Recurrent Ovarian CancerPhase 1/2CHIPNCT01639885
Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer
A Phase 1/2 study testing Interferon Alfa-2b and p53 SLP in people with Recurrent Ovarian Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Recurrent Ovarian Cancer
- What is being tested?
- Interferon Alfa-2b and p53 SLP
- Type of treatment
- Vaccines, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 15 participants
- Where
- 1 siteNetherlands
- Study dates
- Aug 2011to Jan 2014
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Show all 12Show fewer
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
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.
Read the 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
- Being tested
- Interferon Alfa-2b, p53 SLP
- Keywords
- p53 overexpression, platinum-resistant
- Medical subject headings
- Ovarian Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Interferon Alfa-2bDrug
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
Interferon Alfa-2bDrug
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
p53 SLPBiological
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.
| Study group | Role | What they receive |
|---|---|---|
| Group 1 | No intervention | Patients will receive standard care (gemcitabine) |
| Group 2 | Experimental | Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) Receives: Drug: Interferon Alfa-2b |
| Group 3 | Experimental | Patients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin Receives: Drug: Interferon Alfa-2b; Biological: p53 SLP |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Before treatment, after 2 months and after 6 months after start therapy
Secondary outcomes (4)
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
Measured: Before treatment, after 2 months and after 6 months after start therapy
The effect of this new treatment combination on the immune system
Changes in plasma signature and tumor tissue will be measured
Measured: Before treatment, after two months and after 6 months after treatment
progression free survival
Measured: Before treatment, after 2 months and after 6 months after start therapy
overall survival
Measured: Before treatment, after 2 months and after 6 months after start therapy
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jul 2012 (estimated)
- Study startAug 2011
- Primary completionJan 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Recurrent Ovarian CancerStudies of the same condition, open and under way.
- More trials run by Leiden University Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 15 participants (actual)
Sponsor and investigators
- Lead sponsor
- Leiden University Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- University Medical Center Groningen
- Responsible party
- Principal investigator, J.R. Kroep, Leiden University Medical Center
- Investigators
- Judith R Kroep, MD, PhD, Principal investigator, Leiden University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01639885
- Sponsor's protocol ID
- CHIP trial
- Other IDs
- 2010-023124-24
- Acronym
- CHIP
- Status last verified
- Jan 2014
- First submitted
- 16 Apr 2012
- Last updated
- 7 Jan 2014
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- 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
- ClinicalTrials.gov ID
- NCT01639885
- Acronym / sponsor ID
- CHIP / CHIP trial
- Conditions
- Recurrent Ovarian Cancer
- Keywords
- p53 overexpression, platinum-resistant
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 15 participants (actual)
- Lead sponsor
- Leiden University Medical CenterUniversity, hospital or other
- Collaborators
- University Medical Center Groningen
- Study start
- Aug 2011
- Primary completion
- Jan 2014 (actual)
- First posted
- 13 Jul 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Group 1 | No intervention | –Patients will receive standard care (gemcitabine) |
| Group 2 | Experimental | Drug: Interferon Alfa-2bPatients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) |
| Group 3 | Experimental | Drug: Interferon Alfa-2b, Biological: p53 SLPPatients will receive standard care (gemcitabine) combined with interferon-alpha 2b (Peg-Intron) and p53 SLP vaccin |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Interferon Alfa-2b1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine | Drug | Group 2 |
| Interferon Alfa-2b1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine | Drug | Group 3 |
| p53 SLP8.2.3 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. | Biological | Group 3 |
Primary outcome
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.
4 secondary outcomes
Clinical outcome (response (RECIST 1.1)
Time frame: 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
progression free survival
Time frame: 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
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2014.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Judith R Kroep, MD, PhD principal investigator
Leiden University Medical Center
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Interferon Alfa-2b and p53 SLP in people with Recurrent Ovarian Cancer, run by Leiden University Medical Center at 1 site in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 7 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 7 Jan 2014.