L19TNFα in Patients With Advanced Solid Tumors
This study has been completed.
Information provided by (Responsible Party):
First received: December 2, 2010
Last updated: September 22, 2011
Last verified: September 2011
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.
||Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
||Phase I/II Study of the Tumor-targeting Human L19TNFα Monoclonal Antibody-cytokine Fusion Protein in Patients With Advanced Solid Tumors
Primary Outcome Measures:
- Phase I: Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) [ Time Frame: day 1-29 ] [ Designated as safety issue: Yes ]
Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD) of L19TNFα.
- Phase II: Investigation of the anti-cancer activity of L19TNFα as measured by Objective Response Rate (ORR) [ Time Frame: within day 42 ] [ Designated as safety issue: No ]
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.
Secondary Outcome Measures:
| Estimated Enrollment:
| Study Start Date:
| Study Completion Date:
| Primary Completion Date:
||May 2011 (Final data collection date for primary outcome measure)
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.
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.
The primary purpose of this Phase I/II study is to define a safe and potentially active treatment regimen of L19TNFα as a monotherapy and to evaluate the antitumor activity of this regimen in relapsed metastatic colorectal cancer subjects, for whom standard treatment options are exhausted. L19TNFα is an investigational drug that specifically and effectively binds to ED-B, which is abundantly expressed in cancer tissue. Accordingly, treatment should result in a high and long-lasting intratumoral accumulation of biologically active rh-TNFα. Although combined therapies of TNFα with cytotoxic drugs (e.g. melphalan) seem to be strikingly more active against sarcoma and melanoma than with TNFα alone - at least for the ILP setting it seems possible that the repeated intratumoral delivery of TNFα via L19TNFα might produce additional biologic effects, such as the induction of an immunologic antitumor response or the sustained inhibition of tumor-associated angiogenesis (Lejeune, 2006), that potentially could benefit advanced cancer subjects.
|Ages Eligible for Study:
||18 Years and older (Adult, Senior)
|Genders Eligible for Study:
|Accepts Healthy Volunteers:
- 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.
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01253837
|A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (Italy)
|Ancona, Italy |
|European Istitue of Oncology Milan (Italy)
|Milan, Italy |
||Filippo De Braud, Dr.
||European Istitute of Oncology Milan (Italy)
History of Changes
|Other Study ID Numbers:
|Study First Received:
||December 2, 2010
||September 22, 2011
||Italy: National Institute of Health
Italy: Ethics Committee
Keywords provided by Philogen S.p.A.:
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.
Additional relevant MeSH terms:
ClinicalTrials.gov processed this record on October 28, 2016
Digestive System Neoplasms
Neoplasms by Site
Digestive System Diseases