinopathy.
• Major surgery or trauma within 4 weeks prior to start of study treatment.

Sponsors & Collaborators

• Philogen S.p.A.: lead
• InnoPharma Inc.: collaborator
• Eudax S.r.l.: collaborator

Study Sites (2)

A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (Italy)

Ancona, Italy

Location

European Istitue of Oncology Milan (Italy)

Milan, Italy

Location

MeSH Terms

Conditions

Colorectal Neoplasms

Condition Hierarchy (Ancestors)

Intestinal Neoplasms; Gastrointestinal Neoplasms; Digestive System Neoplasms; Neoplasms by Site; Neoplasms; Digestive System Diseases; Gastrointestinal Diseases; Colonic Diseases; Intestinal Diseases; Rectal Diseases

Study Officials

• Filippo De Braud, Dr.

  European Istitute 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: December 2, 2010
• First Posted: December 3, 2010
• Study Start: September 1, 2007
• Primary Completion: May 1, 2011
• Study Completion: September 1, 2011
• Last Updated: September 23, 2011

Record last verified: 2011-09

Locations

IT (2)