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

January 6, 2014 updated by: J.R. Kroep, Leiden University Medical Center

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.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

15

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Netherlands
      • Leiden, Netherlands, 2333 ZA
        • Leiden University Medical Center

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

Female

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: TREATMENT
  • Allocation: NON_RANDOMIZED
  • Interventional Model: PARALLEL
  • Masking: NONE

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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.
Before treatment, after 2 months and after 6 months after start therapy

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Before treatment, after 2 months and after 6 months after start therapy
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
Before treatment, after two months and after 6 months after treatment
progression free survival
Time Frame: Before treatment, after 2 months and after 6 months after start therapy
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
Before treatment, after 2 months and after 6 months after start therapy

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Leiden University Medical Center

Collaborators

University Medical Center Groningen

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

August 1, 2011

Primary Completion (ACTUAL)

January 1, 2014

Study Registration Dates

First Submitted

April 16, 2012

First Submitted That Met QC Criteria

July 12, 2012

First Posted (ESTIMATE)

July 13, 2012

Study Record Updates

Last Update Posted (ESTIMATE)

January 7, 2014

Last Update Submitted That Met QC Criteria

January 6, 2014

Last Verified

January 1, 2014

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • CHIP trial
  • 2010-023124-24 (EUDRACT_NUMBER)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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