- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01253837
L19TNFα in Patients With Advanced Solid Tumors
Phase I/II Study of the Tumor-targeting Human L19TNFα Monoclonal Antibody-cytokine Fusion Protein in Patients With Advanced Solid Tumors
Study Overview
Detailed Description
Study Type
Enrollment (Anticipated)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Ancona, Italy
- A.O. UNIVERSITARIA OSPEDALI RIUNITI - OSPEDALE UMBERTO I DI ANCONA - ANCONA (Italy)
-
Milan, Italy
- European Istitue of Oncology Milan (Italy)
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- 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.
Exclusion Criteria:
- 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.
- Known history of allergy to TNFα or other intravenously administered human proteins/peptides/antibodies.
- Chemotherapy, radiation therapy or therapy with an investigational agent within 4 weeks prior start of study treatment.
- Previous in vivo exposure to monoclonal antibodies for biological therapy in the 6 weeks before administration of study treatment.
- Growth factors or immunomodulatory agents within 7 days prior to the administration of the study treatment.
- Subject requires or is taking corticosteroids or other immunosuppressant drugs on a long-term basis. Limited use of corticosteroids to treat or prevent acute hypersensitivity reactions is not considered an exclusion criterion.
- Concurrent therapy with warfarin at doses greater than 1 mg/day or equivalent doses of other coumarin derivatives.
- Participation in another interventional clinical trial during participation in this trial.
- Expectation that the subject will not be able to complete at least 6 weeks of therapy.
- Any conditions that in the opinion of the Investigator could hamper compliance with the study protocol.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: TREATMENT
- Allocation: NA
- Interventional Model: SINGLE_GROUP
- Masking: NONE
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
EXPERIMENTAL: L19TNFa
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. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Phase I: Determination of the Maximum Tolerated Dose (MTD) and Recommended Dose (RD)
Time Frame: day 1-29
|
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)
Time Frame: within day 42
|
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 Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Investigation of serum concentrations of L19TNFα (pharmacokinetic properties)
Time Frame: day 1-5
|
day 1-5
|
|
Investigation of the induction of human anti-fusion protein antibody (HAFA)
Time Frame: 1-16 months
|
1-16 months
|
|
Investigation of early signs of anti-tumor activity of L19TNFα
Time Frame: 14 months
|
Investigation of early signs of anti-tumor activity of L19TNFα as measured by Objective Response Rate (ORR) at the end of cycle 2, median Progression-Free Survival (PFS) and median Overall Survival (OS).
|
14 months
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Filippo De Braud, Dr., European Istitute of Oncology Milan (Italy)
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
- colorectal cancer
- antibody
- monoclonal
- tumor targeting
- L19
- TNFa
- 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
Other Study ID Numbers
- PH-L19TNFα-02/07
- 2007-001157-26 (EUDRACT_NUMBER)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Colorectal Cancer
-
University of California, San FranciscoCompletedStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
Fred Hutchinson Cancer CenterNational Cancer Institute (NCI)TerminatedRectal Cancer | Colon Cancer | Cancer Survivor | Colorectal Adenocarcinoma | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
University of Southern CaliforniaNational Cancer Institute (NCI)TerminatedStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterNational Cancer Institute (NCI)Active, not recruitingStage IV Colorectal Cancer AJCC v8 | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC... and other conditionsUnited States
-
M.D. Anderson Cancer CenterRecruitingColorectal Adenocarcinoma | Stage IVA Colorectal Cancer AJCC v8 | Stage IVB Colorectal Cancer AJCC v8 | Stage IVC Colorectal Cancer AJCC v8 | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage... and other conditionsUnited States
-
Wake Forest University Health SciencesNational Cancer Institute (NCI)CompletedCancer Survivor | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage IIA Colorectal Cancer AJCC v8 | Stage IIB Colorectal... and other conditionsUnited States
-
Sidney Kimmel Cancer Center at Thomas Jefferson...United States Department of DefenseActive, not recruitingColorectal Adenoma | Stage III Colorectal Cancer AJCC v8 | Stage IIIA Colorectal Cancer AJCC v8 | Stage IIIB Colorectal Cancer AJCC v8 | Stage IIIC Colorectal Cancer AJCC v8 | Stage 0 Colorectal Cancer AJCC v8 | Stage I Colorectal Cancer AJCC v8 | Stage II Colorectal Cancer AJCC v8 | Stage IIA Colorectal... and other conditionsUnited States
-
City of Hope Medical CenterRecruitingColorectal Neoplasms | Colorectal Cancer | Colorectal Adenocarcinoma | Colorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Neoplasms Malignant | Colorectal Cancer Stage IUnited States, Japan, Italy, Spain
-
University of Roma La SapienzaCompletedColorectal Cancer Stage II | Colorectal Cancer Stage III | Colorectal Cancer Stage IV | Colorectal Cancer Stage 0 | Colorectal Cancer Stage IItaly
-
University of Southern CaliforniaNational Cancer Institute (NCI); AmgenTerminatedStage IV Colorectal Cancer AJCC v7 | Stage IVA Colorectal Cancer AJCC v7 | Stage IVB Colorectal Cancer AJCC v7 | Colorectal Adenocarcinoma | RAS Wild Type | Stage III Colorectal Cancer AJCC v7 | Stage IIIA Colorectal Cancer AJCC v7 | Stage IIIB Colorectal Cancer AJCC v7 | Stage IIIC Colorectal Cancer...United States