Combination Therapy of L19IL2 and Gemcitabine in Advanced Pancreatic Cancer Patients
Systemic treatment for advanced, non-resectable pancreatic cancer still having minimal impact on the survival of patients. Even with the application of more potent gemcitabine-based regimens, survival of more than 1 year is uncommon for advanced disease. Accordingly, there is substantial unmet needs for the improvement of treatment options. The combination and simultaneous application of tumor-targeted L19IL2 with gemcitabine could result in improved anti-cancer efficacy, based on preliminary clinical and strong preclinical data.
The primary purpose of this Phase I study is to define a safe and potentially more active treatment regimen of L19IL2 (escalating doses) combined with gemcitabine for advanced pancreatic cancer patients. Also, early signs of anticancer responses of the L19IL2/gemcitabine regimen will be assessed and compared to historical controls (gemcitabine monotherapy).
|Pancreatic Cancer Patients Diagnosed With Locally Advanced or Metastatic Pancreatic Cancer Not Amenable to Curative Surgical Resection.||Drug: L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine||Phase 1|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
|Official Title:||Phase I Study of the Tumor-targeting Human L19IL2 Monoclonal Antibody-cytokine Fusion Protein in Combination With Gemcitabine in Patients With Advanced Pancreatic Cancer|
- Maximum tolerated dose and the preliminary tolerability profile. [ Time Frame: 49 days ]Establishment of the maximum tolerated dose (MTD) and the preliminary tolerability profile of L19IL2 and gemcitabine including the recommended phase II doses (RD) when used in combination.
- Pharmacokinetics [ Time Frame: 4 weeks ]Investigation of the pharmacokinetics of L19IL2 and gemcitabine when given as a combination.
- Human anti-fusion protein antibodies [ Time Frame: 18 months ]Investigation of the induction of human anti-fusion protein antibodies (HAFA) levels.
- Antitumor activity [ Time Frame: 18 months ]Investigation of the antitumor activity of the combination of L19IL2 and gemcitabine in previously treated and untreated locally advanced or metastatic pancreatic cancer patients.
|Study Start Date:||June 2007|
|Study Completion Date:||November 2014|
|Primary Completion Date:||November 2014 (Final data collection date for primary outcome measure)|
Therapy of L19IL2 and Gemcitabine
Dose escalation study. Part A) Gemcitabine dose escalation. Part B) L19IL2 dose escalation.
Drug: L19IL2 monoclonal antibody-cytokine fusion protein in combination with gemcitabine
Part A) Patient cohorts will sequentially be assigned to 800 or 1,000 mg/m2 of gemcitabine. gemcitabine will be given in combination with a fixed dose of L19IL2. Part B) Patient cohorts will sequentially be assigned to 10, 15,22.5,30 or 37,5 MioIU IL2 equivalents of L19IL2. L19IL2 will be given in combination with gemcitabine at the dose recommended from Part A. Should the MTD of L19IL2 not be reached within the planned cohorts listed above, the dose of L19IL2 will be further increased following 7.5 MioIU increasing steps.
Induction treatment: Intravenous (i.v.) infusions of L19IL2 on days 1,3,5,22,24, 26,43,45,47, followed by i.v. infusions of gemcitabine on days 1,8,15,22,29,36,43. Maintenance treatment: Patients with objective tumor responses or stable disease will receive up to 4 cycles of maintenance treatment, starting on day 57: i.v. infusions of L19IL2 on days 1 (day 57), 8,15, followed by an i.v. infusion of gemcitabine. Treatment cycles will be repeated on day 29.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01198522
|Campus Charité Virchow Klinikum|
|National Center for Tumor Diseases (NCT)|
|Mater Salutis Hospital|
|European Institute of Oncology|
|Azienda Ospedaliera Universitaria Senese|