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
  Purpose

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.


Condition Intervention Phase
Recurrent Ovarian Cancer
Drug: Interferon Alfa-2b
Biological: p53 SLP
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Non-Randomized
Endpoint Classification: Safety/Efficacy Study
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

Resource links provided by NLM:


Further study details as provided by Leiden University Medical Center:

Primary Outcome Measures:
  • 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.


Secondary Outcome Measures:
  • 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 ]

Enrollment: 15
Study Start Date: August 2011
Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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 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.

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01639885

Locations
Netherlands
Leiden University Medical Center
Leiden, Netherlands, 2333 ZA
Sponsors and Collaborators
Leiden University Medical Center
University Medical Centre Groningen
Investigators
Principal Investigator: Judith R Kroep, MD, PhD Leiden University Medical Center
  More Information

No publications provided

Responsible Party: J.R. Kroep, MD phD, Leiden University Medical Center
ClinicalTrials.gov Identifier: NCT01639885     History of Changes
Other Study ID Numbers: CHIP trial, 2010-023124-24
Study First Received: April 16, 2012
Last Updated: January 6, 2014
Health Authority: Netherlands: Ministry of Health, Welfare and Sport

Keywords provided by Leiden University Medical Center:
p53 overexpression
platinum-resistant

Additional relevant MeSH terms:
Ovarian Neoplasms
Endocrine Gland Neoplasms
Neoplasms by Site
Neoplasms
Ovarian Diseases
Adnexal Diseases
Genital Diseases, Female
Genital Neoplasms, Female
Urogenital Neoplasms
Endocrine System Diseases
Gonadal Disorders
Interferon-alpha
Interferons
Gemcitabine
Peginterferon alfa-2b
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Immunologic Factors
Physiological Effects of Drugs
Antineoplastic Agents
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Enzyme Inhibitors
Immunosuppressive Agents
Radiation-Sensitizing Agents

ClinicalTrials.gov processed this record on August 18, 2014