Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer (CHIP)
|Recurrent Ovarian Cancer||Drug: Interferon Alfa-2b Biological: p53 SLP||Phase 1 Phase 2|
|Study Design:||Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
|Official Title:||Chemo-Immunotherapy, Gemcitabine With Pegylated Interferon Alpha-2b (Peg-Intron) With and Without p53 Synthetic Long Peptide (p53 SLP) Vaccine, for Patients With Platinum Resistant Ovarian Cancer CHIP Trial|
- Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ]During the trial we will measure the incidence and severity of all side effects (according to CTC version 4.0). The change in immunogenecity will be measured according to the induction of p53-specific T cells upon treatment.
- Clinical outcome (response (RECIST 1.1) [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ]Clinical outcome will be tested by analyzing CA125 in sera and tumor size at CT (by RECIST 1.1)and time from start treatment until death
- The effect of this new treatment combination on the immune system [ Time Frame: Before treatment, after two months and after 6 months after treatment ]Changes in plasma signature and tumor tissue will be measured
- progression free survival [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ]
- overall survival [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ]
|Study Start Date:||August 2011|
|Primary Completion Date:||January 2014 (Final data collection date for primary outcome measure)|
No Intervention: Group 1
Patients will receive standard care (gemcitabine)
Experimental: Group 2
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron)
Drug: Interferon Alfa-2b
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
Experimental: Group 3
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin
Drug: Interferon Alfa-2b
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabineBiological: p53 SLP
8.2.3 The p53 SLP vaccine consists of 9 synthetic 25-30 amino acids long overlapping peptides, spanning amino acids 70-235 of the wt-p53 protein (patent number WO2008147186). Peptides are prepared at the GMP facility of the Department of Clinical Pharmacy and Toxicology of the LUMC. At the day of immunization peptides (0.3 mg/peptide) were dissolved in dimethyl sulfoxide (DMSO, final concentration 20%) admixed with 20 mM phosphate buffer (pH7.5) and emulsified with an equal volume of Montanide ISA-51.The vaccine (2.7mL) is administered subcutaneously.
Recurrent ovarian cancer has a dismal prognosis and there is a pressing need to identify more efficient therapies. Ovarian cancer is highly immunogenic and good survival is tightly linked to the presence of tumor-infiltrating T cells and the absence of immunosuppressive immune cells. This anti-tumor immune response might be primed by chemotherapy.
Gemcitabine has immune-modulatory properties in addition to its direct cytotoxic effect in platinum resistant ovarian cancer. Additionally, Peg-Intron allows the full maturation of dendritic cells, thereby enhancing the anti-tumor response. Moreover, the tumor-associated self-antigen p53 is commonly over-expressed in ovarian cancer and can serve as a target for immunotherapy. Therefore, chemo-immunotherapy with gemcitabine and Peg-Intron plus/minus p53 SLP vaccination seems an attractive treatment for recurrent, p53+ ovarian cancer patients.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01639885
|Leiden University Medical Center|
|Leiden, Netherlands, 2333 ZA|
|Principal Investigator:||Judith R Kroep, MD, PhD||Leiden University Medical Center|