L19TNFα in Combination With Doxorubicin in Patients With Advanced Solid Tumours
Advanced Solid Tumors Amenable to Anthracycline Therapy
Sarcoma, Breast Cancer, Lung Carcinomas, and Gynecological Cancer Amenable to Anthracycline Therapy
|Study Design:||Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Tumor-targeting Human L19TNFα Monoclonal Antibody-cytokine Fusion Protein in Combination With Doxorubicin in Patients With Advanced Solid Tumours|
- Dose limiting toxicity (DLT) [ Time Frame: From day 1 to day 29 ] [ Designated as safety issue: Yes ]
To assess the safety, including maximum tolerated dose (MTD), recommended dose (RD) and dose limiting toxicity (DLT) of L19TNFα in combination with doxorubicin, the following will be considered:
- Adverse Events (AEs) assessment based on CTCAE v.4.03, including DLT assessment.
- Standard laboratory (haematology, biochemistry and urinalysis) parameters.
- Physical examination findings including assessment of vital signs and physical measurements (blood pressure, heart rate, body weight).
- Pharmacokinetics assessment of L19TNFα [ Time Frame: At day 1 of week 1 ] [ Designated as safety issue: No ]
- Human anti-fusion protein antibodies (HAFA) levels [ Time Frame: 1) at day 1, 2) at day 22, 3) at day 43, 4) at day 64, 5) at day 85, 6) at day 106, 7) from day 31 up to day 143, 8) from day 73 up to day 185 ] [ Designated as safety issue: Yes ]Investigate the potential induction of human anti-fusion protein antibodies (HAFA) through standard laboratory analysis.
- Objective response rate (ORR) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]To investigate the antitumor activity
- Median progression free survival (mPFS) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]To investigate the antitumor activity
- Median overall survival (OS) [ Time Frame: Up to 1 year ] [ Designated as safety issue: No ]To investigate the antitumor activity
|Study Start Date:||January 2013|
|Estimated Study Completion Date:||June 2018|
|Estimated Primary Completion Date:||June 2018 (Final data collection date for primary outcome measure)|
Experimental: L19TNFα + doxorubicin
Only one arm is specified. Patients will be treated in three cohorts with 3 different dosages of L19TNFα in combination with 60 mg/m2 of doxorubicin, according to the following study design:
cohort 1 --> 10.4 μg/kg L19TNFα + doxorubicin; cohort 2 --> 13 μg/kg L19TNFα + doxorubicin; cohort 3 --> 17 μg/kg L19TNFα + doxorubicin.
L19TNFα will be administered as a 2 hours i.v. infusion on days 1, 3, and 5 of each 3-week cycle.Drug: Doxorubicin
Doxorubicin will be administered as a 15 minutes i.v. infusion on day 1 of each 3-week cycle prior L19TNFα administration.
In the clinical trial 3-6 patients will be assigned to L19TNFalfa at one of the following sequential dose levels (10.4 µg/kg, 13 µg/kg and 17 µg/kg) in combination with a fixed dose of doxorubicin.
The RD will be defined following a traditional 3+3 design. The dose escalation will continue until the MTD is found, that is until at least two patients among a cohort of three to six patients experience a dose limiting toxicity (DLT).
Please refer to this study by its ClinicalTrials.gov identifier: NCT02076620
|Contact: Teresa Hemmerle, Dr||0039 0577 email@example.com|
|Contact: Serena Bettarini, Dr||0039 0577 firstname.lastname@example.org|
|Contact: Christoph Schliemann, Dr|
|Principal Investigator: Christoph Schliemann, Dr|
|Fondazione IRCCS Istituto Nazionale dei Tumori||Recruiting|
|Contact: Filippo De Braud, Dr|
|Principal Investigator: Filippo De Braud, Dr|
|Principal Investigator:||Filippo De Braud, Dr||Fondazione IRCCS Istituto Nazionale dei Tumori|
|Principal Investigator:||Christoph Schliemann, Dr||Universitätsklinikum Münster|