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

NCT ID: NCT01639885

Last Updated: 2014-01-07

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 15 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2011-08-31

Brief 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.

Detailed 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.

Conditions

Recurrent Ovarian Cancer

Study Design

• Allocation Method: NON_RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Group 1

Patients will receive standard care (gemcitabine)

Group Type: NO_INTERVENTION

No interventions assigned to this group

Group 2

Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron)

Group Type: EXPERIMENTAL

Interferon Alfa-2b

Intervention Type: DRUG

1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

Group 3

Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin

Group Type: EXPERIMENTAL

Interferon Alfa-2b

Intervention Type: DRUG

1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

p53 SLP

Intervention Type: BIOLOGICAL

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.

Interventions

Interferon Alfa-2b

1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

Intervention Type: DRUG

Interferon Alfa-2b

1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

Intervention Type: DRUG

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.

Intervention Type: BIOLOGICAL

Eligibility Criteria

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

• Minimum Eligible Age: 18 Years
• Eligible Sex: FEMALE
• Accepts Healthy Volunteers: No

Sponsors

University Medical Center Groningen

OTHER

Sponsor Role: collaborator

Leiden University Medical Center

OTHER

Sponsor Role: lead

Responsible Party

J.R. Kroep

MD phD

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Judith R Kroep, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Leiden University Medical Center

Locations

Leiden University Medical Center

Leiden, , Netherlands

Countries

Netherlands

Other Identifiers

2010-023124-24

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

CHIP trial

Identifier Type: -

Identifier Source: org_study_id