Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer

Recurrent Ovarian Cancer Clinical Trial

— CHIP  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01639885
• Other study ID #: CHIP trial
• Secondary ID: 2010-023124-24
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: April 16, 2012
• Last updated: January 6, 2014
• Start date: August 2011

Study information

• Verified date: January 2014
• Source: Leiden University Medical Center
• Contact: n/a
• Is FDA regulated: No
• Health authority: Netherlands: Ministry of Health, Welfare and Sport
• Study type: Interventional

Clinical Trial Summary

This study investigates the feasibility and immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination in patients with platinum-resistant ovarian cancer.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. primary completion date: January 2014
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Histological proven epithelial ovarian cancer, peritoneal cavity or fallopian tube cancer (inclusive mucinous or clear cell tumors)

• Tumor over-expressing p53

• Progression of disease or relapse after previous therapy with platinum

• Measurable disease (RECIST 1.1) or elevated CA125 > 2 times the upper limit of normal within 3 months and confirmed

• Age = 18 years

• WHO performance status 0-2

• Adequate bone marrow function: WBC = 3.0 x 109/l, neutrophils = 1.5 x 109/l, platelets = 100 x 109/l

• Adequate liver function: bilirubin = 1.5 x upper limit of normal (UNL) range, ALAT and/or ASAT = 2.5 x UNL, Alkaline Phosphatase =5 x UNL

• Adequate renal function: the calculated creatinine clearance should be = 50 mL/min

• Survival expectation > 3 months

• Patients must be accessible for treatment and follow-up

• Written informed consent according to the local Ethics Committee requirements

Exclusion Criteria:

• Previous malignancy within 5 years, with exception of a history of a previous basal cell carcinoma of the skin or pre-invasive carcinoma of the cervix.

• Serious other diseases as recent myocardial infarction, clinical signs of cardiac failure or clinically significant arrhythmias

• Known hypersensitivity reaction to any of the components of the treatment

• Pregnancy or lactating

• Medical or psychological condition which in the opinion of the investigator would not permit the patient to complete the study or sign meaningful informed consent

Study Design

Allocation: Non-Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Ovarian Neoplasms
• Recurrent Ovarian Cancer

Intervention

Drug:
• Interferon Alfa-2b
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
• Interferon Alfa-2b
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

Biological:
• 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.

Locations

Country	Name	City	State
Netherlands	Leiden University Medical Center	Leiden

Sponsors (2)

Lead Sponsor	Collaborator
Leiden University Medical Center	University Medical Center Groningen

Country where clinical trial is conducted

Netherlands, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination	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.	Before treatment, after 2 months and after 6 months after start therapy	Yes
Secondary	Clinical outcome (response (RECIST 1.1)	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	Before treatment, after 2 months and after 6 months after start therapy	No
Secondary	The effect of this new treatment combination on the immune system	Changes in plasma signature and tumor tissue will be measured	Before treatment, after two months and after 6 months after treatment	No
Secondary	progression free survival		Before treatment, after 2 months and after 6 months after start therapy	No
Secondary	overall survival		Before treatment, after 2 months and after 6 months after start therapy	No