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

NCT01639885 | Completed Phase 1 DMC

• 2 other identifiers: CHIP trial2010-023124-24
• Study Type: interventional
• Target: 15
• Locations: 1 country
• Sites: 1

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.

Conditions

Recurrent Ovarian Cancer

Keywords

p53 overexpression; platinum-resistant

Outcome Measures

Primary Outcomes (1)

• 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.

  Before treatment, after 2 months and after 6 months after start therapy

Secondary Outcomes (4)

• Clinical outcome (response (RECIST 1.1)

  Before treatment, after 2 months and after 6 months after start therapy

• The effect of this new treatment combination on the immune system

  Before treatment, after two months and after 6 months after treatment

• progression free survival

  Before treatment, after 2 months and after 6 months after start therapy

• overall survival

  Before treatment, after 2 months and after 6 months after start therapy

Study Arms (3)

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)

Drug: Interferon Alfa-2b

Group 3

EXPERIMENTAL

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

Drug: Interferon Alfa-2b; Biological: p53 SLP

Interventions

Interferon Alfa-2b DRUG

1ug/kg (max 100ug) 7 days before and 22 days after first treatment with gemcitabine

Group 2

p53 SLP BIOLOGICAL

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.

Group 3

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Leiden University Medical Center: lead
• University Medical Center Groningen: collaborator

Study Sites (1)

Leiden University Medical Center

Leiden, 2333 ZA, Netherlands

Location

MeSH Terms

Conditions

Ovarian Neoplasms

Interventions

Interferon alpha-2; p53 synthetic long peptide vaccine

Condition Hierarchy (Ancestors)

Endocrine Gland Neoplasms; Neoplasms by Site; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Neoplasms, Female; Urogenital Neoplasms; Genital Diseases; Endocrine System Diseases; Gonadal Disorders

Intervention Hierarchy (Ancestors)

Interferon-alpha; Interferon Type I; Interferons; Cytokines; Intercellular Signaling Peptides and Proteins; Peptides; Amino Acids, Peptides, and Proteins; Proteins; Biological Factors

Study Officials

• Judith R Kroep, MD, PhD

  Leiden University Medical Center

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: MD phD

Study Record Dates

• First Submitted: April 16, 2012
• First Posted: July 13, 2012
• Study Start: August 1, 2011
• Primary Completion: January 1, 2014
• Last Updated: January 7, 2014

Record last verified: 2014-01

Locations

NL (1)