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

Primary Purpose

Recurrent Ovarian Cancer

Status
Completed
Phase
Phase 1
Locations
Netherlands
Study Type
Interventional
Intervention
Interferon Alfa-2b
Interferon Alfa-2b
p53 SLP
Sponsored by
Leiden University Medical Center
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Recurrent Ovarian Cancer focused on measuring p53 overexpression, platinum-resistant

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Leiden University Medical Center

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm Type

No Intervention

Experimental

Experimental

Arm Label

Group 1

Group 2

Group 3

Arm Description

Patients will receive standard care (gemcitabine)

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

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

Outcomes

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
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)
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
Changes in plasma signature and tumor tissue will be measured
progression free survival
overall survival

Full Information

First Posted
April 16, 2012
Last Updated
January 6, 2014
Sponsor
Leiden University Medical Center
Collaborators
University Medical Center Groningen
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1. Study Identification

Unique Protocol Identification Number
NCT01639885
Brief Title
Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
January 2014
Overall Recruitment Status
Completed
Study Start Date
August 2011 (undefined)
Primary Completion Date
January 2014 (Actual)
Study Completion Date
undefined (undefined)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Leiden University Medical Center
Collaborators
University Medical Center Groningen

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Recurrent Ovarian Cancer
Keywords
p53 overexpression, platinum-resistant

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
15 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Group 1
Arm Type
No Intervention
Arm Description
Patients will receive standard care (gemcitabine)
Arm Title
Group 2
Arm Type
Experimental
Arm Description
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron)
Arm Title
Group 3
Arm Type
Experimental
Arm Description
Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin
Intervention Type
Drug
Intervention Name(s)
Interferon Alfa-2b
Intervention Description
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
Intervention Type
Drug
Intervention Name(s)
Interferon Alfa-2b
Intervention Description
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
Intervention Type
Biological
Intervention Name(s)
p53 SLP
Intervention Description
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.
Primary Outcome Measure Information:
Title
Feasibility (change in grade III and IV toxicity) and change in immunogenicity of the triple combination of gemcitabine, Peg-Intron and p53 SLP vaccination
Description
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.
Time Frame
Before treatment, after 2 months and after 6 months after start therapy
Secondary Outcome Measure Information:
Title
Clinical outcome (response (RECIST 1.1)
Description
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
Time Frame
Before treatment, after 2 months and after 6 months after start therapy
Title
The effect of this new treatment combination on the immune system
Description
Changes in plasma signature and tumor tissue will be measured
Time Frame
Before treatment, after two months and after 6 months after treatment
Title
progression free survival
Time Frame
Before treatment, after 2 months and after 6 months after start therapy
Title
overall survival
Time Frame
Before treatment, after 2 months and after 6 months after start therapy

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Judith R Kroep, MD, PhD
Organizational Affiliation
Leiden University Medical Center
Official's Role
Principal Investigator
Facility Information:
Facility Name
Leiden University Medical Center
City
Leiden
ZIP/Postal Code
2333 ZA
Country
Netherlands

12. IPD Sharing Statement

Learn more about this trial

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

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