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

This study has been completed.
Sponsor:
Collaborator:
University Medical Centre Groningen
Information provided by (Responsible Party):
J.R. Kroep, Leiden University Medical Center
ClinicalTrials.gov Identifier:
NCT01639885
First received: April 16, 2012
Last updated: January 6, 2014
Last verified: January 2014

April 16, 2012
January 6, 2014
August 2011
January 2014   (final data collection date for primary outcome measure)
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 ] [ Designated as safety issue: Yes ]
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.
Same as current
Complete list of historical versions of study NCT01639885 on ClinicalTrials.gov Archive Site
  • Clinical outcome (response (RECIST 1.1) [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
    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 ] [ Designated as safety issue: No ]
  • overall survival [ Time Frame: Before treatment, after 2 months and after 6 months after start therapy ] [ Designated as safety issue: No ]
Same as current
Not Provided
Not Provided
 
Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer
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

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.

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.

Interventional
Phase 1
Phase 2
Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Recurrent Ovarian Cancer
  • Drug: 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.
  • 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)
    Intervention: Drug: Interferon Alfa-2b
  • Experimental: Group 3
    Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin
    Interventions:
    • Drug: Interferon Alfa-2b
    • Biological: p53 SLP
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Completed
15
Not Provided
January 2014   (final data collection date for primary outcome measure)

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
Female
18 Years and older
No
Contact information is only displayed when the study is recruiting subjects
Netherlands
 
NCT01639885
CHIP trial, 2010-023124-24
Yes
J.R. Kroep, Leiden University Medical Center
Leiden University Medical Center
University Medical Centre Groningen
Principal Investigator: Judith R Kroep, MD, PhD Leiden University Medical Center
Leiden University Medical Center
January 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP