- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01639885
Chemo-immunotherapy (Gemcitabine, Interferon-alpha 2b and p53 SLP) in Patients With Platinum-resistant Ovarian Cancer (CHIP)
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 Overview
Status
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
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
-
Leiden, Netherlands, 2333 ZA
- Leiden University Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
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
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)
|
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
|
1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine
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
Sponsor
Collaborators
Study record dates
Study Major Dates
Study Start
Primary Completion (ACTUAL)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (ESTIMATE)
Study Record Updates
Last Update Posted (ESTIMATE)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Neoplasms by Histologic Type
- Neoplasms
- Urogenital Neoplasms
- Neoplasms by Site
- Carcinoma
- Neoplasms, Glandular and Epithelial
- Genital Neoplasms, Female
- Endocrine System Diseases
- Ovarian Diseases
- Adnexal Diseases
- Gonadal Disorders
- Endocrine Gland Neoplasms
- Ovarian Neoplasms
- Carcinoma, Ovarian Epithelial
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antiviral Agents
- Antineoplastic Agents
- Immunologic Factors
- Interferons
- Interferon-alpha
- Interferon alpha-2
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.
Clinical Trials on Recurrent Ovarian Cancer
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedPseudomyxoma Peritonei | Recurrent Endometrial Carcinoma | Ovarian Sarcoma | Recurrent Uterine Sarcoma | Leydig Cell Tumor | Recurrent Ovarian Epithelial Cancer | Recurrent Primary Peritoneal Cavity Cancer | Ovarian Stromal Cancer | Recurrent Ovarian Germ Cell Tumor | Recurrent Fallopian Tube Cancer | Recurrent... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedRecurrent Ovarian Epithelial Cancer | Recurrent Primary Peritoneal Cavity CancerCanada
-
Dana-Farber Cancer InstituteAstraZenecaTerminatedRecurrent Ovarian Carcinoma | Recurrent Cervical Carcinoma | Recurrent Endometrial Cancer | Metastatic Endometrial Cancer | Metastatic Cervical Cancer | Recurrent Vaginal Cancer | Recurrent Vulvar Cancer | Metastatic Ovarian Cancer | Recurrent Gynecological Cancer | Metastatic Vaginal Cancer | Metastatic...United States
-
ImmunoVaccine Technologies, Inc. (IMV Inc.)Incyte CorporationActive, not recruitingRecurrent Fallopian Tube Cancer | Recurrent Epithelial Ovarian Cancer | Recurrent Peritoneal CancerUnited States, Canada
-
CanariaBio Inc.Veristat, LLCActive, not recruitingPeritoneal Cancer | Recurrent Ovarian Cancer | Recurrent Fallopian Tube Cancer | Recurrent Epithelial Cancer of Ovary | Recurrent Epithelial Ovarian Cancer | Recurrent Carcinoma of Ovary | Adenocarcinoma of OvaryUnited States
-
Fox Chase Cancer CenterNational Cancer Institute (NCI)WithdrawnOvarian Serous Cystadenocarcinoma | Recurrent Ovarian Epithelial Cancer | Recurrent Primary Peritoneal Cavity Cancer | Recurrent Ovarian Germ Cell Tumor | Ovarian Papillary Serous Carcinoma | Recurrent Fallopian Tube CancerUnited States
-
Case Comprehensive Cancer CenterNational Cancer Institute (NCI)CompletedFallopian Tube Cancer | Recurrent Endometrial Carcinoma | Stage IV Ovarian Epithelial Cancer | Stage IV Ovarian Germ Cell Tumor | Ovarian Sarcoma | Recurrent Uterine Sarcoma | Stage III Uterine Sarcoma | Stage IV Uterine Sarcoma | Recurrent Ovarian Epithelial Cancer | Stage IV Endometrial Carcinoma | Ovarian... and other conditionsUnited States
-
National Cancer Institute (NCI)CompletedStage IV Ovarian Epithelial Cancer | Recurrent Ovarian Epithelial Cancer | Recurrent Cervical Cancer | Recurrent Vaginal Cancer | Recurrent Vulvar Cancer | Stage III Vaginal Cancer | Stage IVA Cervical Cancer | Stage IVA Vaginal Cancer | Stage IVB Cervical Cancer | Stage IVB Vaginal Cancer | Stage IIIA Ovarian... and other conditionsUnited States
-
University of MiamiWithdrawnOvarian Cancer | Recurrent Ovarian Carcinoma | Ovarian Carcinoma | Recurrent Ovarian Cancer
-
Roswell Park Cancer InstituteEisai Inc.CompletedRecurrent Ovarian Epithelial Cancer | Recurrent Primary Peritoneal Cavity Cancer | Recurrent Fallopian Tube CancerUnited States
Clinical Trials on Interferon Alfa-2b
-
Merck Sharp & Dohme LLCTerminated
-
Roswell Park Cancer InstituteNational Cancer Institute (NCI)SuspendedHematopoietic and Lymphoid Cell Neoplasm | Malignant Solid Neoplasm | Symptomatic COVID-19 Infection Laboratory-ConfirmedUnited States
-
Brooke Army Medical CenterT.R.U.E. Research FoundationCompleted
-
St. Jude Children's Research HospitalSchering-PloughActive, not recruitingMalignant MelanomaUnited States
-
Columbia UniversityMerck Sharp & Dohme LLCWithdrawnEnd Stage Renal Disease | Hepatitis C Infection
-
Amsterdam UMC, location VUmcMerck Sharp & Dohme LLC; Novartis; Uppsala University HospitalTerminatedChronic Myeloid LeukemiaNetherlands, Denmark, Sweden, Finland, Norway
-
Mayo ClinicNational Cancer Institute (NCI)Active, not recruitingPrimary Myelofibrosis | Secondary MyelofibrosisUnited States
-
Eastern Cooperative Oncology GroupNational Cancer Institute (NCI)Completed
-
Merck Sharp & Dohme LLCTerminated
-
Emory UniversityCURE Childhood Cancer, Inc.CompletedJuvenile Pilocytic Astrocytomas | Optic Pathway GliomasUnited States